Antibody and T cell responses associated with experimental human malaria infection or vaccination show limited relationships

This study examined specific antibody and T cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via 5 bites of Plasmodium falciparum-infected mosquitos, with individuals reaching patent infection by 11-12 days, having harboured 4-5 blood stage cycles prior to drug clearance. Infection elicited a robust antibody response against Merozoite Surface Protein-119, correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T cell responses were detected in the form of IFNγ and IL-4 ELIspot, but their magnitude did not correlate with magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing IFNγ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-Apical Membrane Antigen-1 antibody titres. Overall, these findings suggest that cognate T cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related.