A recent study published in The New England Journal of Medicine highlights a new malaria vaccine achieving an unprecedented 89% efficacy by targeting late-liver-stage antigens of the Plasmodium falciparum parasite. Conducted in the Netherlands, this research evaluated the safety, immune response, and protective efficacy of a genetically attenuated (GA) parasite in healthy adults.
The study addresses the stagnation in malaria eradication efforts, emphasizing the need for more effective vaccination strategies. Current vaccines like RTS,S/AS01 and modified recombinant R21 provide limited protection, particularly in infants. The trial utilized a dose-escalation safety phase and a double-blind efficacy phase, involving participants receiving up to 50 bites from GA2-infected mosquitoes.
During the trial, conducted from September 2021 to January 2022, 75 malaria-naïve adults were screened, with 43 enrolled. The results showed no breakthrough blood-stage infections, reinforcing the safety profile of the GA2 parasite. In the efficacy phase, GA2 demonstrated 89% protection against controlled human malaria infection (CHMI), compared to 12% for GA1 and none for the placebo group.
Immunogenicity analysis revealed increased antibodies against Plasmodium falciparum CSP in GA2 and GA1 groups, with GA2 eliciting a more robust cellular immune response. Participants immunized with GA2 exhibited higher levels of polyfunctional CD4+ and Vδ2+ γδ T cells, critical for protective immunity.
The findings suggest that late-arresting parasites (GA2) induce stronger protective immunity compared to early-arresting models. Further studies are needed to confirm these results in larger populations and assess long-term efficacy in malaria-endemic regions.