Conference Agenda

Effective malaria interventions are essential to reduce disease burden in children. Combining RTS,S vaccination with seasonal antimalarial chemoprevention was shown to enhance efficacy against clinical malaria among children by ~72% over the first year compared to either intervention alone. However, over four years, efficacy of this combination steadily decreased despite annual boosters. Protective antibodies were shown to peak following primary vaccination but became progressively lower with each annual booster. It is unknown what drives poor antibody responses to boosters, which likely vary between different antibody isotypes and antigenic targets, and if host factors such as viral co-infections and micronutrient deficiencies are implicated in this suboptimal response.

To address these knowledge gaps, we evaluated plasma samples from young children (n=1,929) in West Africa who received RTS,S and subsequent boosters with or without seasonal chemoprevention over four years as part of a phase-III clinical trial. We found that repeated vaccine doses had differential effects on antibody responses, which varied by the antigenic region of the vaccine. We also investigated the impact of host factors on these responses. By improving our understanding of the immune response to repeated booster doses, this work informs optimal RTS,S implementation strategies to improve vaccine efficacy and longevity.