RECOMBINANT VIRUSES EXPRESSING A HUMAN MALARIA ANTIGEN CAN ELICIT POTENTIALLY PROTECTIVE IMMUNE CD8(+) RESPONSES IN MICE

Extensive studies on protective immunity to rodent malaria provided th e basis for thr current experiments in which mice mere immunized with recombinant (re) influenza and vaccinia viruses expressing selected se quences of the circumsporozoite (CS) protein of the human malaria para site Plasmodium falciparum, Mice of different H-2 haplotypes immunized with re influenza viruses expressing the immunodominant B cell epitop e of this CS protein produced high titers of antibodies to the parasit e, A cytotoxic T lymphocyte epitope of the CS protein of P. falciparum , PF3, recognized by CD8(+) T cells of H-2(k) mice, was expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf). Immunizat ion of mice with either FluPf or VacPf elicited a modest CS-specific C D8(+) T cell response detected by interferon gamma secretion of indivi dual immune cells, Priming of mice with FluPf, followed by a booster w ith VacPf, resulted in a striking enhancement of this T cell response, The reverse protocol, i.e., priming with VacPf followed by a booster with FluPf, failed to enhance the primary response. VacPf also greatly enhanced the primary response of mice injected with P. falciparum spo rozoites or with a lipopeptide containing PF3. A booster with FluPf al so amplified the response of lipopeptide- or sporozoite-primed mice bu t less than a VacPf booster did, Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administr ation of two distinct immunogens expressing PF3 elicited activated, ex travasating CS-specific T cells that protected against api intracerebr al VacPf challenge.