A PHASE 2 trial in Gabon found that the radiation-attenuated P. falciparum sporozoite (PfSPZ) malaria vaccine was safe in children aged 1–12 years but did not prevent infection with Plasmodium falciparum.
PfSPZ malaria vaccine trial in Gabon
The study, conducted at the Centre de Recherches Médicales de Lambaréné, evaluated the safety and efficacy of PfSPZ vaccine in 200 children. Participants were stratified by age and randomised 2:1 to receive either the vaccine or placebo across three doses. Prior to the final vaccination, all children received artemether-lumefantrine to clear latent parasitaemia. The trial’s co-primary endpoints included vaccine safety and efficacy, measured by time to first malaria infection over a 24-week follow-up period.
Malaria vaccine safety profile remains favourable
Safety outcomes were encouraging. Among vaccinated children, 25% reported systemic adverse events compared with 23% in the placebo group, with subjective fever being the most frequent. Importantly, the three grade 3 adverse events (two cases of elevated temperature and one fever) occurred only in the placebo group. Serious adverse events were documented in both arms but none were linked to vaccination. No treatment-related deaths occurred, underscoring the favourable safety profile of the PfSPZ malaria vaccine in a paediatric population.
Low efficacy highlights prevention challenges
Despite good tolerability, efficacy results were disappointing. Within 26 weeks, 19% of vaccine recipients and 23% of placebo recipients developed malaria infections, yielding an age-adjusted vaccine efficacy of just 9% (95% CI: -75–53). These findings contrast with protective effects previously reported in adults and raise questions about the vaccine’s performance in children. Researchers note that different dosing strategies, alternative formulations, or presumptive treatment regimens during immunisation may be necessary to improve protection in paediatric populations.
The PfSPZ malaria vaccine demonstrated strong safety but no protective efficacy in children in Gabon. Future studies are exploring enhanced formulations and strategies to achieve effective malaria prevention in this vulnerable age group.
Reference
Agnandji ST et al. Safety, tolerability, and protective efficacy of a radiation-attenuated, whole sporozoite malaria vaccine in children in Gabon: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2025; DOI: 10.1016/S1473-3099(25)00434-7.
