HIV/SIV STRUCTURAL GENE VECTORS AS A LIVE HIV VACCINE

描述(改编自申请者摘要)：一位成功的HIV病毒感染者 疫苗必须诱导保护性的HIV特异性CTL反应。一个活着的- HIV减毒疫苗提供了一种很有希望的策略来增强HIV- 特异性CTL反应。艾滋病病毒的基因简单衍生品-L已经被 提出了一种安全的活体减毒艾滋病毒疫苗的新方法。这个 该项目基于一种假设，即感染艾滋病毒 结构基因载体(SGV)提供保护性免疫 感染不同毒株的艾滋病毒。SGV是独一无二的逆转录病毒 表达由HIV组成的具有复制能力的病毒的载体 结构蛋白，但缺乏与发病相关的HIV基因。 由于其独特的遗传结构，SGV是不依赖于TAT的 并构成复制HIV Gag、POT、env和最小补体 附属基因。SGV的复制提供了自然的呈现 HIV结构蛋白在抗原提呈细胞中的表达，这确保了 MHC-I和MHC-I对细胞免疫的最佳刺激作用 第二类陈述。有限的复制周期产生了基因 对诱导对不同毒株的免疫至关重要的变异体 HIV，但将有害插入或重组的机会降至最低 事件。HIV SGV是基于原型牛白血病病毒(BLV) 在两个BLV中具有感染性、免疫原性和无致病性SGV 动物模型。这项研究的总体目标是检验这一假设 SGV在代孕SIV猴体内具有传染性和免疫原性 艾滋病和B细胞淋巴瘤的模型。具体目标是：1)界定 有效的HIV辅助基因的最小组合 HIV SGV在培养细胞和原代细胞中的复制；2)发展 在培养和原代中高效复制的类似SIV SGV 3)检测SIV SGV的感染性和免疫原性 在猕猴模型中。

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.