Vaccines

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

[email protected]

Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

[email protected]

Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

[email protected]

A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.

A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.

Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.

After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.

“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.

In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.

The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.

However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.

None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.

The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.

“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.

But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.

The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.

SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925

A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.

A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.

Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.

After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.

“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.

In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.

The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.

However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.

None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.

The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.

“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.

But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.

The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.

SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925

A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.

A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.

Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.

After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.

“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.

In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.

The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.

However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.

None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.

The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.

“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.

But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.

The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.

SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925

The Food and Drug Administration has approved Jynneos, a live, nonreplicating vaccine based on the vaccinia virus, for smallpox and monkeypox, becoming the first FDA-approved vaccine for the prevention of monkeypox disease.

FDA approval for Jynneos for smallpox is based on results from a clinical trial that compared Jynneos with ACAM2000, a previously FDA-approved smallpox vaccine, in about 400 healthy adults aged 18-42 years. Adults who received Jynneos had a noninferior immune response to those who received ACAM2000. In addition, safety was assessed in 7,800 people who received at least one vaccine dose, with the most commonly reported side effects including pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache, and fatigue.

The effectiveness of Jynneos to prevent monkeypox – a disease similar to but somewhat milder than smallpox caused by the non–U.S.-native monkeypox virus – was inferred from antibody responses of participants in the smallpox clinical trial and from studies on nonhuman primates that showed protection from the monkeypox virus after being vaccinated with Jynneos.

“Routine [smallpox] vaccination of the American public was stopped in 1972 after the disease was eradicated in the U.S. and, as a result, a large proportion of the U.S., as well as the global population has no immunity,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect.”

This vaccine is also part of the Strategic National Stockpile, the nation’s largest supply of potentially lifesaving pharmaceuticals and medical supplies for use in a public health emergency, according to the announcement.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved Jynneos, a live, nonreplicating vaccine based on the vaccinia virus, for smallpox and monkeypox, becoming the first FDA-approved vaccine for the prevention of monkeypox disease.

FDA approval for Jynneos for smallpox is based on results from a clinical trial that compared Jynneos with ACAM2000, a previously FDA-approved smallpox vaccine, in about 400 healthy adults aged 18-42 years. Adults who received Jynneos had a noninferior immune response to those who received ACAM2000. In addition, safety was assessed in 7,800 people who received at least one vaccine dose, with the most commonly reported side effects including pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache, and fatigue.

The effectiveness of Jynneos to prevent monkeypox – a disease similar to but somewhat milder than smallpox caused by the non–U.S.-native monkeypox virus – was inferred from antibody responses of participants in the smallpox clinical trial and from studies on nonhuman primates that showed protection from the monkeypox virus after being vaccinated with Jynneos.

“Routine [smallpox] vaccination of the American public was stopped in 1972 after the disease was eradicated in the U.S. and, as a result, a large proportion of the U.S., as well as the global population has no immunity,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect.”

This vaccine is also part of the Strategic National Stockpile, the nation’s largest supply of potentially lifesaving pharmaceuticals and medical supplies for use in a public health emergency, according to the announcement.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved Jynneos, a live, nonreplicating vaccine based on the vaccinia virus, for smallpox and monkeypox, becoming the first FDA-approved vaccine for the prevention of monkeypox disease.

FDA approval for Jynneos for smallpox is based on results from a clinical trial that compared Jynneos with ACAM2000, a previously FDA-approved smallpox vaccine, in about 400 healthy adults aged 18-42 years. Adults who received Jynneos had a noninferior immune response to those who received ACAM2000. In addition, safety was assessed in 7,800 people who received at least one vaccine dose, with the most commonly reported side effects including pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache, and fatigue.

The effectiveness of Jynneos to prevent monkeypox – a disease similar to but somewhat milder than smallpox caused by the non–U.S.-native monkeypox virus – was inferred from antibody responses of participants in the smallpox clinical trial and from studies on nonhuman primates that showed protection from the monkeypox virus after being vaccinated with Jynneos.

“Routine [smallpox] vaccination of the American public was stopped in 1972 after the disease was eradicated in the U.S. and, as a result, a large proportion of the U.S., as well as the global population has no immunity,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect.”

This vaccine is also part of the Strategic National Stockpile, the nation’s largest supply of potentially lifesaving pharmaceuticals and medical supplies for use in a public health emergency, according to the announcement.

Find the full press release on the FDA website.

[email protected]

Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.

Mucosal vs. systemic immunity

Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.¹ The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.

Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
 

Live attenuated influenza vaccine (LAIV) induces mucosal immunity

Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).

Other vaccines likely need to induce mucosal immunity

Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.²

MDedge News

So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.

Let’s look at a novel “two-site” chlamydia vaccine

Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.³ This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:

1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).

2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).

3. Placebo (saline).

The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).

Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.

Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.

In summary

While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. One day we may be able to successfully immunize against more troublesome mucosal pathogens. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at [email protected].

References

1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.

2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).

3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.

Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.

Mucosal vs. systemic immunity

Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.¹ The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.

Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
 

Live attenuated influenza vaccine (LAIV) induces mucosal immunity

Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).

Other vaccines likely need to induce mucosal immunity

Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.²

MDedge News

So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.

Let’s look at a novel “two-site” chlamydia vaccine

Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.³ This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:

1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).

2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).

3. Placebo (saline).

The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).

Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.

Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.

In summary

While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. One day we may be able to successfully immunize against more troublesome mucosal pathogens. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at [email protected].

References

1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.

2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).

3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.

Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.

Mucosal vs. systemic immunity

Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.¹ The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.

Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
 

Live attenuated influenza vaccine (LAIV) induces mucosal immunity

Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).

Other vaccines likely need to induce mucosal immunity

Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.²

MDedge News

So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.

Let’s look at a novel “two-site” chlamydia vaccine

Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.³ This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:

1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).

2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).

3. Placebo (saline).

The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).

Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.

Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.

In summary

While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. One day we may be able to successfully immunize against more troublesome mucosal pathogens. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at [email protected].

References

1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.

2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).

3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The measles outbreak in New York City, the largest in the nation this year, has officially ended, Mayor Bill de Blasio and city health officials announced Sept. 3.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Ending the measles outbreak required extensive collaboration with community organizations and Jewish leaders. They helped encourage vaccinations and achieve record immunization levels in parts of Brooklyn,” Mayor de Blasio said in a written statement. “As we head back to school this week, we just remain vigilant. To keep our children and communities safe, I urge all New Yorkers to get vaccinated. It’s the best defense we have.”

A measles outbreak is considered to be over when 42 days, or two incubation periods, have elapsed since the last affected persons in the area were no longer infectious. “That time period has now passed for the people most recently infected with measles and reported,” the city health department said in the statement.

Since the outbreak began in October of last year, 654 individuals were diagnosed with measles in the five boroughs of New York, although 72% occurred in the Williamsburg neighborhood of Brooklyn. Of those 654 cases, there have been 52 hospitalizations and 16 admissions to intensive care, according to the health department. The majority of affected people were under 18 years of age (80%), and most were either unvaccinated (73%) or incompletely vaccinated (7%).

The end of the measles outbreak also brings an end to the public health emergency that was declared on April 9 for parts of Brooklyn, the statement noted.

“Vaccination coverage has increased significantly since the emergency order, which has been supported by community-led efforts. We are grateful to the New Yorkers who shared the truth about vaccines and protected the health of their friends and neighbors through this outbreak,” city health commissioner Dr. Oxiris Barbot said in the statement.

[email protected]

The measles outbreak in New York City, the largest in the nation this year, has officially ended, Mayor Bill de Blasio and city health officials announced Sept. 3.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Ending the measles outbreak required extensive collaboration with community organizations and Jewish leaders. They helped encourage vaccinations and achieve record immunization levels in parts of Brooklyn,” Mayor de Blasio said in a written statement. “As we head back to school this week, we just remain vigilant. To keep our children and communities safe, I urge all New Yorkers to get vaccinated. It’s the best defense we have.”

A measles outbreak is considered to be over when 42 days, or two incubation periods, have elapsed since the last affected persons in the area were no longer infectious. “That time period has now passed for the people most recently infected with measles and reported,” the city health department said in the statement.

Since the outbreak began in October of last year, 654 individuals were diagnosed with measles in the five boroughs of New York, although 72% occurred in the Williamsburg neighborhood of Brooklyn. Of those 654 cases, there have been 52 hospitalizations and 16 admissions to intensive care, according to the health department. The majority of affected people were under 18 years of age (80%), and most were either unvaccinated (73%) or incompletely vaccinated (7%).

The end of the measles outbreak also brings an end to the public health emergency that was declared on April 9 for parts of Brooklyn, the statement noted.

“Vaccination coverage has increased significantly since the emergency order, which has been supported by community-led efforts. We are grateful to the New Yorkers who shared the truth about vaccines and protected the health of their friends and neighbors through this outbreak,” city health commissioner Dr. Oxiris Barbot said in the statement.

[email protected]

The measles outbreak in New York City, the largest in the nation this year, has officially ended, Mayor Bill de Blasio and city health officials announced Sept. 3.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Ending the measles outbreak required extensive collaboration with community organizations and Jewish leaders. They helped encourage vaccinations and achieve record immunization levels in parts of Brooklyn,” Mayor de Blasio said in a written statement. “As we head back to school this week, we just remain vigilant. To keep our children and communities safe, I urge all New Yorkers to get vaccinated. It’s the best defense we have.”

A measles outbreak is considered to be over when 42 days, or two incubation periods, have elapsed since the last affected persons in the area were no longer infectious. “That time period has now passed for the people most recently infected with measles and reported,” the city health department said in the statement.

Since the outbreak began in October of last year, 654 individuals were diagnosed with measles in the five boroughs of New York, although 72% occurred in the Williamsburg neighborhood of Brooklyn. Of those 654 cases, there have been 52 hospitalizations and 16 admissions to intensive care, according to the health department. The majority of affected people were under 18 years of age (80%), and most were either unvaccinated (73%) or incompletely vaccinated (7%).

The end of the measles outbreak also brings an end to the public health emergency that was declared on April 9 for parts of Brooklyn, the statement noted.

“Vaccination coverage has increased significantly since the emergency order, which has been supported by community-led efforts. We are grateful to the New Yorkers who shared the truth about vaccines and protected the health of their friends and neighbors through this outbreak,” city health commissioner Dr. Oxiris Barbot said in the statement.

[email protected]