The role of regulatory T cells in immunity to malaria (360G-Wellcome-109026_Z_15_A)

In malaria vaccine trials conducted in the target population of semi-immune people from endemic African countries, vaccine immunogenicity is sometimes substantially reduced compared to European malaria-naïve participants. This could result from the suppression of vaccine-induced immune responses by regulatory T cells (Tregs) acquired through prior malaria infections, however there are few studies in man which have previously explored this. Using samples from controlled human malaria infection studies in semi-immune Kenyan individuals, we will investigate how Tregs affect natural immunity to infection and see if increased Treg responses correlate with vaccine efficacy following malaria challenge in participants with varying prior exposures to malaria. We will also directly compare the effect and induction of Tregs in different pre-erythrocytic candidate vaccines and adjuvants to understand how vaccine-specific effects might affect Treg responses. Additionally, we will investigate if malaria-induced Tregs affect responses to other childhood vaccines. Single cell transcriptomic analysis using the Fluidigm platform will be employed to explore the phenotype and functional heterogeneity of Tregs. This will provide insight into the mechanisms by which Tregs are involved in immunity to malaria. This work will have important implications for the design and evaluation of malaria vaccines for use in endemic populations.