T-CELL IMMUNITY TO PEPTIDE EPITOPES OF LIVER-STAGE ANTIGEN-1 IN AN AREA OF PAPUA-NEW-GUINEA IN WHICH MALARIA IS HOLOENDEMIC

Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antige ns considered for inclusion in a multiantigen, multistage subunit vacc ine against falciparum malaria. We examined T-cell proliferation and c ytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living i n an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where m alaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma i nterferon (IFN-gamma) production driven by LSA1 peptides ranged from 3 4 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD 8(+) cells, and was dissociated from T-cell proliferation. The frequen cies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 8 4 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In c ontrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL -5 responses to LSA1 peptides were detected in only 18% of the subject s. These data show that T-cell immunity to epitopes in the N- and C-te rminal regions of LSA1 are common in persons living in this area of Pa pua New Guinea where malaria is endemic. The dominance of type 1 CD8 c ell IFN-gamma responses is consistent with a role for this T-cell popu lation in immunity to liver-stage Plasmodium falciparum in humans.