Immune responses to Plasmodium falciparum-merozoite surface protein 1 (MSP1) antigen, II.: Induction of parasite-specific immunoglobulin G in unsensitized human B cells after in vitro T-cell priming with MSP119

A baculovirus recombinant antigen corresponding to the C-terminal 19000 MW fragment of Plasmodium falciparum merozoite surface protein 1 (MSPl(19)), has been used to prime T cells from individuals with no previous exposure to malaria, to provide help for the induction of a parasite specific antibody response in vitro. Although MSPI,, alone could induce a small but detectable T-cell response, which included interleukin-4 (IL-4) secretion, this response was significantly increased by the presence of IL-2. In addition, IL-4 was shown to synergize with IL-2 for the induction of antigen-specific T-cell responses. If interferon-gamma (IFN-gamma), IL-12, or neutralizing anti-IL-4 antibody was present at the time of priming, the T-cell responses were abolished. Parasite-specific immunoglobulin G (IgC) could be detected after secondary restimulation with MSPl(19), IL-10 and anti-CD40 monoclonal antibody in cultures containing MSPl(19), primed T cells, autologous B cells, IL-2 and IL-4. No antibody was secreted in the absence of primed T cells in this B-cell culture assay. These data show that recombinant MSPI,,, a leading malaria vaccine candidate, can prime non-immune human lymphocytes under defined in vitro experimental conditions, which include regulatory cytokines and/or other costimulatory molecules. This is a complementary approach for exploring immunogenic mechanisms of potential vaccine candidates such as P. falciparum antigens in humans.