A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria

A highly effective malaria vaccine remains elusive despite decades of research. Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), a metabolically active, nonreplicating, whole parasite vaccine demonstrated safety and vaccine efficacy (VE) against endemic P. falciparum for 6 months in Malian adults receiving a five-dose regimen. Safety, immunogenicity, and VE of a three-dose regimen were assessed in adults in Balonghin, Burkina Faso in a two-component study: an open-label dose escalation trial with 32 participants followed by a double-blind, randomized, placebo-controlled trial (RCT) with 80 participants randomized to receive three doses of 2.7 × 106 PfSPZ (N = 39) or normal saline (N = 41) just before malaria season. To clear parasitemia, artesunate monotherapy was administered before first and last vaccinations. Thick blood smear microscopy was performed on samples collected during illness and every 4 weeks for 72 weeks after last vaccinations, including two 6-month malaria transmission seasons. Safety outcomes were assessed in all 80 participants who received at least one dose and VE for 79 participants who received three vaccinations. Myalgia was the only symptom that differed between groups. VE (1 − risk ratio; primary VE endpoint) was 38% at 6 months (P = 0.017) and 15% at 18 months (0.078). VE (1 − hazard ratio) was 48% and 46% at 6 and 18 months (P = 0.061 and 0.018). Two weeks after the last dose, antibodies to P. falciparum circumsporozoite protein and PfSPZ were higher in protected versus unprotected vaccinees. A three-dose regimen of PfSPZ Vaccine demonstrated safety and efficacy against malaria infection in malaria-experienced adults. Description A three-dose regimen of a whole sporozoite vaccine in adults in Burkina Faso, West Africa, demonstrated safety and efficacy against malaria infection. Malaria vaccine advance Malaria Vaccine AdvanceThe Plasmodium falciparum sporozoite (PfSPZ) vaccine is a non-replicating whole parasite vaccine that has shown promising results in preliminary clinical trials. Simira et al. present findings from two clinical trials in adults living in malaria-endemic areas of Burkina Faso receiving a three-dose regimen. This study included an open-label dose escalation trial with 32 adults and a double-blind, randomized, placebo-controlled trial with 80 adults in which 39 were given three doses of 2.7x106 PfSPZ vaccine and 41 individuals were given normal saline. Thick blood smears collected throughout vaccination period and for 72 weeks following last vaccination were used to measure incidence of parasitemia. Statistical analyses indicated efficacy at six months post-vaccination with an indication of longer protection. These clinical findings show that the PfSPZ vaccine is safe and effective for adults living with endemic malaria.-CF