Background: T-follicular helper CD4 T cells (TfH) are the key T cell subset responsible for mediating B cell activation and antibody induction during infection. The induction of different TfH subsets appears to be pathogen-specific. However, in human malaria infection, the specific TfH subsets required for the induction of protective antibodies has not been identified, and the impact of age on TfH subsets activation during P. falciparum infection is unknown.
Methods: Here, we assessed TfH responses children aged 6 months to 10 years residing in settings of high malaria transmission in Uganda via flow cytometry. Concurrently, the level and function of naturally acquired P. falciparum antibodies responses to blood stage parasites were measured by ELISA.
Results/Conclusions: We detected high levels of IgM and cytophillic subclasses, IgG1 and IgG3 in the majority of serum samples tested. We found that these serum antibodies promoted complement deposition on whole merozoites and merozoite antigens, MSP2 and AMA1. Furthermore, serum antibodies had the potential to cross-link Fc receptors to promote opsonic phagocytosis. The acquisition of functional antibodies increased with host age and was associated with protection against clinical malaria. Our results also showed a key role of IgG3 in mediating functional antibody responses. Associations of TfH with age, prior malaria exposure and antibody induction will be assessed and TfH responses associated with functional antibodies identified. These findings have major implications to further understand the appropriate TfH responses required to increase malaria vaccine efficacy.