Synthetic polypeptides corresponding to the non-repeat regions from the circumsporozoite protein of Plasmodium falciparum: recognition by human T-cells and immunogenicity in owl monkeys.
Synthetic polypeptides encompassing the non-repeated regions of the circumsporozoite protein (CSP) of Plasmodium falciparum are very immunogenic in mice and are recognized by sera from donors living in regions where malaria is endemic, both in Africa and South America. Long polypeptides, encompassing the N- or C-terminal regions, have now been used to demonstrate peptide-specific T cells in donors living in an endemic area of Colombia. Although the N-terminal peptide (22-125) was recognized almost exclusively by donors from the endemic area, the patterns of recognition of the C-terminal peptide (289-390) in donors from endemic and non-endemic areas were similar and like the pattern with smaller peptides. The availability of the long polypeptides made it possible to compare T-cell responses to the non-repeated regions of the CSP with the presence of peptide-specific antibodies. No correlation was found and no antibodies were detected in donors from non-endemic regions. The long polypeptides also elicited strong antibody and T-cell responses in owl monkeys (Aotus lemurinus). The antibodies generated against the synthetic peptides in such monkeys also recognized sporozoites, the natural infective form of the parasite. The results emphasise the potential of the peptides tested as malaria-vaccine candidates. Not only are they recognized by humans at both the B- and T-cell level but they also elicit strong responses in monkeys and encompass several distinct T-cell epitopes, thus overcoming the limitations of specific, major-histocompatibility-complex restriction.
López
J A
JA
Institut de Biochimie, Université de Lausanne, Switzerland. alopez@ulrec1.unil.ch
González
J M
JM
Kettner
A
A
Arévalo-Herrera
M
M
Herrera
S
S
Corradin
G
G
Roggero
M A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D016645:Aotidae; D002478:Cells, Cultured; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007114:Immunization / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015800:Protozoan Proteins