Investigational vaccine can prevent malaria

Changing the route of administration has significantly improved the efficacy of an investigational malaria vaccine, according to a study published in Science.

The vaccine, called PfSPZ, is composed of live but weakened sporozoites of Plasmodium falciparum.

In a previous clinical trial, the vaccine proved largely ineffective at preventing malaria. But in that study, PfSPZ was administered either intradermally or subcutaneously.

In a new phase 1 study, researchers administered the vaccine intravenously at varying doses. And they found that, at high doses, PfSPZ offered protection against malaria in most subjects.

“In this trial, we showed, in principle, that sporozoites can be developed into a malaria vaccine that confers high levels of protection . . . ,” said study author Robert A. Seder, MD, chief of the Cellular Immunology Section of the NIAID Vaccine Research Center in Bethesda, Maryland.

Dr Seder and his colleagues tested the vaccine in 57 healthy adult volunteers, aged 18 to 45 years, who never had malaria. Forty of the subjects received the vaccine, and 17 did not.

Adverse reactions

To evaluate safety, the researchers divided recipients into groups receiving 2 to 6 intravenous doses of PfSPZ vaccine at increasing dosages. After vaccination, the team monitored subjects closely for 7 days.

There were no malaria infections related to vaccination. However, there were a number of adverse events.

Nine subjects had mild pain/tenderness or bruising, and 1 had moderate bruising at the injection site. Sixteen participants had mild solicited systemic reactogenicity, 4 had moderate, and 1 had severe reactogenicity.

Sixteen subjects also had transient, asymptomatic increases in aspartate aminotransferase and/or alanine aminotransferase that was possibly related to vaccination.

Response and protection

Based on blood measurements, the researchers found that subjects who received a higher total dosage of PfSPZ vaccine generated more antibodies against malaria and more T cells specific to the vaccine.

To evaluate whether and how well the PfSPZ vaccine prevented malaria infection, each participant—both vaccinated individuals and the control group—was exposed to bites by 5 mosquitoes carrying the P falciparum strain.

This took place 3 weeks after participants received their final vaccination. The researchers monitored the subjects as outpatients for 7 days and then admitted them to the clinic, where they stayed until they were diagnosed with malaria, treated with antimalarial drugs and cured of infection, or shown to be free of infection.

The researchers found that higher dosages of PfSPZ vaccine were associated with protection against malaria infection. Three of the 15 participants who received higher dosages of the vaccine became infected, compared to 16 of 17 subjects in the lower-dosage group.

Among the 12 participants who received no vaccine, 11 became infected with malaria after the mosquito challenge.

“[T]hese trial results are a promising first step in generating high-level protection against malaria, and they allow for future studies to optimize the dose, schedule, and delivery route of the candidate vaccine,” Dr Seder said.

A number of follow-up studies are planned, including research to evaluate the vaccine’s different dose schedules, possible protection against other Plasmodium strains, and the durability of protection.

The researchers may also evaluate whether higher doses administered subcutaneously or intradermally provide the same level of protection as that found in this study.

The PfSPZ vaccine was developed by scientists at Sanaria Inc., of Rockville, Maryland.

Changing the route of administration has significantly improved the efficacy of an investigational malaria vaccine, according to a study published in Science.

The vaccine, called PfSPZ, is composed of live but weakened sporozoites of Plasmodium falciparum.

In a previous clinical trial, the vaccine proved largely ineffective at preventing malaria. But in that study, PfSPZ was administered either intradermally or subcutaneously.

In a new phase 1 study, researchers administered the vaccine intravenously at varying doses. And they found that, at high doses, PfSPZ offered protection against malaria in most subjects.

“In this trial, we showed, in principle, that sporozoites can be developed into a malaria vaccine that confers high levels of protection . . . ,” said study author Robert A. Seder, MD, chief of the Cellular Immunology Section of the NIAID Vaccine Research Center in Bethesda, Maryland.

Dr Seder and his colleagues tested the vaccine in 57 healthy adult volunteers, aged 18 to 45 years, who never had malaria. Forty of the subjects received the vaccine, and 17 did not.

Adverse reactions

To evaluate safety, the researchers divided recipients into groups receiving 2 to 6 intravenous doses of PfSPZ vaccine at increasing dosages. After vaccination, the team monitored subjects closely for 7 days.

There were no malaria infections related to vaccination. However, there were a number of adverse events.

Nine subjects had mild pain/tenderness or bruising, and 1 had moderate bruising at the injection site. Sixteen participants had mild solicited systemic reactogenicity, 4 had moderate, and 1 had severe reactogenicity.

Sixteen subjects also had transient, asymptomatic increases in aspartate aminotransferase and/or alanine aminotransferase that was possibly related to vaccination.

Response and protection

Based on blood measurements, the researchers found that subjects who received a higher total dosage of PfSPZ vaccine generated more antibodies against malaria and more T cells specific to the vaccine.

To evaluate whether and how well the PfSPZ vaccine prevented malaria infection, each participant—both vaccinated individuals and the control group—was exposed to bites by 5 mosquitoes carrying the P falciparum strain.

This took place 3 weeks after participants received their final vaccination. The researchers monitored the subjects as outpatients for 7 days and then admitted them to the clinic, where they stayed until they were diagnosed with malaria, treated with antimalarial drugs and cured of infection, or shown to be free of infection.

The researchers found that higher dosages of PfSPZ vaccine were associated with protection against malaria infection. Three of the 15 participants who received higher dosages of the vaccine became infected, compared to 16 of 17 subjects in the lower-dosage group.

Among the 12 participants who received no vaccine, 11 became infected with malaria after the mosquito challenge.

“[T]hese trial results are a promising first step in generating high-level protection against malaria, and they allow for future studies to optimize the dose, schedule, and delivery route of the candidate vaccine,” Dr Seder said.

A number of follow-up studies are planned, including research to evaluate the vaccine’s different dose schedules, possible protection against other Plasmodium strains, and the durability of protection.

The researchers may also evaluate whether higher doses administered subcutaneously or intradermally provide the same level of protection as that found in this study.

The PfSPZ vaccine was developed by scientists at Sanaria Inc., of Rockville, Maryland.

Changing the route of administration has significantly improved the efficacy of an investigational malaria vaccine, according to a study published in Science.

The vaccine, called PfSPZ, is composed of live but weakened sporozoites of Plasmodium falciparum.

In a previous clinical trial, the vaccine proved largely ineffective at preventing malaria. But in that study, PfSPZ was administered either intradermally or subcutaneously.

In a new phase 1 study, researchers administered the vaccine intravenously at varying doses. And they found that, at high doses, PfSPZ offered protection against malaria in most subjects.

“In this trial, we showed, in principle, that sporozoites can be developed into a malaria vaccine that confers high levels of protection . . . ,” said study author Robert A. Seder, MD, chief of the Cellular Immunology Section of the NIAID Vaccine Research Center in Bethesda, Maryland.

Dr Seder and his colleagues tested the vaccine in 57 healthy adult volunteers, aged 18 to 45 years, who never had malaria. Forty of the subjects received the vaccine, and 17 did not.

Adverse reactions

To evaluate safety, the researchers divided recipients into groups receiving 2 to 6 intravenous doses of PfSPZ vaccine at increasing dosages. After vaccination, the team monitored subjects closely for 7 days.

There were no malaria infections related to vaccination. However, there were a number of adverse events.

Nine subjects had mild pain/tenderness or bruising, and 1 had moderate bruising at the injection site. Sixteen participants had mild solicited systemic reactogenicity, 4 had moderate, and 1 had severe reactogenicity.

Sixteen subjects also had transient, asymptomatic increases in aspartate aminotransferase and/or alanine aminotransferase that was possibly related to vaccination.

Response and protection

Based on blood measurements, the researchers found that subjects who received a higher total dosage of PfSPZ vaccine generated more antibodies against malaria and more T cells specific to the vaccine.

To evaluate whether and how well the PfSPZ vaccine prevented malaria infection, each participant—both vaccinated individuals and the control group—was exposed to bites by 5 mosquitoes carrying the P falciparum strain.

This took place 3 weeks after participants received their final vaccination. The researchers monitored the subjects as outpatients for 7 days and then admitted them to the clinic, where they stayed until they were diagnosed with malaria, treated with antimalarial drugs and cured of infection, or shown to be free of infection.

The researchers found that higher dosages of PfSPZ vaccine were associated with protection against malaria infection. Three of the 15 participants who received higher dosages of the vaccine became infected, compared to 16 of 17 subjects in the lower-dosage group.

Among the 12 participants who received no vaccine, 11 became infected with malaria after the mosquito challenge.

“[T]hese trial results are a promising first step in generating high-level protection against malaria, and they allow for future studies to optimize the dose, schedule, and delivery route of the candidate vaccine,” Dr Seder said.

A number of follow-up studies are planned, including research to evaluate the vaccine’s different dose schedules, possible protection against other Plasmodium strains, and the durability of protection.

The researchers may also evaluate whether higher doses administered subcutaneously or intradermally provide the same level of protection as that found in this study.

The PfSPZ vaccine was developed by scientists at Sanaria Inc., of Rockville, Maryland.