Selection of HIV-specific immunogenic epitopes by screening random peptidelibraries with HIV-1-Positive sera

Efforts to develop a protective HIV-1 vaccine have been hindered by difficu lties in identifying epitopes capable of inducing broad neutralizing Ab res ponses. In fact, the high mutation rate occurring in HIV-1 envelope protein s and the complex structure of gp120 as an oligomer associated with gp41 re sult in a high degree of antigenic polymorphism. To overcome these obstacle s, we screened random peptide libraries using sera from HIV-infected subjec ts to identify antigenic and immunogenic mimics of HIV-1 epitopes, After ex tensive counterscreening with HIV-negative sera, we isolated peptides speci fically recognized by Abs from HIV-1-infected individuals. These peptides b ehaved as antigenic mimics of linear or conformational HIV-1 epitopes gener ated in vivo in infected subjects. Consistent with these findings, sera of simian HIV-infected monkeys also recognized the HIV-specific epitopes, The selected peptides were immunogenic in mice, where they elicited HIV-specifi c Abs that effectively neutralized HIV-1 isolates. These results demonstrat e that pools of HIV-1 mimotopes can be selected from combinatorial peptide libraries by taking advantage of the HIV-specific Ab repertoire induced by the natural infection.