T-CELL AND B-CELL RESPONSES OF MALARIA IMMUNE INDIVIDUALS TO SYNTHETIC PEPTIDES CORRESPONDING TO NON-REPEAT SEQUENCES IN THE N-TERMINAL REGION OF THE PLASMODIUM-FALCIPARUM ANTIGEN PF155 RESA/

While the C-terminal repeat region of Pfl55/RESA, a Plasmodium falcipa rum vaccine candidate has been extensively studied for B-and T-cell re activities, little is so far known about the non-repeat region in this respect. The present study aimed at investigating the non-repeat sequ ence 171-227 of Pfl55/RESA for T-and B-cell epitopes. Eight overlappin g peptides were synthesised and assayed for their ability to stimulate peripheral blood mononuclear cells obtained from P, falciparum-immune donors to proliferate and to induce secretion of interferon-gamma (IF N-gamma) and/or interleukin 4 (IL-4) using the ELISPOT assay. The plas mas of the corresponding donors were tested for antibody reactivity wi th the same peptides in ELISA. The individual cellular responses to th e different peptides varied and in general they were not correlated, e mphasising the importance of including several parameters for T-cell a ctivation. The most frequent T-cell responses (proliferation, IFN-gamm a and/or IL-4) were seen with two partially overlapping peptides corre sponding to the sequences 171-185 and 181-195 that induced responses i n 71 and 62% of the donors, respectively. Although, the frequency of r esponders was high, the magnitude of the responses was generally low. Two overlapping peptides corresponding to the sequence 186-?206 bound antibodies from a large number of plasma samples. IL-4 producing cells were frequently found in donors whose sera contained antibodies to th e corresponding peptide. However, there was no absolute correlation an d many donors having anti-peptide antibodies could also be induced to produce IFN-gamma. In conclusion, the non-repeat region of Pf155/RESA contains several epitopes inducing functionally distinct T-cell respon ses. The sequence 171-206 was found to contain both B- and T-cell epit opes recognised by almost all individuals naturally primed to malaria. Thus, this sequence should be a useful tool in future immuno-epidemio logical studies and!or for inclusion into a subunit vaccine against th e asexual blood stages of the P, falciparum parasite. (C) 1997 Elsevie r Science B.V.