Approaches to Synthetic Vaccines Design of Epitope-Containing Amphiphilic Peptides Matching the Antigenic Structure in the Native Protein

A general procedure for the design of synthetic vaccines with the retained conformational features of protein antigenic determinants is described. This new concept emerges from detailed studies on the relationship between primary sequence and secondary structure formation of synthetic peptides and takes advantage of the amphiphilic nature of epitope-containing peptide segments in the native protein to accomplish structural modifications. These segments, for example amphiphilic helices or β-sheets, are stabilized by the insertion of secondary structure-inducing amino-acid residues on the hydrophobic part of the peptide without affecting the spatial arrangement of functional residues on the hydrophilic side. The availability of amphiphilic peptides with tailor-made conformational properties, e.g. helices, β-sheets, and, moreover, assemblies of these blocks to structures of higher order (‘folding units’), allows the presentation and stabilization of continuous as well as discontinuous epitopes by this approach. This strategy is exemplified for the case of two discontinuous epitopes taken from lysozyme, which are matched to host molecules with adequate conformational features by the help of computer-assisted molecular modelling. The implications of this new concept for the design of synthetic vaccines are discussed with special emphasis to the important role of peptide synthesis and chemical structure modification.