HUMAN T-CELL RECOGNITION OF SYNTHETIC PEPTIDES REPRESENTING CONSERVEDAND VARIANT SEQUENCES FROM THE MEROZOITE SURFACE PROTEIN-2 OF PLASMODIUM-FALCIPARUM

Merozoite surface protein 2 (MSP2) is a malaria vaccine candidate curr ently undergoing clinical trials. We analyzed the peripheral blood mon onuclear cell (PBMC) response to synthetic peptides corresponding to c onserved and variant regions of the FCQ-27 allelic form of MSP2 in Gha naian individuals from an area of hyperendemic malaria transmission an d in Danes without exposure to malaria. PBMC from 20-39% of Ghanaians responded to each of the peptides by proliferation and 29-36% had PBMC which produced interferon-gamma (IFN-gamma) in response to peptide st imulation. In Danes, then was no proliferation to two of the peptides and only PBMC from 5% of the individuals proliferated to the other thr ee peptides. IFN-gamma production was not detected to any peptide. In both Danes and Ghanaians in only a few instances was IL-4 detected in the PBMC cultures. Overall PBMC from 79% of the Ghanaians responded by proliferation and/or cytokine secretion to at least one of three pept ides tested, whereas responses were only observed in 14% of Danes (P = 0.002). These data suggest that the Ghanaians had expanded peripheral blood T-cell populations recognizing the peptides as a result of natu ral infection. The findings are encouraging for the development of a v accine based on these T-epitope containing regions of MSP2, as the pep tides were broadly recognized suggesting that they can bind to diverse HLA alleles and also because they include conserved MSP2 sequences. I mmunisation with a vaccine construct incorporating the sequences prese nt in these peptides could thus be expected to be immunogenic in a hig h percentage of individuals and lead to the establishment of memory T- cells, which can be boosted through natural infection. (C) 1997 Elsevi er Science B.V.