RECOGNITION BY HUMAN SERA AND IMMUNOGENICITY OF HBSAG MIMOTOPES SELECTED FROM AN M13 PHAGE DISPLAY LIBRARY

We used two mouse monoclonal antibodies (mAb) specific for the human h epatitis B virus surface antigen (HBsAg) to screen a random peptide li brary of 15 amino-acid residues displayed as a fusion to protein III o f filamentous phage M13. By a combination of affinity selection, immun e-screening and ELISA techniques, we selected peptides that are recogn ized by the anti-HBsAg mAb and show aa similarity with the natural ant igen. The selected phage-displayed epitopes (phagotopes) behave as ant igenic mimics of HBsAg. One phagotope is specifically recognized by hu man sera from HBsAg-immunized individuals, pointing to the possible us e of phagotopes as markers to detect the presence of specific Ab in th e serum. The same phagotope also elicits Ab directed against HBsAg in mice, indicating that mAb-selected phagotopes can also be immunogenic mimics of the natural antigen. These findings demonstrate that it is p ossible to identify disease-specific epitopes that can be used as diag nostic reagents and as leads for the development of acellular vaccines .