Synthetic vaccines and HIV-1 hypervariability: a "mixotope" approach

The hypervariability of the gp120 envelope protein principal neutralizing domain, the V3 loop, represents a major problem in the design of vaccines against HIV-1. We have designed a mixed V3 loop peptide, termed "mixotope," obtained in a unique synthesis, and containing around 7.5 x 10(5) different sequences of 22 to 25 residues, organized around the conserved GPGR tetrapeptide. Free or coupled to a carrier protein, the "mixotope" induced in rabbits broadly specific antibodies, which recognized different individual V3 loop sequences, and the native gp120 protein. The "mixotope" approach may allow researchers to focus vaccine strategy against hypervariable functional epitopes of various pathogens.