Immunity to the sporozoite stage of the malaria parasite is T cell dependent and effector mechanism include both humoral and cell mediated immune responses. An immunodominant B cell epitope of the circumsporozoite (CS) protein of the malaria parasite has been defined using antisporozoite antibodies produced in both naturally infected and experimentally immunized hosts. The antigenic determinants which activate T cells during an antisporozoite immune response have not yet been identified. The goal of the proposed research is to identify the T cell epitopes of the CS protein which function in the induction of protective immunity. Cells of various strains of mice immunized with sporozoite of the rodent malaria, P. berghei, will be challenged in vitro with synthetic and recombinant analogues of the CS protein and attempts will be made to define an in vitro assay which correlates with protection in vivo. T cell lines and clones will be isolated from the immunized mice to study T cell fine specificity and the immune function of monoclonal T cell populations. Synthetic peptides or recombinant proteins containing the T cell epitopes and the immunodominant B cell epitope(s) of the P. berghei CS protein will be used to immunize mice of various strains to test for the ability of these CS antigen constructs to induce protection in vivo. Murine congenic strains will also be used to define the T cell epitope(s) of the CS proteins of the human malaria, P. vivax. the fine specificity of murine T cell anti vivax clones will be compared to human T cell clones derived from individuals living in areas of endemic P. vivax malaria. The identification of the T cell epitope(s) of the CS protein will facilitate the design of a sporozoite vaccine which effectively induces cell mediated as well as humoral immunity. The studies will also establish the optimal in vitro assay(s) for measuring protective immunity and provide a means of monitoring the development of functional antisporozoite immune responses in naturally infected or vaccinated hosts.
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