Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children

Abstract

Background. We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profi e, was immunogenic, and demonstrated eff cacy against Plasmodium falciparum malaria disease for 21 months. Methods. We conducted a randomized, controlled, phase 2b trial of RTS,S/AS02A in 2022 Mozambican children aged 1–4 years. We now report safety results for all randomized subjects and vaccine efficac (VE) fi dings for children in the Manhiça area over the 45-month surveillance period. Results. During the surveillance period, the VE (2.5–45) (VE over months 2.5–45 of surveillance) against a fir t or only episode of clinical malaria disease was 30.5% (95% confidenc interval [CI], 18.9%–40.4%; P ! .001 ), and the VE (2.5–45) against all episodes was 25.6% (95% CI, 11.9%–37.1%; P ! .001 ). When the same period was considered, the VE (2.5–45) for subjects protected against severe malaria was 38.3% (95% CI, 3.4%–61.3%; P p .045 ). At study month 45, the prevalence of P. falciparum was 34% lower in the RTS,S/AS02A group than in the control group (66 [12.2%] of 541 patients vs 101 [18.5%] of 547 patients) ( P p .004 ). Conclusion. These results show evidence that RTS,S/AS02A maintained protection during the 45-month sur- veillance period, and they highlight the feasibility of developing an effective vaccine against malaria. In combination with other malaria-control measures, such a vaccine could greatly contribute to reducing the intolerable global burden of this disease.