Epitope variability is one of the greatest obstacles to development of
synthetic peptide vaccines. Based on a recently described hypervariab
le epitope (aa 414-434) on the envelope glycoprotein (gp130) to simian
immunodeficiency virus (SIVmac142), we have developed a novel approac
h to account for epitope variability. We have prepared, in a single sy
nthesis, a cocktail of peptides, designated a hypervariable epitope co
nstruct (HEC), which collectively represent all the in vivo variabilit
y seen in an epitope. The HEC represents permutations of amino acid su
bstitutions found in the epitope and has been able to induce antibodie
s with enhanced binding to native SIV and broad immunoreactivity to re
lated epitope analogues.