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

Circulating T-follicular helper (cT FH ) cells have the potential to provide an additional correlate of protection against Plasmodium falciparum ( Pf ) 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 Pf- schizont egress antigen-1 ( Pf SEA-1A) and Pf -glutamic acid-rich protein ( Pf 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, Pf SEA-1A and Pf GARP, while adults had a narrow profile centering on cT FH 17- and cT FH 1/17-like subsets following stimulation with Pf GARP only. Because T FH 17 cells are involved in the maintenance of memory antibody responses within the context of parasitic infections, our results suggest that Pf GARP might generate longer-lived antibody responses compared to Pf 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.