Immunogenicity of a vaccine preparation representing the variable regions of the HIV type 1 envelope glycoprotein

Variability of the major antigenic sites of the envelope glycoprotein of HI V-1 constitutes a major problem in the formulation of effective vaccines. W e have prepared a synthetic peptide vaccine that represents the major hyper variable epitopes (V1 through V5) of the clade B HIV-1 envelope glycoprotei n (gp120), We refer to this preparation as variable epitope immunogen or VE I vaccine. This construct takes into consideration the type and frequency o f amino acid substitutions found at each epitope during the evolution of th e virus in individual patients and in the target population. Immunization o f mice, rabbits, and rhesus macaques with the VEI vaccine resulted in the i nduction of long-lasting, high-titered HIV-1 antibodies, including antibodi es that neutralize primary isolates. We also documented lymphocyte prolifer ative responses to the VEI vaccine, its individual components, analogs, and subtype-specific peptides representing the major hypervariable regions of HIV-1 gp120, Delayed-type hypersensitivity responses to these antigens mere also demonstrated in mice. Our results show that this vaccine is highly im munogenic and safe in animals. Our data suggest that this formulation could become an important component of combination vaccine approaches against HI V-1 and other antigenically variable pathogens.