Humoral and Cell-Mediated Immune Responses to the Plasmodium falciparum Antigens PF155/RESA and CS Protein: Seasonal Variations in a Population Recently Reexposed to Endemic Malaria

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Abstract
Resurgence of falciparum malaria occurred in the Central Highlands of Madagascar in the 1980s and the disease is currently hyperendemic. We determined the humoral and cellular responses to synthetic peptides reproducing the repeat sequences of 2 major Plasmodium falciparum antigens: the Pf155/RESA and the circumsporozoite (CS) protein. Blood samples from 83 subjects living in a rural community near Antananarivo were obtained at the beginning and the end of the transmission season. At enrollment, 40 subjects presenting with and 43 without blood parasites had similar T cell proliferative response and antibody level to all antigens tested. However, P. falciparum-infected individuals exhibited a decrease in the absolute number of T lymphocytes, due to a diminished number of CD8+ and natural killer lymphocytes. The number of CD4+ cells was similar in both groups. In the overall population, 45% of subjects had a T cell response to at least 1 RESA peptide (29–35% responding to a given peptide) and 35% to the CS protein peptide. Thirty-two percent of the donors presented with RESA antibodies and 23% had CS protein antibodies. After 20 weeks, at the end of the transmission season, cellular proliferative responses to all antigens markedly decreased as evidenced by a decrease of both the number of responders and mean stimulation indexes. Humoral response to RESA, as detected by erythrocyte membrane immunofluorescence (number of responders and mean antibody titers) markedly increased. Humoral responses to the CS protein and RESA peptides were similar. In this nonimmune population, suppression of the cellular response to RESA and CS protein peptides after repeated exposures to P. falciparum must be taken into account for the potential use of subunit vaccines in endemic areas.

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