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

Background Circulating T-follicular helper (cTFH) 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 cTFH subsets to individual malaria antigens is vital to understanding the variation observed in antibody responses and identifying promising malaria vaccine candidates. Methods Using spectral flow cytometry and unbiased clustering analysis we assessed antigen-specific cTFH cell recall responses in vitro to malaria vaccine candidates Pf SEA-1A and Pf GARP within a cross-section of children and adults living in a malaria holoendemic region of western Kenya. Findings In children, a broad array of cTFH 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 cTFH17- and cTFH1/17-like subsets following stimulation with Pf GARP only. Interpretation Because TFH17 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 cTFH profiles when assessing interdependent correlates of protective immunity. ### Competing Interest Statement The authors have declared no competing interest.