Human TFH responses to malaria specific antigen using a Kenyan cross sectional study

The goal of this study was to highlight the profile of the circulating T follicular helper (TFH) cells in children and adults living in high Plasmodium falciparum (Pf) transmission area and the responses of these specific T cells to in vitro stimulation by two Pf malaria specific antigens PfSEA-1A and PfGARP which are also investigated as vaccine candidates. Having a better understanding on how TFH cells reacts to vaccine candidates can help in down-selecting them. For this study, we used spectral flow cytometry and unbiased clustering analysis to identify the different type of TFH cells as well as assessing their specific cytokines and transcription factors profile responses to the two vaccine candidates PfSEA-1A and PfGARP. WE also used multiplex-bead based immunoassay to assess the Pf malaria serology of each participants. We found that in children, all the types of cTFH produced cytokines and transcription factors after stimulation whereas the specific response was mainly focus on the cTFH17 and cTFH1/17 in adults. Knowing that cTFH17 are associated with the maintenance of antibody memory responses, these results suggest that PfSEA-1A and PfGARP might trigger a better antibody response in adults compared to children. Moreover, we found that PfGARP induced significantly more of Bcl6 within cTFH cells, Bcl6 being an essential transcription factor for the cTFH function of helping B cell development and antibody production suggesting that it might be a better candidates than PfSEA-1A.