Phage-Displayed Mimotopes Elicit Monoclonal Antibodies Specific for a Malaria Vaccine Candidate - Archive ouverte HAL Access content directly
Journal Articles Biological Chemistry Year : 1998

Phage-Displayed Mimotopes Elicit Monoclonal Antibodies Specific for a Malaria Vaccine Candidate

Caroline Demangel
Sylvie Rouyre
  • Function : Author
Pedro M. Alzari
Farida Nato
  • Function : Author
Pierre Lafaye
Jean-Claude Mazie
  • Function : Author

Abstract

The phage-displayed peptide CGRVCLRC (C15) has been isolated from a random library by affinity screening with the D14-3 monoclonal antibody, which was raised to the 42 kDa C-terminal fragment of the major merozoite surface protein 1 of Plasmodium vivax (Pv42). In order to investigate the use of such mimotopes as possible vaccine components, we studied the antibody response in Biozzi mice immunized with C15. High titers of antibodies cross-reacting with Pv42 were generated and the IC50 of all immune sera were in the 5 x 10(-9) M range. Two monoclonal antibodies that specifically bind the Pv42 fragment were isolated. Although these mAbs had a lower affinity for Pv42 when compared to D14-3, they reproduced the cross-reactivity of D14-3 with the equivalent protein in P. cynomolgi, a close relative of P. vivax. DNA sequence analysis showed similarities between the germline genes and the canonical CDR conformations of all three antibodies, but molecular modeling failed to reveal common structural features of their paratopes that could account for their cross-reacting patterns. These data demonstrate that mimotopes selected from random repertoires do not necessarily represent structural equivalents of the original antigen but provide functional images that could replace it for vaccine development.

Dates and versions

pasteur-03136645 , version 1 (09-02-2021)

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Cite

Caroline Demangel, Sylvie Rouyre, Pedro M. Alzari, Farida Nato, Shirley Longacre, et al.. Phage-Displayed Mimotopes Elicit Monoclonal Antibodies Specific for a Malaria Vaccine Candidate. Biological Chemistry, 1998, 379 (1), pp.65-70. ⟨10.1515/bchm.1998.379.1.65⟩. ⟨pasteur-03136645⟩

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