Long‐Term Safety and Efficacy of the RTS,S/AS02A Malaria Vaccine in Mozambican Children

Abstract

We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profile, was immunogenic, and demonstrated efficacy against Plasmodium falciparum malaria disease for 21 months. 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 efficacy (VE) findings for children in the Manhiça area over the 45-month surveillance period. During the surveillance period, the VE_(2.5–45) (VE over months 2.5–45 of surveillance) against a first or only episode of clinical malaria disease was 30.5% (95% confidence 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 = .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 = .004). These results show evidence that RTS,S/AS02A maintained protection during the 45-month surveillance 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. ClinicalTrials.gov identifiers NCT00197041 and NCT00323622.