The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however, represents a major challenge. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.
NCI researchers used conserved elements (CEs) of the polypeptide Gag as an immunogenic composition to induce an immune response to HIV-1. This invention is based, in part, on the discovery that the administration of one or more polypeptides comprising seven CEs of HIV Gag provides a robust immune response compared to administration of a full-length Gag protein. In vivo studies of rhesus macaques vaccinated with variants of these constructs elicited strong, cellular T-cell and humoral antibody immune responses. The Gag-specific antibody responses were high titer and cross-clade.
A robust increase in immunity was observed when rhesus macaques were subjected to a prime-boost protocol. Rhesus macaques primed with Gag-CE DNA and boosted with full length Gag had increased cellular and humoral responses. The CE vaccines described in this invention are potential prophylactic and therapeutic HIV vaccines.