Protein/AS01<sub>B</sub> vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors.

Nielsen, Carolyn M; Ogbe, Ane; Pedroza-Pacheco, Isabela; Doeleman, Susanne E; Chen, Yue; Silk, Sarah E; Barrett, Jordan R; Elias, Sean C et al. · Cell Rep Med · 2021

prospective_cohort · Level II

Where this comes from

Abstract

Interactions between B cells and CD4<sup>+</sup> T follicular helper (Tfh) cells are key determinants of humoral responses. Using samples from clinical trials performed with the malaria vaccine candidate antigen <i>Plasmodium falciparum</i> 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<sub>B</sub> adjuvant. We demonstrate that the protein/AS01<sub>B</sub> 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<sub>B</sub> 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.

Medical subject headings