IDENTIFICATION OF T-CELL AND B-CELL EPITOPES RECOGNIZED BY HUMANS IN THE C-TERMINAL 42-KDA DOMAIN OF THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN (MSP)-1

The 42-kDa, C-terminal region of the merozoite surface protein-1 (MSP- 1) of Plasmodium falciparum is a putative malaria vaccine candidate Ag . Nine synthetic peptides corresponding to predicted T cell sites of M SP-1 in blocks 15 and 16 and eight overlapping peptides representing t he conserved block 17 were used to identify naturally immunogenic epit opes. These peptides were tested for their ability to induce prolifera tion of PBMC from residents in western Kenya, where malaria transmissi on is holoendemic. Six peptides (PL145, PL146, PL147, PL148, PL149, an d PL150) from blocks 15 and 16 induced a positive proliferative respon se in >30% of the individuals tested, and three peptides (PL151, PL152 , and PL153) induced a proliferative response in <25% of the donors. A mong these peptides, PL146 was from the highly conserved region, PL150 was from a polymorphic region, and all other peptides were from a dim orphic region of blocks 15 and 16. In block 17, only three peptides, P L99, PL100, and PL103, induced proliferation in 30 to 37% of the volun teers. The rest of the peptides induced a proliferative response in ap proximately 13 to 25% of the donors. The plasma from these donors wide ly reacted with different allelic forms of 19-kDa recombinant proteins representing block 17 and recognized at least two linear B epitopes, PL104 and PL97. In summary, this study revealed that a majority of imm unodominant T and B epitopes are localized in the conserved or dimorph ic regions that are nonpolymorphic in the 42-kDa protein of MSP-1. Thi s study suggests that incorporation of T epitopes from the dimorphic b locks 15 and 16 in a vaccine construct may be useful to ensure Ag-spec ific memory responses.