T-CELL RESPONSES TO REPEAT AND NON-REPEAT REGIONS OF THE CIRCUMSPOROZOITE PROTEIN DETECTED IN VOLUNTEERS IMMUNIZED WITH PLASMODIUM-FALCIPARUM SPOROZOITES

The design of a malarial vaccine based on the circumsporozoite (CS) pr otein, a major surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inc lusion in recombinant or synthetic vaccine candidates. We have investi gated the specificity and function of a series of T cell clones, deriv ed from volunteers immunized with Plasmodium falciparum sporozoites, i n an effort to identify relevant epitopes in the immune response to th e pre-erythrocytic stages of the parasite. CD4+ T cell clones were obt ained which specifically recognized a repetitive epitope located in th e 5' repeat region of the CS-protein. This epitope, when conjugated to the 3' repeat region in a synthetic MAPs construct, induced high lite rs of antisporozoite antibodies in C57B1 mice. A second T cell epitope , which mapped to aa 326-345 of the carboxy terminal was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite -immunized volunteers. The demonstration of CD4+ CTL in the human volu nteers, and the recent studies in the rodent model (Renia et al., 1991 ; Tsuji et al., 1990), suggest that CS-specific CD4+ T cells, in addit ion to their indirect role as helper cells in the induction of antibod y and CD8+ effector cells, may also play a direct role in protection a gainst sporozoite challenge by targeting EEF within the liver.