A longitudinal study was undertaken in Burkina Faso among 293 children aged 6 months to 9 years in order to determine the correlation between an antibody response to several individual malarial antigens and malarial infection. It was found that the presence of a positive antibody response at the beginning of the rainy season to three long synthetic peptides corresponding to Plasmodium falciparum Exp-1 101-162, MSP-3 154-249 and GLURP 801-920 but not to CSP 274-375 correlated with a statistically significant decrease in malarial infection during the ongoing transmission season. The simultaneous presence of an antibody response to more than one antigen is indicative of a lower frequency of malarial infection. This gives scientific credibility to the notion that a successful malaria vaccine should contain multiple antigens.

A polypeptide of 69 amino acids (PbCS 242–310) encompassing the C‐terminal region of the circumsporozoite protein of Plasmodium berghei (PbCS) was generated using solid‐phase peptide synthesis. The immunological and protective properties of peptide PbCS 242–310 were studied in BALB/c mice (H‐2d). Two subcutaneous injections, in the presence of IFA at the base of the tail, generated (i) high titers of anti‐peptide antibodies which also recognized the native P. berghei CS protein, (ii) cytolytic T cells specific for the Kd‐restricted peptide PbCS 245–253 and (iii) partial CD8+‐dependent protection against sporozoite‐induced malaria. The same frequencies of peptide PbCS 245–253 specific CD8+ T cells were found by IFN‐γ ELISPOT in the draining lymph nodes of animals immunized with the short optimal CTL peptide 245–253 or with the polypeptide 242–310, indicating that the longer polypeptide can be processed and presented in vivo in the context of MHC class I as efficiently as the short CTL peptide. Interestingly, higher levels of IFN‐γ producing CD8+ T cells and protection were observed when the four cysteine residues present in the C‐terminal peptide were fully oxidized. These findings underline the potential importance of the chemical nature of the C‐terminal fragment on the activation of the immune system and concomitant protection.

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The present work describes the recognition of three synthetic polypeptides encompassing the N- and C-terminal regions of the transmembrane Exp-1 protein of the parasite Plasmodium falciparum by plasma and peripheral blood mononuclear cells from naturally exposed individuals living in African endemic areas. The three polypeptides comprise the sequences 23-105, 73-162 and 101-162, and overlap at the transmembrane domain (73-105). Thus, they permitted characterization of the immune response specific to the N- and C-terminal domains in an independent fashion. Two different populations were evaluated, one in the village of Safo in Mali and the other in the villages of Somnaway, Kabortenga and Toussouktenga in Burkina Faso. Antibodies to the sequence 73-162 of Pf Exp-1 were found in 70% of adult Mali donors and in all of the donors tested from Burkina Faso. Strikingly, the N-terminal fragment Pf Exp-1 23-105 was only weakly recognized by a few donors. Evaluation of the T-cell response indicated that the peptide Pf Exp-1 23-105 was more potent than Pf Exp-1 73-162 in inducing a proliferative response. A correlation between peptide-specific interferon-gamma and interleukin-6 production and proliferation to peptide Pf Exp-1 23-105 was observed. Further studies are needed to evaluate this molecule as a vaccine candidate.

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