Vaccine can protect some adults from malaria long-term

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.

Malaria-carrying mosquito

Photo by James Gathany

An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.

Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.

Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.

Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.

In addition, the researchers said the vaccine was well-tolerated.

“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”

Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.

The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.

The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.

In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.

Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.

To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).

Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.

Safety

Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).

Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.

Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).

There were no serious adverse events attributed to vaccination.

Efficacy

The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.

The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×10⁵ PfSPZ IV, compared to 73% with 4 doses of 2.7×10⁵ PfSPZ IV.

The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×10⁵ PfSPZ IV, compared to 55% with 4 doses of 2.7×10⁵ PfSPZ IV.

In other words, after 4 immunizations with PfSPZ at 2.7×10⁵ IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.

Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.

Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×10⁵ to 2.7×10⁶ PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.