Malaria infections begin when an infected mosquito''s bite injects motile sporozoites, which circulate briefly, then invade the host''s liver cells and develop there. These pre-erythrocytic stages present extra-and intracellular targets for humoral and cellular effector mechanisms. The demonstration that sporozoite-immunized human volunteers could be protected against malaria challenge has led to research on sporozoite-induced protective immune mechanisms.

Our investigations for vaccine development focus on defining the T- and B-cell epitopes of a major sporozoite (CS) surface antigen, the circumsporozoite protein, and identifying new antigenic targets in the sporozoite and hepatic stages of the malaria parasite. We study the specificity, effector function, and lymphokine secretion of T-cell clones from sporozoite-immunized human volunteers, as well as primate and rodent hosts, to determine their role in the immune response to the malaria parasite''s pre-erythrocytic stages. These studies provide a rationale for incorporating T- and B-cell epitopes into synthetic peptide vaccines to induce high-level cellular and humoral immunity against the malaria parasite. We have recently completed Phase I studies in human volunteers to assay the safety and immunogenocity of synthetic and recombinant subunit vaccines based on minimal T and B cell epitopes of the Plasmodium falciparum CS protein. Phase II studies are in progress to assay protection in the peptide-immunized vaccinees when challenged with viable P. falciparum sporozoites.