Phase 2b clinical study evaluating efficacy of RTS,S/AS01EinPlasmodium falciparum-exposed Kenyan adults treated with antimalarial chemopreventive drugs

ABSTRACT Background RTS,S/AS01 vaccine efficacy (VE) was previously shown to be lower in African adults than in malaria-naïve US adults, potentially due to concurrent Plasmodium falciparum ( Pf ) 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/AS01 E in conjunction with antimalarial chemopreventive drugs. Participants, grouped by baseline presence or absence of Pf infections, were randomized to receive RTS,S/AS01 E or rabies vaccine. Four groups received antimalarial drugs prior to immunization and were followed for six months to assess Pf infection. We included an additional group of adults not treated with antimalarial drugs for immunological assessment. Results VE (RTS,S/AS01 E versus rabies vaccine) was 34.8% (8.9%, 53.4%) and −24.0% (−97%, 22.4%) in baseline Pf -positive and baseline Pf -negative participants, respectively. In RTS,S/AS01 E recipients, there were no statistical differences in anti-circumsporozoite (CS) antibody titers in baseline Pf- positive or Pf -negative participants, or in susceptibility to infection during the post-vaccination follow-up period. Drug treatment did not improve anti-CS antibody titers. Conclusions Treating Pf infections during vaccination does not result in increased VE. Anti-CS antibody responses to vaccination do not differ with baseline Pf infection status, drug treatment, or susceptibility to Pf infections. Clinical Trial Registration NCT04661579; PACTR202006896481432