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CDC issues COVID-19 vaccine guidance for underlying conditions
The Centers for Disease Control and Prevention has issued updated guidance for people with underlying medical conditions who are considering getting the coronavirus vaccine.
“Adults of any age with certain underlying medical conditions are at increased risk for severe illness from the virus that causes COVID-19,” the CDC said in the guidance, posted on Dec. 26. “mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine.”
Both the Pfizer and Moderna vaccines use mRNA, or messenger RNA.
The CDC guidance had specific information for people with HIV, weakened immune systems, and autoimmune conditions such as Guillain-Barré syndrome (GBS) and Bell’s palsy who are thinking of getting the vaccine.
People with HIV and weakened immune systems “may receive a COVID-19 vaccine. However, they should be aware of the limited safety data,” the CDC said.
There’s no information available yet about the safety of the vaccines for people with weakened immune systems. People with HIV were included in clinical trials, but “safety data specific to this group are not yet available at this time,” the CDC said.
Cases of Bell’s palsy, a temporary facial paralysis, were reported in people receiving the Pfizer and Moderna vaccines in clinical trials, the Food and Drug Administration said Dec. 17.
But the new CDC guidance said that the FDA “does not consider these to be above the rate expected in the general population. They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell’s palsy may receive an mRNA COVID-19 vaccine.”
Researchers have determined the vaccines are safe for people with GBS, a rare autoimmune disorder in which the body’s immune system attacks nerves just as they leave the spinal cord, the CDC said.
“To date, no cases of GBS have been reported following vaccination among participants in the mRNA COVID-19 vaccine clinical trials,” the CDC guidance said. “With few exceptions, the independent Advisory Committee on Immunization Practices general best practice guidelines for immunization do not include a history of GBS as a precaution to vaccination with other vaccines.”
For months, the CDC and other health authorities have said that people with certain medical conditions are at an increased risk of developing severe cases of COVID-19.
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention has issued updated guidance for people with underlying medical conditions who are considering getting the coronavirus vaccine.
“Adults of any age with certain underlying medical conditions are at increased risk for severe illness from the virus that causes COVID-19,” the CDC said in the guidance, posted on Dec. 26. “mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine.”
Both the Pfizer and Moderna vaccines use mRNA, or messenger RNA.
The CDC guidance had specific information for people with HIV, weakened immune systems, and autoimmune conditions such as Guillain-Barré syndrome (GBS) and Bell’s palsy who are thinking of getting the vaccine.
People with HIV and weakened immune systems “may receive a COVID-19 vaccine. However, they should be aware of the limited safety data,” the CDC said.
There’s no information available yet about the safety of the vaccines for people with weakened immune systems. People with HIV were included in clinical trials, but “safety data specific to this group are not yet available at this time,” the CDC said.
Cases of Bell’s palsy, a temporary facial paralysis, were reported in people receiving the Pfizer and Moderna vaccines in clinical trials, the Food and Drug Administration said Dec. 17.
But the new CDC guidance said that the FDA “does not consider these to be above the rate expected in the general population. They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell’s palsy may receive an mRNA COVID-19 vaccine.”
Researchers have determined the vaccines are safe for people with GBS, a rare autoimmune disorder in which the body’s immune system attacks nerves just as they leave the spinal cord, the CDC said.
“To date, no cases of GBS have been reported following vaccination among participants in the mRNA COVID-19 vaccine clinical trials,” the CDC guidance said. “With few exceptions, the independent Advisory Committee on Immunization Practices general best practice guidelines for immunization do not include a history of GBS as a precaution to vaccination with other vaccines.”
For months, the CDC and other health authorities have said that people with certain medical conditions are at an increased risk of developing severe cases of COVID-19.
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention has issued updated guidance for people with underlying medical conditions who are considering getting the coronavirus vaccine.
“Adults of any age with certain underlying medical conditions are at increased risk for severe illness from the virus that causes COVID-19,” the CDC said in the guidance, posted on Dec. 26. “mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine.”
Both the Pfizer and Moderna vaccines use mRNA, or messenger RNA.
The CDC guidance had specific information for people with HIV, weakened immune systems, and autoimmune conditions such as Guillain-Barré syndrome (GBS) and Bell’s palsy who are thinking of getting the vaccine.
People with HIV and weakened immune systems “may receive a COVID-19 vaccine. However, they should be aware of the limited safety data,” the CDC said.
There’s no information available yet about the safety of the vaccines for people with weakened immune systems. People with HIV were included in clinical trials, but “safety data specific to this group are not yet available at this time,” the CDC said.
Cases of Bell’s palsy, a temporary facial paralysis, were reported in people receiving the Pfizer and Moderna vaccines in clinical trials, the Food and Drug Administration said Dec. 17.
But the new CDC guidance said that the FDA “does not consider these to be above the rate expected in the general population. They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell’s palsy may receive an mRNA COVID-19 vaccine.”
Researchers have determined the vaccines are safe for people with GBS, a rare autoimmune disorder in which the body’s immune system attacks nerves just as they leave the spinal cord, the CDC said.
“To date, no cases of GBS have been reported following vaccination among participants in the mRNA COVID-19 vaccine clinical trials,” the CDC guidance said. “With few exceptions, the independent Advisory Committee on Immunization Practices general best practice guidelines for immunization do not include a history of GBS as a precaution to vaccination with other vaccines.”
For months, the CDC and other health authorities have said that people with certain medical conditions are at an increased risk of developing severe cases of COVID-19.
A version of this article first appeared on Medscape.com.
HPV vaccine appears effective for treating warts, particularly in children
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
FROM COASTAL DERM
Getting closer to a lifesaving RSV vaccine
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
FROM ESPID 2020
Pregnant women should be offered COVID-19 vaccine, experts agree
according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.
Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.
“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.
In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.
Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.
Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.
“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
Acknowledging side effects and uncertainty
ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.”
In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days.
Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.
When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
More data expected
Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study.
Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.
The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.
In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”
“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.
A version of this article first appeared on Medscape.com.
according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.
Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.
“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.
In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.
Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.
Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.
“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
Acknowledging side effects and uncertainty
ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.”
In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days.
Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.
When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
More data expected
Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study.
Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.
The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.
In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”
“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.
A version of this article first appeared on Medscape.com.
according to guidance from the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine.
Pregnant women who opt not to receive the vaccine should be supported in that decision as well, a practice advisory from ACOG recommends.
“Pregnant women who experience fever following vaccination should be counseled to take acetaminophen,” the advisory notes.
In addition, women do not need to avoid pregnancy after receiving the Pfizer-BioNTech COVID-19 vaccine, according to the CDC’s interim clinical considerations for its use. The U.S. Food and Drug Administration issued an emergency use authorization for the vaccine on Dec. 11.
Although investigators excluded pregnant women from clinical trials, experts believe that mRNA vaccines, which are not live vaccines, “are unlikely to pose a risk for people who are pregnant” and “are not thought to be a risk to the breastfeeding infant,” the CDC notes.
Meanwhile, women who are pregnant may be at greater risk of severe COVID-19, even though the absolute risk of severe illness is low. COVID-19 also may increase the risk of adverse pregnancy outcomes, such as preterm birth, although the data have been mixed with some studies finding an association and others not.
“If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., health care personnel), they may choose to be vaccinated,” the CDC advises. “A conversation between the patient and their clinical team may assist with decisions regarding the use of vaccines approved under EUA for the prevention of COVID-19. While a conversation with a health care provider may be helpful, it is not required prior to vaccination.”
Acknowledging side effects and uncertainty
ACOG’s advisory reiterates that approach. The group notes that, based on the mRNA vaccine’s mechanism of action and its safety and efficacy in clinical trials, “it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals ... That said, there are no safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown.”
In clinical trials, most participants experienced mild influenza-like symptoms following vaccination, including injection site reactions, fatigue, chills, muscle and joint pain, and headache. Among participants aged 18-55 years, fever greater than 38°C occurred in 3.7% of participants after the first dose and in 15.8% after the second dose. Most symptoms resolved within a few days.
Women who are pregnant should treat fever with acetaminophen because “fever has been associated with adverse pregnancy outcomes,” according to the ACOG guidance. “Acetaminophen has been proven to be safe for use in pregnancy and does not appear to impact antibody response to COVID-19 vaccines.” Patients may treat other vaccine side effects, such as injection-site soreness with acetaminophen as well.
When counseling patients, clinicians should explain that side effects are a normal part of developing antibodies to protect against COVID-19. “Regardless of their decision,” the group says, “these conversations provide an opportunity to remind patients about the importance of other prevention measures such as hand washing, physical distancing, and wearing a mask.”
More data expected
Data from developmental and reproductive toxicity studies in animals are expected soon, the CDC said. In addition, the manufacturer is following clinical trial participants who became pregnant during the study.
Women who are pregnant and their physicians should weigh factors such as the extent of COVID-19 transmission in the community, the patient’s risk of contracting COVID-19, risks of COVID-19 to the patient and fetus, vaccine efficacy and side effects, and the lack of data about COVID-19 vaccination during pregnancy.
The Society for Maternal-Fetal Medicine recommends that pregnant and lactating women have access to COVID-19 vaccines in general and has advocated for the inclusion of women who are pregnant or lactating in vaccine trials. The society has suggested that health care professionals “counsel their patients that the theoretical risk of fetal harm from mRNA vaccines is very low.” It published resources this week for physicians and patients focused on COVID-19 vaccination and pregnancy.
In a review published online Dec. 10 in the American Journal of Obstetrics & Gynecology MFM, Amanda M. Craig, MD, of Duke University Health System in Durham, N.C., and coauthors note that there “is a theoretical risk for fetal harm from any untested medical intervention and this is no different for COVID-19 vaccines.”
“Pregnant individuals should be given the opportunity, along with their obstetric provider, to weigh the potential risk of severe maternal disease against the unknown risk of fetal exposure, and make an autonomous decision about whether or not to accept vaccine until pregnancy safety data are available,” they write.
A version of this article first appeared on Medscape.com.
Seeking new vaccines against whooping cough: The PERISCOPE project
Although there is an effective vaccine against Bordetella pertussis, whooping cough remains a leading cause of death. Cases are increasing, and scientists face challenges in developing new vaccines.
In a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year, Dimitri Diavatopoulos, PhD, associate professor at the Radboud University Medical Centre Nijmegen, the Netherlands, summarized the pertussis vaccination problem and what the Pertussis Correlates of Protection Europe (PERISCOPE) project seeks to achieve. Dr. Diavatopoulos has a longstanding interest in pertussis and immunity and will soon take over as the scientific coordinator of PERISCOPE.
Pertussis is a highly contagious infectious disease that causes uncontrollable coughing. The disease begins with an atypical cough and rhinorrhea before entering a paroxysmal stage characterized by cyanosis, lymphocytosis, vomiting, and whoops. Generally, fever is absent and coughing increases at night. Finally, after weeks to months, the patient enters a convalescent stage. The World Health Organization estimates that there are 16 million pertussis cases annually and approximately 195,000 deaths in children. Most cases are caused by Bordetella pertussis and are preventable by vaccination.
In the United States, following the introduction of a national immunization program using a whole-cell vaccine in the 1950s, cases fell significantly. After a lag phase, the adoption of an acellular vaccine in the United States in 1997 and the Netherlands in 2005 – usually in combination with diphtheria and tetanus via DTaP – saw an increase in case numbers. Dr. Diavatopoulos stated that control is no longer as good, compared with other infectious diseases prevented by the MMR vaccine, such as mumps, measles, and rubella.
In the face of increasing numbers, how do we move to the next generation of vaccines to improve control? There are several barriers to licensure, including the following:
• Universal recommendation for pertussis prevention means that more than 90% of the population will have received DTaP (usually in combination with polio and Haemophilus influenzae B) and be protected for several years after vaccination.
• Because DTaP vaccines are only efficacious for a limited time, the problem is not immediately apparent.
• Pertussis epidemics are cyclical, occurring every 3-5 years. These peaks and troughs complicate the development of epidemiological studies.
What this means is that large-scale Phase III efficacy studies, in which disease is used as the endpoint, are not feasible. Also, formal correlates of protection have not been identified.
The PERISCOPE Project started in March 2016 and is designed to respond to some of these issues. Funding is made available by a public private consortium involving the Bill & Melinda Gates foundation, the European Union, and European Federation of Pharmaceutical Industries and Associations (EFPIA) partners, and in this case, GlaxoSmithKline and Sanofi Pasteur. In total, there are 22 partners in this project.
The strategic objectives of this partnership include the following:
• Foster expertise and increase capacity in Europe to evaluate new pertussis vaccines both in clinical and preclinical models.
• Identify early biomarkers of long-lasting protective immunity to pertussis in humans. (This step will accelerate and de-risk clinical development of next generation pertussis vaccines.)
• Investigate the impact of maternal vaccination on infant response to pertussis vaccination.
The problem is that there is no one single study design that addresses all questions about the pertussis vaccine. For example, in PERISCOPE, the results of preclinical studies using the baboon or mouse models and addressing disease and colonization endpoints or immunogenicity do not perfectly model human infection and disease.
By comparison, controlled human infection studies provide information on colonization but not disease endpoints. Such studies, however, do provide information on immunogenicity endpoints. Also available are booster vaccination studies and infant vaccination studies providing data on immunogenicity, as well as safety information.
Finally, there are patient studies, such as household contact studies where immunogenicity can be correlated to disease endpoints. From these studies, it will be seen that what is needed is integration of evidence from clinical and preclinical studies to support a new vaccine registration.
PERISCOPE addresses these issues by developing novel, functional antibody and cellular assays and employing cutting-edge methods to characterize innate immune responses and cell-mediated systemic and mucosal immunity. PERISCOPE combines two major industrial partners with public researchers from academic and public health institutes and small and medium-sized enterprises with expertise in clinical trials, vaccinology, immunology, molecular microbiology, challenge models, and bioinformatics.
Andrew Gorringe, PhD, from Public Health England and the Research and Development Institute at Porton Down, Wiltshire, England, said, “Vaccines have greatly reduced the incidence of pertussis, but it remains the most prevalent ‘vaccine preventable’ disease. This is an exciting period for pertussis vaccine research as we find new ways to understand the immunity that protects from both infection and disease. The PERISCOPE project provides a collaborative environment that combines expertise across Europe to provide a route to the development of new, more effective vaccines.”
GSK and Sanofi Pasteur have cofunded the PERISCOPE Project. Dr. Diavatopoulos made no other financial disclosures.
Although there is an effective vaccine against Bordetella pertussis, whooping cough remains a leading cause of death. Cases are increasing, and scientists face challenges in developing new vaccines.
In a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year, Dimitri Diavatopoulos, PhD, associate professor at the Radboud University Medical Centre Nijmegen, the Netherlands, summarized the pertussis vaccination problem and what the Pertussis Correlates of Protection Europe (PERISCOPE) project seeks to achieve. Dr. Diavatopoulos has a longstanding interest in pertussis and immunity and will soon take over as the scientific coordinator of PERISCOPE.
Pertussis is a highly contagious infectious disease that causes uncontrollable coughing. The disease begins with an atypical cough and rhinorrhea before entering a paroxysmal stage characterized by cyanosis, lymphocytosis, vomiting, and whoops. Generally, fever is absent and coughing increases at night. Finally, after weeks to months, the patient enters a convalescent stage. The World Health Organization estimates that there are 16 million pertussis cases annually and approximately 195,000 deaths in children. Most cases are caused by Bordetella pertussis and are preventable by vaccination.
In the United States, following the introduction of a national immunization program using a whole-cell vaccine in the 1950s, cases fell significantly. After a lag phase, the adoption of an acellular vaccine in the United States in 1997 and the Netherlands in 2005 – usually in combination with diphtheria and tetanus via DTaP – saw an increase in case numbers. Dr. Diavatopoulos stated that control is no longer as good, compared with other infectious diseases prevented by the MMR vaccine, such as mumps, measles, and rubella.
In the face of increasing numbers, how do we move to the next generation of vaccines to improve control? There are several barriers to licensure, including the following:
• Universal recommendation for pertussis prevention means that more than 90% of the population will have received DTaP (usually in combination with polio and Haemophilus influenzae B) and be protected for several years after vaccination.
• Because DTaP vaccines are only efficacious for a limited time, the problem is not immediately apparent.
• Pertussis epidemics are cyclical, occurring every 3-5 years. These peaks and troughs complicate the development of epidemiological studies.
What this means is that large-scale Phase III efficacy studies, in which disease is used as the endpoint, are not feasible. Also, formal correlates of protection have not been identified.
The PERISCOPE Project started in March 2016 and is designed to respond to some of these issues. Funding is made available by a public private consortium involving the Bill & Melinda Gates foundation, the European Union, and European Federation of Pharmaceutical Industries and Associations (EFPIA) partners, and in this case, GlaxoSmithKline and Sanofi Pasteur. In total, there are 22 partners in this project.
The strategic objectives of this partnership include the following:
• Foster expertise and increase capacity in Europe to evaluate new pertussis vaccines both in clinical and preclinical models.
• Identify early biomarkers of long-lasting protective immunity to pertussis in humans. (This step will accelerate and de-risk clinical development of next generation pertussis vaccines.)
• Investigate the impact of maternal vaccination on infant response to pertussis vaccination.
The problem is that there is no one single study design that addresses all questions about the pertussis vaccine. For example, in PERISCOPE, the results of preclinical studies using the baboon or mouse models and addressing disease and colonization endpoints or immunogenicity do not perfectly model human infection and disease.
By comparison, controlled human infection studies provide information on colonization but not disease endpoints. Such studies, however, do provide information on immunogenicity endpoints. Also available are booster vaccination studies and infant vaccination studies providing data on immunogenicity, as well as safety information.
Finally, there are patient studies, such as household contact studies where immunogenicity can be correlated to disease endpoints. From these studies, it will be seen that what is needed is integration of evidence from clinical and preclinical studies to support a new vaccine registration.
PERISCOPE addresses these issues by developing novel, functional antibody and cellular assays and employing cutting-edge methods to characterize innate immune responses and cell-mediated systemic and mucosal immunity. PERISCOPE combines two major industrial partners with public researchers from academic and public health institutes and small and medium-sized enterprises with expertise in clinical trials, vaccinology, immunology, molecular microbiology, challenge models, and bioinformatics.
Andrew Gorringe, PhD, from Public Health England and the Research and Development Institute at Porton Down, Wiltshire, England, said, “Vaccines have greatly reduced the incidence of pertussis, but it remains the most prevalent ‘vaccine preventable’ disease. This is an exciting period for pertussis vaccine research as we find new ways to understand the immunity that protects from both infection and disease. The PERISCOPE project provides a collaborative environment that combines expertise across Europe to provide a route to the development of new, more effective vaccines.”
GSK and Sanofi Pasteur have cofunded the PERISCOPE Project. Dr. Diavatopoulos made no other financial disclosures.
Although there is an effective vaccine against Bordetella pertussis, whooping cough remains a leading cause of death. Cases are increasing, and scientists face challenges in developing new vaccines.
In a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year, Dimitri Diavatopoulos, PhD, associate professor at the Radboud University Medical Centre Nijmegen, the Netherlands, summarized the pertussis vaccination problem and what the Pertussis Correlates of Protection Europe (PERISCOPE) project seeks to achieve. Dr. Diavatopoulos has a longstanding interest in pertussis and immunity and will soon take over as the scientific coordinator of PERISCOPE.
Pertussis is a highly contagious infectious disease that causes uncontrollable coughing. The disease begins with an atypical cough and rhinorrhea before entering a paroxysmal stage characterized by cyanosis, lymphocytosis, vomiting, and whoops. Generally, fever is absent and coughing increases at night. Finally, after weeks to months, the patient enters a convalescent stage. The World Health Organization estimates that there are 16 million pertussis cases annually and approximately 195,000 deaths in children. Most cases are caused by Bordetella pertussis and are preventable by vaccination.
In the United States, following the introduction of a national immunization program using a whole-cell vaccine in the 1950s, cases fell significantly. After a lag phase, the adoption of an acellular vaccine in the United States in 1997 and the Netherlands in 2005 – usually in combination with diphtheria and tetanus via DTaP – saw an increase in case numbers. Dr. Diavatopoulos stated that control is no longer as good, compared with other infectious diseases prevented by the MMR vaccine, such as mumps, measles, and rubella.
In the face of increasing numbers, how do we move to the next generation of vaccines to improve control? There are several barriers to licensure, including the following:
• Universal recommendation for pertussis prevention means that more than 90% of the population will have received DTaP (usually in combination with polio and Haemophilus influenzae B) and be protected for several years after vaccination.
• Because DTaP vaccines are only efficacious for a limited time, the problem is not immediately apparent.
• Pertussis epidemics are cyclical, occurring every 3-5 years. These peaks and troughs complicate the development of epidemiological studies.
What this means is that large-scale Phase III efficacy studies, in which disease is used as the endpoint, are not feasible. Also, formal correlates of protection have not been identified.
The PERISCOPE Project started in March 2016 and is designed to respond to some of these issues. Funding is made available by a public private consortium involving the Bill & Melinda Gates foundation, the European Union, and European Federation of Pharmaceutical Industries and Associations (EFPIA) partners, and in this case, GlaxoSmithKline and Sanofi Pasteur. In total, there are 22 partners in this project.
The strategic objectives of this partnership include the following:
• Foster expertise and increase capacity in Europe to evaluate new pertussis vaccines both in clinical and preclinical models.
• Identify early biomarkers of long-lasting protective immunity to pertussis in humans. (This step will accelerate and de-risk clinical development of next generation pertussis vaccines.)
• Investigate the impact of maternal vaccination on infant response to pertussis vaccination.
The problem is that there is no one single study design that addresses all questions about the pertussis vaccine. For example, in PERISCOPE, the results of preclinical studies using the baboon or mouse models and addressing disease and colonization endpoints or immunogenicity do not perfectly model human infection and disease.
By comparison, controlled human infection studies provide information on colonization but not disease endpoints. Such studies, however, do provide information on immunogenicity endpoints. Also available are booster vaccination studies and infant vaccination studies providing data on immunogenicity, as well as safety information.
Finally, there are patient studies, such as household contact studies where immunogenicity can be correlated to disease endpoints. From these studies, it will be seen that what is needed is integration of evidence from clinical and preclinical studies to support a new vaccine registration.
PERISCOPE addresses these issues by developing novel, functional antibody and cellular assays and employing cutting-edge methods to characterize innate immune responses and cell-mediated systemic and mucosal immunity. PERISCOPE combines two major industrial partners with public researchers from academic and public health institutes and small and medium-sized enterprises with expertise in clinical trials, vaccinology, immunology, molecular microbiology, challenge models, and bioinformatics.
Andrew Gorringe, PhD, from Public Health England and the Research and Development Institute at Porton Down, Wiltshire, England, said, “Vaccines have greatly reduced the incidence of pertussis, but it remains the most prevalent ‘vaccine preventable’ disease. This is an exciting period for pertussis vaccine research as we find new ways to understand the immunity that protects from both infection and disease. The PERISCOPE project provides a collaborative environment that combines expertise across Europe to provide a route to the development of new, more effective vaccines.”
GSK and Sanofi Pasteur have cofunded the PERISCOPE Project. Dr. Diavatopoulos made no other financial disclosures.
FROM ESPID 2020
Current PERISCOPE vaccine studies: Toward better pertussis prevention?
With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.
Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.
Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.
Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”
The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.
Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:
First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.
By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.
A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.
Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.
To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
Gambia pertussis study
GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.
GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
The AWARE study
AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.
The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
The MIFI
The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
The BERT study
The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.
BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.
Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).
Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.
At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.
Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.
With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.
Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.
Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.
Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”
The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.
Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:
First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.
By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.
A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.
Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.
To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
Gambia pertussis study
GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.
GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
The AWARE study
AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.
The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
The MIFI
The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
The BERT study
The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.
BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.
Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).
Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.
At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.
Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.
With increasing whooping cough numbers, developing an effective new vaccine against Bordetella pertussis is a priority. Results from the multifactorial PERISCOPE Project will help scientists and clinicians move forward.
Dominic Kelly, PhD, talked about vaccine-induced immunity and provided an overview of ongoing clinical trials in the PERISCOPE (Pertussis Correlates of Protection Europe) project in a key research session at the start of the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Dr. Kelly, a pediatrician at the Children’s Hospital in Oxford and a member of the Oxford Vaccines Group, leads one of the studies in the project looking at infant vaccination.
Dr. Kelly began his presentation by showing a figure depicting where vaccine-induced immunity fits into the larger suite of clinical studies. These studies involve mouse models, human challenge models, and infection patients. A key theme is the use of a core group of immunoassays across all studies, with the hope that they will allow effective cross comparisons.
Dr. Kelly stated, “If we find a correlate of protection in the challenge model, we can then interpret the vaccine studies in the light of that because we are using standardized constant immunoassays.”
The assays being used depend in part on the specific study and the volume of blood available. They will generally include Bordetella-specific antibody and functional antibody assays, as well as interesting studies collecting mucosal samples from infants and adults to look at serological responses. Also under examination are a range of enzyme-linked immune absorbent spot, flow cytometry, and culture techniques looking at Memory B cells, T cells, and gene expression.
Complementing these assay studies, PERISCOPE includes a series of clinical investigations designed to throw light on three areas of interest, described below:
First, researchers hope to gain a better understanding regarding the effects of the original whole cell vaccine versus the current acellular variety. The former uses an inactivated version of the whole organism. Epidemiological studies, animal data, and experience in the field demonstrate that whole-cell vaccination results in a broad, long-lasting, and effective immune response.
By comparison, the acellular pertussis vaccine consists of between three and five protein components, which are purified from cultured Bordetella pertussis. While it is an effective vaccine, its effects are less durable; routine use in some countries is associated with cyclical outbreaks of increasing severity.
A second issue for researchers involved in the PERISCOPE project concerns the effects of maternal immunization. In the United Kingdom in 2012, for example, an increasing number of cases were noted 6-7 years after adoption of an acellular vaccine for routine vaccination in the 2nd-3rd trimester of pregnancy. Vaccination appears to effectively control neonatal disease, but whether this influences infant immune responses and long-term control of pertussis for a population is unknown.
Finally, the group is interested in the effects of an acellular booster across all age groups. While the effects may be short-lived, the booster is a potential strategy for controlling a population by repeated boosting of immunity. This is another area where using novel immunoassays may aid better understanding.
To find answers, the consortium has established four studies: the Gambia Pertussis study (GaPs) in Gambia and AWARE, the sister study to GaPs in the United Kingdom, addressing the acellular pertussis versus cellular pertussis question; the Pertussis Maternal Immunization Study in Finland (MIFI) addressing maternal immunization; and the Booster against Pertussis (BERT) study across three countries (U.K., the Netherlands, and Finland) looking at acellular booster across age groups.
Gambia pertussis study
GaPs is the largest single study in the project and is being run at the Medical Research Council–funded London School of Tropical Medicine center in Gambia. Beate Kampmann, MD, PhD, of Imperial College London, England, is the project lead. It is due to complete in 2022. GaPs seeks to enroll 600 mother/infant pairs and randomize the mothers to either an acellular pertussis booster in pregnancy or a tetanus toxoid control vaccine. Infants are subsequently randomized to an acellular or whole-cell pertussis schedule of primary immunization. The vaccine doses are being given at 2, 3, and 4 months. The primary endpoint is a serological finding being measured at 9 months of age, when the infant would usually receive yellow fever, measles, and rubella vaccination.
GaPs has a number of pathways. Within each of the four arms generated by the two randomizations, the maternal randomization and the infant randomization, there are five subgroups. They are designed to study time points in subgroups A and B after the first dose in more detail, looking at the innate immune responses using gene expression. It will enable researchers to study adaptive immune responses to T cells and B cells after the second dose of vaccine. By employing a range of subgroups, the team can explore the immune profile using the assays referred to above. Such information should provide new insights into the differences between acellular and whole-cell vaccines.
The AWARE study
AWARE is the sister study to GaPs and looks at the acellular/whole pertussis issue. Because many developed countries, such as the United Kingdom, have established maternal immunization programs, it is not possible to randomize mothers. Consequently, researchers have opted to recruit infants of mothers who have received an acellular vaccine in pregnancy and randomize them to either an acellular schedule of primary immunization or a whole-cell schedule.
The selected vaccine is ComVac5 from Bharat Biotech. This whole-cell vaccine differs from that used in Gambia. An early obstacle for AWARE has been seeking permission to import a non-conventional vaccine into Europe. It has delayed the anticipated end date to 2023. Participating infants will receive a two-dose schedule at 2 and 4 months of age per their randomization; then, both groups will go on to receive an acellular pertussis booster at 12 months. At all time points, the team will sample blood for cells and serum, as well as mucosal fluid from the nose. Because the mucosal surface is where the action is, this approach will likely generate new data around antibody responses.
The MIFI
The Pertussis Maternal Immunization Study in Finland is being run by Jussi Mertsola, of the University of Turku, Finland, and Qiushui He, of the National Public Health Institute, Turku. It is due to complete in late 2021. Where, in the United Kingdom, researchers are unable to randomize mothers because of the current guidelines, researchers in Finland do not have a maternal immunization program to consider. MIFI will randomize 80 mothers, 40 to immunization with acellular pertussis and 40 to a control group. Dr. Kelly stated that whole cell vaccines are not available for use in Finland. Participants will receive a two-dose schedule at 3 and 5 months. Blood samples will then be taken to compare the serological and cellular responses, which will help researchers understand the effects of maternal immunization. In addition, there will be sampling of mucosal fluid using a device that collects a standardized aliquot of fluid.
The BERT study
The final clinical element of PERISCOPE presented by Dr. Kelly was the Booster against Pertussis study. This study is near completion. It seeks to examine the use of an acellular booster across different age groups and three countries: the United Kingdom, the Netherlands, and Finland. The study is being coordinated by Guy Berbers, PhD, at the National Institute for Public Health and the Environment in the Netherlands.
BERT comprises four cohorts (A, B, C, D) of different ages: 7-10 years (36 participants), 11-15 years (36 participants), mid-adult (25 participants), and older age (25 participants). After receiving an acellular booster, participants will undergo intense sampling. Sampling will take place immediately after immunization at day 7 and look at adaptive effects, then again at day 28 and day 365.
Because some participants will have already received whole cell or acellular vaccination, this approach will allow researchers to look at the effects of priming (i.e., how long the B cell/T cell antibody responses last).
Involving different countries across Europe ensures wide applicability of results, but also allows researchers to compare the effects of very different immunization histories.
At the end of this ESPID session, Dimitri Diavatopoulos, PhD, assistant professor at the Radboud University Medical Centre Nijmegen, the Netherlands, commented that a future problem in studying pertussis vaccines and their potential clinical application is that most vaccination schedules now involve combination products. Obtaining a stand-alone vaccination may prove difficult, and there may be resistance if it complicates current vaccination programs.
Dr. Kelly acknowledged funding for the PERISCOPE project from GlaxoSmithKline and Pasteur Sanofi.
FROM ESPID 2020
COVID-19–induced drop in first measles vaccinations sparks resurgence concerns
Widespread use of the MMR vaccine is not only crucial for protecting the community against infectious outbreaks, but also serves as the overall pacesetter for preventive services, said Sara M. Bode, MD and colleagues at Nationwide Children’s Hospital in Columbus.
As part of a bivariate logistic regression analysis, Dr. Bode and colleagues sought to evaluate changes in measles vaccination rates across 12 clinic sites of the Nationwide Children’s Hospital pediatric primary care network in Columbus among 23,534 children aged 16 months. The study period targeted the time between April and May 2020, when clinic access and appointment attendance declined following the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, until the June-to-August 2020 time period, when clinical care was allowed to return.
The need for the study was prompted by Centers for Disease Control and Prevention reporting on a state-specific precipitous decline in MMR vaccination rates shortly after the onset of COVID-19 in May 2020. Citing the results of one study, such reductions in vaccination have raised concerns over the possibility of a measles resurgence, noted Dr. Bode and associates.
MMR vaccination rates begin to drop with onset of COVID-19 pandemic.
From March 2017 to March 2020, the average rate of MMR vaccination in 16-month-olds was 72%. It subsequently decreased to 67% from April to May 2020, and then dropped further to 62% during the period June to August, 2020 (P = .001). Those without insurance were less likely to be vaccinated than were those carrying private insurance or Medicaid.
Among patients who had not attended a preventive care visit after 12 months of age, the proportion who received vaccines declined during the same time periods, from 10% before the pandemic to 6% at the start of the pandemic and 3% during the summer months of 2020.
“Given the baseline low vaccination rates even before the pandemic and the subsequent decline, we face a critical need to improve timely vaccination and provide catch-up opportunities” in areas with the highest incidence of COVID-19, observed Dr. Bode and colleagues.
Innovative approaches are needed to encourage families to seek preventive care.
In response, the researchers announced the implementation of new community-based vaccination approaches in Ohio, including pop-up vaccine clinics, mobile clinics, and school-based clinics to provide families, who are reluctant to visit health care facilities over COVID-19 related concerns, with safe alternatives. “We believe that it is critical to develop innovative approaches to have families return for preventive care,” they added.
In a separate interview, Herschel Lessin, MD, a private practice pediatrician in Poughkeepsie, N.Y., noted: “This study confirms the anecdotal experience of pediatricians around the country, and our greatest fear that the pandemic will interfere with herd immunity of children for vaccine-preventable illness. Although the study was of urban offices with a primarily Medicaid population, I believe the results to be very worrisome should they prove to be generalizable to the country, as a whole. The significant reduction of well-child visits due to COVID-19 (and fear of COVID-19) seriously impaired the vaccination status of a standard required vaccine in a large population. What is even more worrisome is that the rates continued to fall even after the initial closure of many offices and well into their reopening, despite concerted efforts to try to catch up these missed visits and immunizations.”
Measles is an intensely contagious illness that has not been eradicated, as evidenced by the enormous measles outbreak stemming from Disneyland in 2014-2015, and again with the possible exposure of hundreds to an infected Disneyland visitor last fall, where coverage rates were even higher than in this study, added Dr. Lessin. “This phenomenon, unless forcefully remedied, could easily result in large outbreaks of other vaccine-preventable illness besides COVID-19,” he cautioned.
Dr. Bode and colleagues as well as Dr. Lessin had no conflicts of interest and no relevant financial disclosures.
SOURCE: Bode SM et al. Pediatrics. 2021. doi: 10.1542/peds.2020-035576.
Widespread use of the MMR vaccine is not only crucial for protecting the community against infectious outbreaks, but also serves as the overall pacesetter for preventive services, said Sara M. Bode, MD and colleagues at Nationwide Children’s Hospital in Columbus.
As part of a bivariate logistic regression analysis, Dr. Bode and colleagues sought to evaluate changes in measles vaccination rates across 12 clinic sites of the Nationwide Children’s Hospital pediatric primary care network in Columbus among 23,534 children aged 16 months. The study period targeted the time between April and May 2020, when clinic access and appointment attendance declined following the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, until the June-to-August 2020 time period, when clinical care was allowed to return.
The need for the study was prompted by Centers for Disease Control and Prevention reporting on a state-specific precipitous decline in MMR vaccination rates shortly after the onset of COVID-19 in May 2020. Citing the results of one study, such reductions in vaccination have raised concerns over the possibility of a measles resurgence, noted Dr. Bode and associates.
MMR vaccination rates begin to drop with onset of COVID-19 pandemic.
From March 2017 to March 2020, the average rate of MMR vaccination in 16-month-olds was 72%. It subsequently decreased to 67% from April to May 2020, and then dropped further to 62% during the period June to August, 2020 (P = .001). Those without insurance were less likely to be vaccinated than were those carrying private insurance or Medicaid.
Among patients who had not attended a preventive care visit after 12 months of age, the proportion who received vaccines declined during the same time periods, from 10% before the pandemic to 6% at the start of the pandemic and 3% during the summer months of 2020.
“Given the baseline low vaccination rates even before the pandemic and the subsequent decline, we face a critical need to improve timely vaccination and provide catch-up opportunities” in areas with the highest incidence of COVID-19, observed Dr. Bode and colleagues.
Innovative approaches are needed to encourage families to seek preventive care.
In response, the researchers announced the implementation of new community-based vaccination approaches in Ohio, including pop-up vaccine clinics, mobile clinics, and school-based clinics to provide families, who are reluctant to visit health care facilities over COVID-19 related concerns, with safe alternatives. “We believe that it is critical to develop innovative approaches to have families return for preventive care,” they added.
In a separate interview, Herschel Lessin, MD, a private practice pediatrician in Poughkeepsie, N.Y., noted: “This study confirms the anecdotal experience of pediatricians around the country, and our greatest fear that the pandemic will interfere with herd immunity of children for vaccine-preventable illness. Although the study was of urban offices with a primarily Medicaid population, I believe the results to be very worrisome should they prove to be generalizable to the country, as a whole. The significant reduction of well-child visits due to COVID-19 (and fear of COVID-19) seriously impaired the vaccination status of a standard required vaccine in a large population. What is even more worrisome is that the rates continued to fall even after the initial closure of many offices and well into their reopening, despite concerted efforts to try to catch up these missed visits and immunizations.”
Measles is an intensely contagious illness that has not been eradicated, as evidenced by the enormous measles outbreak stemming from Disneyland in 2014-2015, and again with the possible exposure of hundreds to an infected Disneyland visitor last fall, where coverage rates were even higher than in this study, added Dr. Lessin. “This phenomenon, unless forcefully remedied, could easily result in large outbreaks of other vaccine-preventable illness besides COVID-19,” he cautioned.
Dr. Bode and colleagues as well as Dr. Lessin had no conflicts of interest and no relevant financial disclosures.
SOURCE: Bode SM et al. Pediatrics. 2021. doi: 10.1542/peds.2020-035576.
Widespread use of the MMR vaccine is not only crucial for protecting the community against infectious outbreaks, but also serves as the overall pacesetter for preventive services, said Sara M. Bode, MD and colleagues at Nationwide Children’s Hospital in Columbus.
As part of a bivariate logistic regression analysis, Dr. Bode and colleagues sought to evaluate changes in measles vaccination rates across 12 clinic sites of the Nationwide Children’s Hospital pediatric primary care network in Columbus among 23,534 children aged 16 months. The study period targeted the time between April and May 2020, when clinic access and appointment attendance declined following the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, until the June-to-August 2020 time period, when clinical care was allowed to return.
The need for the study was prompted by Centers for Disease Control and Prevention reporting on a state-specific precipitous decline in MMR vaccination rates shortly after the onset of COVID-19 in May 2020. Citing the results of one study, such reductions in vaccination have raised concerns over the possibility of a measles resurgence, noted Dr. Bode and associates.
MMR vaccination rates begin to drop with onset of COVID-19 pandemic.
From March 2017 to March 2020, the average rate of MMR vaccination in 16-month-olds was 72%. It subsequently decreased to 67% from April to May 2020, and then dropped further to 62% during the period June to August, 2020 (P = .001). Those without insurance were less likely to be vaccinated than were those carrying private insurance or Medicaid.
Among patients who had not attended a preventive care visit after 12 months of age, the proportion who received vaccines declined during the same time periods, from 10% before the pandemic to 6% at the start of the pandemic and 3% during the summer months of 2020.
“Given the baseline low vaccination rates even before the pandemic and the subsequent decline, we face a critical need to improve timely vaccination and provide catch-up opportunities” in areas with the highest incidence of COVID-19, observed Dr. Bode and colleagues.
Innovative approaches are needed to encourage families to seek preventive care.
In response, the researchers announced the implementation of new community-based vaccination approaches in Ohio, including pop-up vaccine clinics, mobile clinics, and school-based clinics to provide families, who are reluctant to visit health care facilities over COVID-19 related concerns, with safe alternatives. “We believe that it is critical to develop innovative approaches to have families return for preventive care,” they added.
In a separate interview, Herschel Lessin, MD, a private practice pediatrician in Poughkeepsie, N.Y., noted: “This study confirms the anecdotal experience of pediatricians around the country, and our greatest fear that the pandemic will interfere with herd immunity of children for vaccine-preventable illness. Although the study was of urban offices with a primarily Medicaid population, I believe the results to be very worrisome should they prove to be generalizable to the country, as a whole. The significant reduction of well-child visits due to COVID-19 (and fear of COVID-19) seriously impaired the vaccination status of a standard required vaccine in a large population. What is even more worrisome is that the rates continued to fall even after the initial closure of many offices and well into their reopening, despite concerted efforts to try to catch up these missed visits and immunizations.”
Measles is an intensely contagious illness that has not been eradicated, as evidenced by the enormous measles outbreak stemming from Disneyland in 2014-2015, and again with the possible exposure of hundreds to an infected Disneyland visitor last fall, where coverage rates were even higher than in this study, added Dr. Lessin. “This phenomenon, unless forcefully remedied, could easily result in large outbreaks of other vaccine-preventable illness besides COVID-19,” he cautioned.
Dr. Bode and colleagues as well as Dr. Lessin had no conflicts of interest and no relevant financial disclosures.
SOURCE: Bode SM et al. Pediatrics. 2021. doi: 10.1542/peds.2020-035576.
FROM PEDIATRICS
CDC identifies next priority groups for COVID-19 vaccine
The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted 13-1 for the recommendation. This builds on ACIP’s initial recommendation about which groups should be in the first wave of vaccinations, described as Phase 1a.
ACIP earlier recommended that Phase 1a include U.S. health care workers, a group of about 21 million people, and residents of long-term care facilities, a group of about 3 million.
On Dec. 20, ACIP said the next priority group, Phase 1b, should consist of what it called frontline essential workers, a group of about 30 million, and adults aged 75 years and older, a group of about 21 million. When overlap between the groups is taken into account, Phase 1b covers about 49 million people, according to the CDC.
Phase 1c then would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in Phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million.
The Food and Drug Administration recently granted emergency use authorizations for two COVID-19 vaccines, one developed by Pfizer-BioNTech and another from Moderna. Other companies, including Johnson & Johnson, have advanced their potential rival COVID-19 vaccines into late-stages of testing. To date, about 2.83 million doses of Pfizer’s COVID-19 vaccine have been distributed and 556,208 doses have been administered, according to the CDC.
But there will likely still be a period of months when competition for limited doses of COVID-19 vaccine will trigger difficult decisions. Current estimates indicate there will be enough supply to provide COVID-19 vaccines for 20 million people in December, 30 million people in January, and 50 million people in February, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases.
State governments and health systems will take ACIP’s recommendations into account as they roll out the initial supplies of COVID-19 vaccines.
There’s clearly wide latitude in these decisions. Recently, for example, many members of Congress tweeted photos of themselves getting COVID-19 vaccines, despite not falling into ACIP’s description of the Phase 1 group.
Difficult choices
All ACIP members described the Dec. 20 vote as a difficult decision. It forced them to choose among segments of the U.S. population that could benefit from early access to the limited supply of COVID-19 vaccines.
“For every group we add, it means we subtract a group. For every group we subtract, it means they don’t get the vaccine” for some months, said ACIP member Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn. “It’s incredibly humbling and heartbreaking.”
ACIP member Henry Bernstein, DO, who cast the lone dissenting vote, said he agreed with most of the panel’s recommendation. He said he fully supported the inclusion of adults aged 75 years and older and essential frontline workers in the second wave, Phase 1b. But he voted no because the data on COVID-19 morbidity and mortality for adults aged 65-74 years is similar enough to the older group to warrant their inclusion in the first wave.
“Therefore, inclusion of the 65- to 74-year-old group in Phase 1b made more sense to me,” said Dr. Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in New York.
As defined by the CDC, frontline essential workers included in phase 1b will be those commonly called “first responders,” such as firefighters and police officers. Also in this group are teachers, support staff, daycare providers, and those employed in grocery and agriculture industries. Others in this group would include U.S. Postal Service employees and transit workers.
ACIP panelists noted the difficulties that will emerge as government officials and leaders of health care organizations move to apply their guidance to real-world decisions about distributing a limited supply of COVID-19 vaccine. There’s a potential to worsen existing disparities in access to health care, as people with more income may find it easier to obtain proof that they qualify as having a high-risk condition, said José Romero, MD, the chair of ACIP.
Many people “don’t have access to medical care and can’t come up with a doctor’s note that says, ‘I have diabetes,’ ” he said.
ACIP panelists also noted in their deliberations that people may technically qualify for a priority group but have little risk, such as someone with a chronic medical condition who works from home.
And the risk for COVID-19 remains serious even for those who will ultimately fall into the phase 2 for vaccination. Young adults have suffered serious complications following COVID-19, such as stroke, that may alter their lives dramatically, ACIP member Dr. Talbot said, adding that she is reminded of this in her work.
“We need to be very cautious about saying, ‘Young adults will be fine,’ ” she said. “I spent the past week on back-up clinical call and have read these charts and have cried every day.”
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines. The other panel members have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted 13-1 for the recommendation. This builds on ACIP’s initial recommendation about which groups should be in the first wave of vaccinations, described as Phase 1a.
ACIP earlier recommended that Phase 1a include U.S. health care workers, a group of about 21 million people, and residents of long-term care facilities, a group of about 3 million.
On Dec. 20, ACIP said the next priority group, Phase 1b, should consist of what it called frontline essential workers, a group of about 30 million, and adults aged 75 years and older, a group of about 21 million. When overlap between the groups is taken into account, Phase 1b covers about 49 million people, according to the CDC.
Phase 1c then would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in Phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million.
The Food and Drug Administration recently granted emergency use authorizations for two COVID-19 vaccines, one developed by Pfizer-BioNTech and another from Moderna. Other companies, including Johnson & Johnson, have advanced their potential rival COVID-19 vaccines into late-stages of testing. To date, about 2.83 million doses of Pfizer’s COVID-19 vaccine have been distributed and 556,208 doses have been administered, according to the CDC.
But there will likely still be a period of months when competition for limited doses of COVID-19 vaccine will trigger difficult decisions. Current estimates indicate there will be enough supply to provide COVID-19 vaccines for 20 million people in December, 30 million people in January, and 50 million people in February, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases.
State governments and health systems will take ACIP’s recommendations into account as they roll out the initial supplies of COVID-19 vaccines.
There’s clearly wide latitude in these decisions. Recently, for example, many members of Congress tweeted photos of themselves getting COVID-19 vaccines, despite not falling into ACIP’s description of the Phase 1 group.
Difficult choices
All ACIP members described the Dec. 20 vote as a difficult decision. It forced them to choose among segments of the U.S. population that could benefit from early access to the limited supply of COVID-19 vaccines.
“For every group we add, it means we subtract a group. For every group we subtract, it means they don’t get the vaccine” for some months, said ACIP member Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn. “It’s incredibly humbling and heartbreaking.”
ACIP member Henry Bernstein, DO, who cast the lone dissenting vote, said he agreed with most of the panel’s recommendation. He said he fully supported the inclusion of adults aged 75 years and older and essential frontline workers in the second wave, Phase 1b. But he voted no because the data on COVID-19 morbidity and mortality for adults aged 65-74 years is similar enough to the older group to warrant their inclusion in the first wave.
“Therefore, inclusion of the 65- to 74-year-old group in Phase 1b made more sense to me,” said Dr. Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in New York.
As defined by the CDC, frontline essential workers included in phase 1b will be those commonly called “first responders,” such as firefighters and police officers. Also in this group are teachers, support staff, daycare providers, and those employed in grocery and agriculture industries. Others in this group would include U.S. Postal Service employees and transit workers.
ACIP panelists noted the difficulties that will emerge as government officials and leaders of health care organizations move to apply their guidance to real-world decisions about distributing a limited supply of COVID-19 vaccine. There’s a potential to worsen existing disparities in access to health care, as people with more income may find it easier to obtain proof that they qualify as having a high-risk condition, said José Romero, MD, the chair of ACIP.
Many people “don’t have access to medical care and can’t come up with a doctor’s note that says, ‘I have diabetes,’ ” he said.
ACIP panelists also noted in their deliberations that people may technically qualify for a priority group but have little risk, such as someone with a chronic medical condition who works from home.
And the risk for COVID-19 remains serious even for those who will ultimately fall into the phase 2 for vaccination. Young adults have suffered serious complications following COVID-19, such as stroke, that may alter their lives dramatically, ACIP member Dr. Talbot said, adding that she is reminded of this in her work.
“We need to be very cautious about saying, ‘Young adults will be fine,’ ” she said. “I spent the past week on back-up clinical call and have read these charts and have cried every day.”
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines. The other panel members have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted 13-1 for the recommendation. This builds on ACIP’s initial recommendation about which groups should be in the first wave of vaccinations, described as Phase 1a.
ACIP earlier recommended that Phase 1a include U.S. health care workers, a group of about 21 million people, and residents of long-term care facilities, a group of about 3 million.
On Dec. 20, ACIP said the next priority group, Phase 1b, should consist of what it called frontline essential workers, a group of about 30 million, and adults aged 75 years and older, a group of about 21 million. When overlap between the groups is taken into account, Phase 1b covers about 49 million people, according to the CDC.
Phase 1c then would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in Phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million.
The Food and Drug Administration recently granted emergency use authorizations for two COVID-19 vaccines, one developed by Pfizer-BioNTech and another from Moderna. Other companies, including Johnson & Johnson, have advanced their potential rival COVID-19 vaccines into late-stages of testing. To date, about 2.83 million doses of Pfizer’s COVID-19 vaccine have been distributed and 556,208 doses have been administered, according to the CDC.
But there will likely still be a period of months when competition for limited doses of COVID-19 vaccine will trigger difficult decisions. Current estimates indicate there will be enough supply to provide COVID-19 vaccines for 20 million people in December, 30 million people in January, and 50 million people in February, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases.
State governments and health systems will take ACIP’s recommendations into account as they roll out the initial supplies of COVID-19 vaccines.
There’s clearly wide latitude in these decisions. Recently, for example, many members of Congress tweeted photos of themselves getting COVID-19 vaccines, despite not falling into ACIP’s description of the Phase 1 group.
Difficult choices
All ACIP members described the Dec. 20 vote as a difficult decision. It forced them to choose among segments of the U.S. population that could benefit from early access to the limited supply of COVID-19 vaccines.
“For every group we add, it means we subtract a group. For every group we subtract, it means they don’t get the vaccine” for some months, said ACIP member Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn. “It’s incredibly humbling and heartbreaking.”
ACIP member Henry Bernstein, DO, who cast the lone dissenting vote, said he agreed with most of the panel’s recommendation. He said he fully supported the inclusion of adults aged 75 years and older and essential frontline workers in the second wave, Phase 1b. But he voted no because the data on COVID-19 morbidity and mortality for adults aged 65-74 years is similar enough to the older group to warrant their inclusion in the first wave.
“Therefore, inclusion of the 65- to 74-year-old group in Phase 1b made more sense to me,” said Dr. Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in New York.
As defined by the CDC, frontline essential workers included in phase 1b will be those commonly called “first responders,” such as firefighters and police officers. Also in this group are teachers, support staff, daycare providers, and those employed in grocery and agriculture industries. Others in this group would include U.S. Postal Service employees and transit workers.
ACIP panelists noted the difficulties that will emerge as government officials and leaders of health care organizations move to apply their guidance to real-world decisions about distributing a limited supply of COVID-19 vaccine. There’s a potential to worsen existing disparities in access to health care, as people with more income may find it easier to obtain proof that they qualify as having a high-risk condition, said José Romero, MD, the chair of ACIP.
Many people “don’t have access to medical care and can’t come up with a doctor’s note that says, ‘I have diabetes,’ ” he said.
ACIP panelists also noted in their deliberations that people may technically qualify for a priority group but have little risk, such as someone with a chronic medical condition who works from home.
And the risk for COVID-19 remains serious even for those who will ultimately fall into the phase 2 for vaccination. Young adults have suffered serious complications following COVID-19, such as stroke, that may alter their lives dramatically, ACIP member Dr. Talbot said, adding that she is reminded of this in her work.
“We need to be very cautious about saying, ‘Young adults will be fine,’ ” she said. “I spent the past week on back-up clinical call and have read these charts and have cried every day.”
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines. The other panel members have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Second COVID-19 vaccine ready for use, CDC panel says
The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.
On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.
Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.
“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.
“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA “represents progress towards ending this horrific pandemic,” she said.
In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.
ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”
Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.
ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.
Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.
There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.
“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”
Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.
V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.
“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.
Anaphylaxis concerns
The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.
Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.
People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.
Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.
“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.
Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.
Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.
“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.
The other panel members have reported no relevant financial relationships.
This article first appeared on Medscape.com.
The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.
On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.
Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.
“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.
“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA “represents progress towards ending this horrific pandemic,” she said.
In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.
ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”
Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.
ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.
Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.
There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.
“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”
Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.
V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.
“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.
Anaphylaxis concerns
The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.
Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.
People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.
Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.
“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.
Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.
Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.
“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.
The other panel members have reported no relevant financial relationships.
This article first appeared on Medscape.com.
The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.
On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.
Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.
“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.
“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA “represents progress towards ending this horrific pandemic,” she said.
In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.
ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”
Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.
ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.
Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.
There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.
“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”
Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.
V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.
“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.
Anaphylaxis concerns
The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.
Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.
People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.
Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.
“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.
Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.
Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.
“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.
The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.
The other panel members have reported no relevant financial relationships.
This article first appeared on Medscape.com.
FDA grants emergency use for Moderna COVID-19 vaccine
As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18.
There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.
The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.
Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).
The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.
Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.
“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”
“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.
Ramping up healthcare provider immunizations
“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.
“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.
The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.
Unanswered questions remain
Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”
Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”
“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.
Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.
Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.
“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”
“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.
During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.
“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.
Advantages beyond the numbers?
“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”
“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”
Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.
In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.
As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.
“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.
She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”
Future outlook
Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”
“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”
“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”
“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”
Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.
“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”
El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.
This article first appeared on Medscape.com.
As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18.
There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.
The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.
Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).
The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.
Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.
“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”
“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.
Ramping up healthcare provider immunizations
“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.
“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.
The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.
Unanswered questions remain
Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”
Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”
“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.
Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.
Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.
“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”
“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.
During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.
“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.
Advantages beyond the numbers?
“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”
“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”
Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.
In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.
As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.
“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.
She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”
Future outlook
Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”
“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”
“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”
“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”
Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.
“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”
El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.
This article first appeared on Medscape.com.
As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18.
There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.
The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.
Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).
The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.
Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.
“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”
“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.
Ramping up healthcare provider immunizations
“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.
“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.
The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.
Unanswered questions remain
Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”
Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”
“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.
Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.
Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.
“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”
“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.
During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.
“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.
Advantages beyond the numbers?
“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”
“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”
Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.
In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.
As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.
“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.
She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”
Future outlook
Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”
“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”
“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”
“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”
Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.
“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”
El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.
This article first appeared on Medscape.com.