T-follicular helper cell profiles differ by malaria antigen and for children compared to adults.

Abstract

Circulating T-follicular helper (cT_FH) cells have the potential to provide an additional correlate of protection against <i>Plasmodium falciparum</i> (<i>Pf</i>) as they are essential to promote B-cell production of long-lasting antibodies. Assessing the specificity of cT_FH subsets to individual malaria antigens is vital to understanding the variation observed in antibody responses and identifying promising malaria vaccine candidates. Using spectral flow cytometry and unbiased clustering analysis, we assessed antigen-specific cT_FH cell recall responses in vitro to malaria vaccine candidates <i>Pf-</i>schizont egress antigen-1 (<i>Pf</i>SEA-1A) and <i>Pf</i>-glutamic acid-rich protein (<i>Pf</i>GARP) within a cross-section of children and adults living in a malaria-holoendemic region of western Kenya. In children, a broad array of cT_FH subsets (defined by cytokine and transcription factor expression) were reactive to both malaria antigens, <i>Pf</i>SEA-1A and <i>Pf</i>GARP, while adults had a narrow profile centering on cT_FH17- and cT_FH1/17-like subsets following stimulation with <i>Pf</i>GARP only. Because T_FH17 cells are involved in the maintenance of memory antibody responses within the context of parasitic infections, our results suggest that <i>Pf</i>GARP might generate longer-lived antibody responses compared to <i>Pf</i>SEA-1A. These findings have intriguing implications for evaluating malaria vaccine candidates as they highlight the importance of including cT_FH profiles when assessing interdependent correlates of protective immunity.