STUDIES ON THE IMMUNOBIOLOGY OF MALARIA

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Immunity that provides protection against the morbidity and mortality of malaria remains poorly understood. Likewise, the immune responses that mediate protective immunity to subunit vaccination in animal models is also presently unclear. In the absence of reliable in vitro correlates of protective immunity and with the lack of a full understanding of what contributes to immunity to malaria, development of effective malaria vaccines will continue to be haphazard at best. The major goals of this project are to elicit and then define protective immunity against malaria in animal models. We have now elicited protective immunity by subunit vaccination with the major surface protein, MSP1, in both rodent (P. yoelii in mice) and primate (P. falciparum in Aotus monkeys) models. Although immunity in these model systems may be antibody-dependent, it appears that antibodies alone, as measured by ELISA, do not mediate protective immunity. A variety of in vitro assays have been undertaken to search for the mechanisms of this subunit vaccine-induced protective immunity. Vaccination with whole malaria parasites and Salmonella elicits protective immunity to P. vinckei in mice. The immunity in this animal model system is primarily cellular-mediated, CD4+ T cell-dependent and requires the spleen. We are using this model to study the contribution of the spleen in providing protective immunity and, in conjunction with recombinant Salmonella and BCG, to identify malaria parasite polypeptides (T cell epitopes) that lead to protection. As of January 1996, this project will terminate and any ongoing and future studies will be incorporated into the Recombinant Protein Expression Unit.