T follicular helper cell profiles differ by malaria antigen and for children compared to adults
Abstract
Background
Circulating T-follicular helper (cTFH) cells have the potential to provide an additional correlate of protection againstPlasmodium falciparum(Pf)as they are essential to promote B cell production of long-lasting antibodies. Assessing the specificity of cTFHsubsets 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 cTFHcell recall responsesin vitroto malaria vaccine candidatesPfSEA-1A andPfGARP within a cross-section of children and adults living in a malaria holoendemic region of western Kenya.
Findings
In children, a broad array of cTFHsubsets (defined by cytokine and transcription factor expression) were reactive to both malaria antigens,PfSEA-1A andPfGARP, while adults had a narrow profile centering on cTFH17- and cTFH1/17-like subsets following stimulation withPfGARP only.
Interpretation
Because TFH17 cells are involved in the maintenance of memory antibody responses within the context of parasitic infections, our results suggest thatPfGARP might generate longer lived antibody responses compared toPfSEA-1A. These findings have intriguing implications for evaluating malaria vaccine candidates as they highlight the importance of including cTFHprofiles when assessing interdependent correlates of protective immunity.
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