CELLULAR AND HUMORAL IMMUNE-RESPONSES TO WELL-DEFINED BLOOD-STAGE ANTIGENS (MAJOR MEROZOITE SURFACE-ANTIGEN) OF PLASMODIUM-FALCIPARUM IN ADULTS FROM AN INDIAN ZONE WHERE MALARIA IS ENDEMIC

Conserved and variant regions of two blood stage vaccine candidate ant igens of Plasmodium falciparum, merozoite surface antigen (MSA-1) and ring-infected erythrocyte surface antigen (Pf155/RESA), have been show n to be immunogenic. However, the relative immunogenicity of these imm unogens in different populations has not been studied. The conserved N -terminal region of MSA-1 was investigated for its immunogenicity by s tudying cellular (T cell) and humoral (B cell) immune responses in P. falciparum-primed individuals, living in malaria-hyperendemic areas (O rissa State, India), where malaria presents an alarming situation. MSA -l-derived synthetic peptides contained sequences that activated T cel ls to proliferate and release gamma interferon in vitro. There was con siderable variation in the responses to different peptides. However, t he highest responses (51% [18 of 35] by proliferation and 34% [12 of 3 5] by gamma interferon release) were obtained with a synthetic hybrid peptide containing sequences from conserved N- and C-terminal repeat r egions of MSA-1 and Pfl55/RESA, respectively. Antibody reactivities in an enzyme immunoassay of plasma samples from these donors to differen t peptides used for T-cell activation were heterogeneous. In general, there was poor correlation between DNA synthesis and either gamma inte rferon release or antibody responses in individual donors, underlining the importance of examining several parameters of T-cell activation t o assess the total T-cell responsiveness of a study population,to a gi ven antigen. However, the results from our studies suggest that synthe tic constructs containing sequences from the N- and C-terminal regions of MSA-1 and Pfl55/RESA representing different erythrocytic stages of the P. falciparum parasite are more immunogenic in humans living in m alaria-hyperendemic areas of India who have been primed by natural inf ection.