Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children:: single-blind extended follow-up of a randomised controlled trial

Background RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children. Methods We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE2 5-8 5). We now report VE in a single-blind phase up to month 21 (VE8 5-21). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature >= 37.5 degrees C and P falciparum asexual parasitaemia >2500 per mu L) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041. Findings During the single-blind phase, VE(8 5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2 5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2 5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02). Interpretation These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.