Hypervariable epitope constructs as a means of accounting for epitope variability

Abstract Epitope variability is one of the greatest obstacles to development of synthetic peptide vaccines. Based on a recently described hypervariable epitope (aa 414–434) on the envelope glycoprotein (gp130) to simian immunodeficiency virus (SIV mac 142), we have developed a novel approach to account for epitope variability. We have prepared, in a single synthesis, a cocktail of peptides, designated a hypervariable epitope construct (HEC), which collectively represent all the in vivo variability seen in an epitope. The HEC represents permutations of amino acid substitutions found in the epitope and has been able to induce antibodies with enhanced binding to native SIV and broad immunoreactivity to related epitope analogues.