Memory B-cell and antibody responses induced by Plasmodium falciparum sporozoite immunization

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Abstract

Background.Immunization of healthy volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS-immunization) induces sterile protection from malaria. Antibody responses are long known to contribute to naturally acquired immunity against malaria, but their association with sterile protection after whole sporozoite immunization is not well established. We therefore studied the induction and kinetics of malaria antigen-specific antibodies and memory B-cells (MBC) during CPS-immunization and their correlation with protection from challenge infection.Methods.We assessed humoral reactivity to nine antigens representing different life-cycle stages of the malaria parasite by performing standardized MBC ELISpot and ELISA on peripheral blood mononuclear cells and plasma samples from 38 Dutch volunteers enrolled in two randomized controlled clinical trials (NCT01236612, NCT01218893).Results.MBC and antibodies recognizing pre-erythrocytic and cross-stage antigens were gradually acquired during CPS-immunization. The magnitude of these humoral responses did not correlate with protection, but directly reflected parasite exposure in CPS-immunization and challenge.Conclusions.Humoral responses to the malarial antigens CircumSporozoite Protein, Liver-Stage Antigen-1, Apical Membrane Antigen-1 and Merozoite Surface Protein-1 do not to predict protection from challenge infection, but can be used as sensitive marker of recent parasite exposure.