Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes

The antigenic polymorphism of HIV-1 is a major obstacle in developing an ef fective vaccine. Accordingly, we screened random peptide libraries (RPLs) d isplayed on phage with antibodies from HIV-infected individuals and identif ied an array of HIV-specific epitopes that behave as antigenic mimics of co nformational epitopes of gp120 and gp41 proteins. We report that the select ed epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 M ID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in co ntrast to the naive and mock-immunized monkeys, four of five mimotope-immun ized monkeys experienced lower levels of peak viremia, followed by viral se t points of undetectable or transient levels of viremia and a mild decline of CD4(+) T cells, and were protected from progression to AIDS-like illness . These results provide a new approach to the design of broadly protective HIV-1 vaccines.