PHAGE-DISPLAYED MIMOTOPES ELICIT MONOCLONAL-ANTIBODIES SPECIFIC FOR AMALARIA VACCINE CANDIDATE

The phage-displayed peptide CGRVCLRC (C15) has been isolated from a ra ndom library by affinity screening with the D14-3 monoclonal antibody, which was raised to the 42 kDa C-terminal fragment of the major meroz oite surface protein 1 of Plasmodium vivax (Pv42). In order to investi gate the use of such mimotopes as possible Vaccine components, we stud ied the antibody response in Biozzi mice immunized with C15. High tite rs 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 anti bodies that specifically bind the Pv42 fragment were isolated. Althoug h these mAbs had a lower affinity for Pv42 when compared to D14-3, the y 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 c onformations of all three antibodies, but molecular modeling failed to reveal common structural features of their paratopes that could accou nt for their cross-reacting patterns. These data demonstrate that mimo topes selected from random repertoires do not necessarily represent st ructural equivalents of the original antigen but provide functional im ages that could replace it for vaccine development.