A NOVEL PLASMODIUM-FALCIPARUM SPOROZOITE AND LIVER STAGE ANTIGEN (SALSA) DEFINES MAJOR-B, T-HELPER, AND CTL EPITOPES

In the search for subunit vaccines that are able to induce the type of sterile, protective immunity achieved by irradiated sporozoites, ther e is increasing evidence that defense mechanisms directed at the intra hepatic stage and Ags expressed at this stage are critical, We have in itiated a systematic search for such molecules and report here the ide ntification and partial characterization of a novel Plasmodium falcipa rum gene encoding a 70-kDa protein, expressed in both sporozoite and l iver stages (SALSA), with a vaccine potential that stems from its anti genic features, Antigenicity and immunogenicity studies were conducted in individuals exposed to malaria, in immunized mice, and in chimpanz ees, using a recombinant protein and two synthetic peptides, Results s how that the SALSA nonrepetitive sequence defines 1) major B cell epit opes, as shown by a high prevalence of Abs to each peptide in three Af rican areas differing in their level of endemicity; 2) Th epitopes, as demonstrated by lymphoproliferation and IFN-gamma secretion in cells from the individuals from one of the low transmission areas, as well a s helper effect upon Ab secretion in mice; and 3) epitopes for cytolyt ic lymphocytes, demonstrated in immunized and sporozoite-challenged ch impanzees, and associated with MHC class I leukocyte Ags, The latter a re of particular importance, because this is the only part of the mala ria life cycle in which the parasite is located in a cell expressing c lass I Ags and because CD8(+) lymphocytes were found to be responsible for protection in experimental models.