HIV/SIV STRUCTURAL GENE VECTORS AS A LIVE HIV VACCINE

描述（改编自申请人摘要）：一个成功的HIV

DESCRIPTION (adapted from applicant's abstract): A successful HIV vaccine must induce a protective HIV-specific CTL response. A live- attenuated HIV vaccine provides a promising strategy to boost the HIV- specific CTL response. Genetically simple derivatives of HIV-l have been proposed as a novel approach to a safe live-attenuated HIV vaccine. The project is based on the hypothesis that infection with HIV structural genes vectors (SGV) provides protective immunity against infection with diverse strains of HIV. The SGV are unique retrovirus vectors that express replication-competent viruses composed of the HIV structural proteins, but lack HIV genes associated with pathogenesis. Because of their unique genetic structure, the SGV are Tat-independent and constitutively replicate HIV gag, pot, env, and a minimal complement of accessory genes. Replication of the SGV provides natural presentation of HIV structural proteins in antigen presenting cells, which assures optimal stimulation of cell-mediated immunity through MHC class I and class II presentation. Limited cycles of replication generate genetic variants important for induction of immunity against diverse strains of HIV, but minimize the chance of a deleterious insertion or recombination event. The HIV SGV are based on prototypic bovine leukemia virus (BLV) SGV that are infectious, immunogenic, and lack pathogenicity in two BLV animal models. The overall goal of this study is to test the hypothesis that SGV are infectious and immunogenic in the surrogate SIV monkey model for AIDS and B-cell Iymphoma. The specific aims are: 1) to define the minimal combination of HIV accessory genes necessary for efficient replication of HIV SGV in cultured and primary cells; 2) to develop similar SIV SGV that replicate efficiently in cultured and primary cells; 3) to evaluate the infectivity and immunogenicity of the SIV SGV in the macaque model.