A recent study published in The Lancet assessed the safety and efficacy of the PfSPZ Vaccine for malaria in adults and women planning to conceive. The vaccine was safe and well-tolerated in Mali, West Africa. The lower dose and the higher dose, given with presumptive antimalarial treatment on a 4-week schedule, showed significant efficacy against Plasmodium falciparum parasitaemia and clinical malaria over two transmission seasons in women of childbearing age and during pregnancy. The vaccine did not show efficacy when administered without the presumptive antimalarial treatment.1
The vaccine's performance was evaluated across two trials, Phase 1 MLSPZV3 (2018-2019) and Phase 2 MLSPZV4 (2019-2021), during two malaria transmission seasons. In MLSPZV4, the vaccine showed significant efficacy with 41% (900,000 doses) and 54% (1.8 million doses) reduction in parasitaemia in the first year, improving to 61% (900,000 doses) and 45% (1.8 million doses) in the second year. Vaccine efficacy during the first pregnancies was 57% for the 900,000 doses and 49% for the 1.8 million doses. Among women who became pregnant within 24 weeks after the third dose, efficacy was 65% (900,000 doses) and 86% (1.8 million doses).1
Main Takeaways
- The PfSPZ Vaccine demonstrated significant efficacy against Plasmodium falciparum when administered with presumptive antimalarial treatment, but not when given alone.
- The vaccine was generally safe and well-tolerated, with mild adverse events and one unrelated maternal death in the higher dose group, while miscarriage rates were similar between vaccine and placebo groups.
- The vaccine showed varying efficacy between trials, with significant results in Phase 2 (MLSPZV4) compared to limited efficacy in Phase 1 (MLSPZV3), emphasizing the importance of the treatment regimen.
In MLSPZV3, involving 478 adults, the PfSPZ Vaccine showed no/less significant efficacy: 27% for the 4-week schedule and 16% for the 16-week schedule. In MLSPZV4, involving 407 women, significant efficacy was observed with both vaccine doses against parasitaemia and clinical malaria. Adverse events were mild, with one unrelated maternal death due to peritonitis in the 1.8 million dose group. Miscarriage rates were similar across vaccine and placebo groups. The study supports the use of the PfSPZ Vaccine as part of malaria prevention strategies in endemic regions.1
Participants in MLSPZV3 were randomized (2:1) to receive three doses of either the 900,000 PfSPZ Vaccine or saline placebo on a 4-week or 16-week schedule. In MLSPZV4, women were randomly assigned (1:1:1) to receive three doses of 900,000 or 1.8 million PfSPZ Vaccine, or saline placebo, all on a 4-week schedule. All participants received presumptive artemether-lumefantrine two weeks before the third dose and booster in MLSPZV3 and before the first dose in MLSPZV4. Primary outcomes included safety and tolerability within 7 days of each dose. Secondary outcomes assessed vaccine efficacy against P falciparum parasitaemia.1
According to WHO, P falciparum is the most dangerous malaria parasite, primarily spread by infected female Anopheles mosquitoes. It can also be transmitted through blood transfusions and contaminated needles. Common symptoms include fever and chills, while severe cases can lead to fatigue and convulsions. In 2022, there were 249 million malaria cases and 608,000 deaths globally, with the majority in Africa. Prevention includes avoiding mosquito bites, using insecticide-treated nets, and taking preventive medicines. The RTS,S/AS01 and R21/Matrix-M vaccines reduce malaria incidence. Early diagnosis and treatment with artemisinin-based therapies are essential, though drug resistance is a growing concern.2
The study had some limitations, including the single unrelated maternal death in the 1.8 million dose group and the mild adverse events which may not fully capture all potential risks. The efficacy results are specific to the studied population and may not generalize to other regions or populations.1
The PfSPZ Vaccine, when administered with presumptive antimalarial treatment, showed significant efficacy against P falciparum parasitaemia and clinical malaria in Mali. The vaccine was well-tolerated, and its use in women planning to conceive demonstrates potential for broader application in malaria-endemic regions. Further studies are needed to confirm long-term efficacy and safety in diverse populations.
References
Diawara H, Healy S, Mwakingwe-Omari A, et. al. Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. The Lancet. August 14, 2024. Accessed August 20, 2024. DOI: https://doi.org/10.1016/S1473-3099(24)00360-8
