Interactions between B cells and CD4 + T follicular helper (Tfh) cells are key determinants of humoral responses . Using samples from clinical trials performed with the malaria vaccine candidate antigen Plasmodium falciparum merozoite protein (PfRH5), we compare the frequency, phenotype, and gene expression profiles of PfRH5-specific circulating Tfh (cTfh) cells elicited by two leading human vaccine delivery platforms: heterologous viral vector prime boost and protein with AS01 B adjuvant . We demonstrate that the protein/AS01 B platform induces a higher-magnitude antigen-specific cTfh cell response and that this correlates with peak anti-PfRH5 IgG concentrations, frequency of PfRH5-specific memory B cells, and antibody functionality . Furthermore, our data indicate a greater Th2/Tfh2 skew within the polyfunctional response elicited following vaccination with protein/AS01 B as compared to a Th1/Tfh1 skew with viral vectors . These data highlight the impact of vaccine platform on the cTfh cell response driving humoral immunity, associating a high-magnitude, Th2-biased cTfh response with potent antibody production.
Index: AS01, T follicular helper cells, Tfh cells, Th1, Th2, adaptive immunity, antibody, clinical trials, heterologous viral vectors, malaria, vaccines