Immune responses against Plasmodium falciparum asexual blood-stage antigens and disease susceptibility in Gabonese and Cameroonian children

The frequency and level of cellular and humoral responses to seven syntheti c peptides from asexual blood stages of Plasmodium falciparum were measured in two cohorts of children living in areas highly endemic for malaria in G abon and Cameroon. A prospective longitudinal study was conducted for one y ear in these sites to examine the relationship between specific in vitro im mune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 [M SA-1] and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 [RAP-1] peptides) in the v illage of Dienga, Gabon. Higher response rates of interferon-gamma but lowe r response rates of tumor necrosis factor-alpha to four and six peptides, r espectively were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher p revalence rate in Dienga of the antibody responders to the peptide from Pf1 55/ring-infected erythrocyte surface antigen (RESA). Our results support th e inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pf155/RESA antigens i n a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical crit eria in two separate areas may lead to contrasting observations, demonstrat ing the geographic limitation of the interpretation of such results.