The impact of vaccine platform on the cellular drivers of humoral immunity (360G-Wellcome-209200_Z_17_Z)

The focus of this Fellowship proposal is on how vaccine platform affects the cellular drivers of humoral immunity, specifically memory B cells (mBCs) and T follicular helper (Tfh) cells. I will compare the leading Plasmodium falciparum blood-stage malaria candidate – RH5 – in two vaccine platforms: heterologous viral vectors (chimp adenovirus 63 prime, Modified Vaccinia Ankara boost) and protein with AS01 adjuvant. I have three main goals for this research. First, to compare the frequency and persistence of antigen-specific mBC and Tfh cells post-vaccination between vaccine platforms. Second, to identify the role vaccine platform plays in dictating Fc glycosylation profiles of anti-RH5 antibodies. Finally, to detect changes in protein expression in mBC and Tfh cells using RNAseq, indicating whether cellular pathways are differentially activated by vaccine platform. Taken together, these three sets of data will allow me to link mBC and Tfh responses to antibody quantity/quality, in the context of vaccine platform. Understanding how platform modulates mBC and Tfh responses will help us optimise vaccines to improve immunogenicity and protective efficacy. While my research will focus on blood-stage malaria, the conclusions should be translatable to other vaccine development programmes where antibodies are central to the mechanism of protection.