Efficacy of RTS,S/AS01E Only Seen in Baseline Parasitemic and Not Baseline Aparasitemic Plasmodium falciparum-Exposed, Drug-Treated Kenyan Adults

BACKGROUND: RTS,S/AS01 vaccine efficacy (VE) was previously shown as lower in African adults than in malaria-naive US adults, potentially due to concurrent Plasmodium falciparum infections. We investigated whether treatment of infection prior to vaccination would lead to improved VE and immunogenicity. METHODS: A phase 2b study in Kenyan adults evaluated the efficacy of RTS,S/AS01E in conjunction with antimalarial chemopreventive drugs. Participants, grouped by baseline presence or absence of P. falciparum infections, were randomized to receive RTS,S/AS01E or rabies vaccine. Four groups received antimalarial drugs prior to immunization and were followed for 6 months to assess P. falciparum infection. We included an additional group not treated with antimalarial drugs for immunological assessment. RESULTS: VE (RTS,S/AS01E vs rabies vaccine) was 34.8% (95% confidence interval [CI], 8.9% to 53.4%) and -24.0% (95% CI, -97% to 22.4%) in baseline P. falciparum-positive and P. falciparum-negative participants, respectively. In RTS,S/AS01E recipients, there were no statistical differences in anticircumsporozoite (anti-CS) antibody titers in baseline P. falciparum-positive or P. falciparum-negative participants, or in susceptibility to infection during the postvaccination follow-up period. Drug treatment did not improve anti-CS antibody titers. CONCLUSIONS: Treating P. falciparum infections during vaccination does not result in increased VE. Anti-CS antibody responses to vaccination do not differ with baseline P. falciparum infection status, drug treatment, or susceptibility to P. falciparum infections. CLINICAL TRIALS REGISTRATION: NCT04661579; PACTR202006896481432.