Synthetic Peptide Vaccines and the Search for Neutralization B Cell Epitopes#

ABSTRACT

Most attempts to develop synthetic peptide vaccines assume that it is possible to obtain effective vaccine immunogens by making short linear peptides adopt the structures observed when epitopes of pathogens are bound to neutralizing antibodies. Although more than a thousand synthetic peptides have been examined as potential prophylactic vaccines, only 125 peptides have progressed to phase I clinical trials, 30 have made it to phase II trials but not a single one has passed phase III trials and is currently marketed for human use.

Reasons for this lack of success include 1) an excessive reliance on continuous epitopes as vaccine candidates, 2) an exaggerated confidence in the specificity of antibodies, 3) the failure to recognize that an operational bias is introduced when monoclonal antibodies are used to characterize epitopes and, 4) a tendency to underestimate the difference between antigenicity and immunogenicity. There clearly is a need to overcome these misconceptions if synthetic peptide vaccines are ever to become a reality.

Keywords:

Antigenicity, epitope prediction, immunogenicity, HIV, mimotopes, monoclonal antibodies, peptide-based vaccines.