REPRODUCING THE IMMUNE-RESPONSE AGAINST THE PLASMODIUM-VIVAX MEROZOITE SURFACE PROTEIN-1 WITH MIMOTOPES SELECTED FROM A PHAGE-DISPLAYED PEPTIDE LIBRARY

We have used phage display technology to identify peptides binding D14 -3, a monoclonal antibody raised against the M(r) 42 000 C-terminal fr agment of Plasmodium vivax merozoite surface protein 1 (PvMSP1). By sc reening a constrained hexapeptide library, seven independent clones bi nding D14-3 were isolated. The reactivity of D14-3 for these peptides was lower than for the natural antigen and the antibody binding was st rictly associated with the viral context and the peptide conformation. Sequence analysis showed that five of them shared homology with the M (r) 42 000 C-terminal fragment (Pv42) and therefore appears to identif y the D14-3 epitope. However, the other two peptides, while related to each other, did not correspond to any sequence in the Pv42 molecules. To evaluate their immunological interest, these phagotopes were injec ted into mice belonging to Balb/c, 1C57B1/6 and Biozzi strains. All an imals developed a strong immune response against phage particles but o nly Biozzi mice produced antibodies cross-reacting with Pv42. All phag otopes in Biozzi mice elicited a specific response against Pv42, even those sharing no sequence similarity with the antigen. Moreover, the a vidities of these immune sera and the polyclonal response against Pv42 were comparable, suggesting phagotopes could be used as components of a subunit vaccine based on the C-terminal fragment of MSP1. Copyright (C) 1996 Elsevier Science Ltd