Isolation of peptides that mimic epitopes on a malarial antigen from random peptide libraries displayed on phage

The ring-infected erythrocyte surface antigen (RESA) is a dense-granule pro tein of Plasmodium falciparum which binds to the cytoskeletal structure of the erythrocyte after parasite invasion. It is currently under trial as a v accine candidate. In an effort to characterize further the antibody respons es to this antigen, we have panned two independent libraries of random pept ides expressed on the surface of filamentous phage with a monoclonal antibo dy (MAI, 18/2) against RESA. One library consisted of a potentially constra ined 17-mer peptide fused with the gpVIII phage coat protein, and the other displayed an unconstrained 15-mer as a fusion with the minor phage coat pr otein gpIII. Several rounds of biopanning resulted in enrichment from both libraries clones that interacted specifically with MAb 18/2 in protein-blot ting and enzyme-linked immunosorbent assay experiments. Nucleotide sequenci ng of the random oligonucleotide insert revealed a common predominant motif : (S/T)AVDD. Several other clones had related but degenerate motifs. Thus, a monoclonal antibody against a malarial antigen can select common mimotope s from different random peptide libraries. We envisage many uses for this t echnology in malaria research.