Genotypic analysis of Plasmodium falciparum malaria parasites in a clinical trial of RTS,S vaccination in combination with seasonal malaria chemoprevention

Both vaccination and seasonal chemoprevention are effective interventions against malaria, but both morbidity and mortality due to malaria remain high, particularly in sub-Saharan Africa. A recent clinical trial showed that the combination of these interventions provided substantial protection against malaria over a five-year period. We performed amplicon-based genotyping of highly polymorphic parasite antigens within 1,530 samples from this clinical trial. We evaluated the complexity of infection within these samples, finding that participants who received both interventions had less complex infections (fewer genetically distinct parasite strains) than participants who received either intervention given alone. We also evaluated the prevalence of parasites matching the vaccine construct CSP, at the level of haplotypes, epitopes, and individual amino acid changes. We found no significant differences in the prevalence of vaccine-matching alleles between vaccinated and unvaccinated groups. For context, this study genotyped about half as many non-vaccinated participants as the original phase 3 trial for RTS,S. While a comparable number of vaccinated individuals were genotyped in both studies, the infections in this study had less complex infections, leading to an overall lower number of parasite strains to analyze. These results suggest that the combination of therapies provides protection from infection, in addition to clinical disease, and they highlight the importance of continued molecular surveillance as malaria interventions are deployed.