Crossreactivity of mimotopes and peptide homologues of a sequential epitope with a monoclonal antibody does not predict crossreactive immunogenicity

The sequence H236-256 of the measles virus (MV) hemagglutinin (H) contains the sequential epitope of the neutralizing and protective monoclonal antibo dy (mAb) BH129 with the minimal epitope E245L-QL(249) Using this mAb, we ha ve recently developed 7mer mimotopes binding up to 135x better than the cor responding 7mer epitope H244-250. In this study, we combined T cell epitope s (TCE) with either highly crossreactive 7mer mimotopes, 13mer mimotopes or less crossreactive MV-derived B cell epitopes (ECE). Antigenicity of these TBB, TTB and TTBB peptides was determined with BH129 in a competition ELIS A against MV. We found that chimeric peptides including mimotopes were up t o 80x better binders to the mAb than peptides containing the original BCEs. All peptides irrespective of their antigenicity were used for immunization to compare their virus- crossreactive immunogenicity. Unexpectedly, none o f the highly antigenic mimotope-based peptides induced MV-crossreactive ant ibodies. In contrast, a number of peptides with the viral BCE sequence that did not bind to the mAb,induced MV-crossreactive and even neutralizing ant ibodies. This report describes a striking example of disparity between antigenicity and crossreactive immunogenicity and casts considerable doubt on the predic tive value of antigenicity in immunogenicity studies, considerably complica ting the selection of potential vaccine candidates. (C) 1999 Elsevier Scien ce Ltd. All rights reserved.