IDENTIFY AND CLASSIFY HIV FOR AIDS VACCINES

识别和分类艾滋病毒以用于艾滋病疫苗

• 批准号: 3769108
• 负责人: JAY A LEVY
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3769108
• 关键词: AIDS; AIDS vaccines; CD4 molecule; HIV envelope protein gp120; antibody neutralization test; antiserum; cell mediated cytotoxicity; enzyme linked immunosorbent assay; gene expression; genetic manipulation; glycoproteins; guinea pigs; human immunodeficiency virus 1; immunogenetics; immunological substance; serotyping; virus antigen; virus assembly; virus classification; virus morphology; virus protein

The search for an AIDS vaccine has been complicated by the high degree of genetic variation that characterizes the Human Immuno-deficiency Virus (HIV). In a prototype study of 20 different HIV, we found that isolates could be grouped into four distinct classes according to their biological properties and their sensitivity to serum neutralization in vitro. To assess the potential number of independent serotypes among the HIV isolated in our laboratory, we propose to confirm these initial results and to evaluate other HIV. Antisera to isolates selected from the four neutralization-specific groups are now being produced in guinea pigs. The sera obtained thus far show reactivity to both viral recombinant gag and env proteins by indirect ELISA. These strain-specific antisera will be used in neutralization as well as cytotoxicity and plaque inhibition assays to extend further the serotypic classification of HIV. Based on the results of this prototype study, the serotyping of a larger number of biologically cloned HIV of various geographical origin and with different biological features will be undertaken. Subsequently, the purified envelope glycoprotein (gp120) of isolates representative of the different serotypes defined will be used to immunize guinea pigs to confirm the existence and to localize serotypic determinants on the HIV envelope. The HIV selected will be then be used for preparation (Dr. Steimer, Chiron Corporation; Dr. Luciw, UC Davis) and testing (Dr. Gardner, et al, UC Davis) of candidate vaccines in guinea pigs and Rhesus monkeys. The vaccine materials obtained in this manner can be utilized for efficacy study in chimpanzees (Dr. Eichberg, Southwest Foundation). The outcome of this proposed research will be important for the design and preparation of an effective vaccine for AIDS.

寻找艾滋病疫苗的搜索很复杂 特征人的遗传变异程度 免疫缺陷病毒（HIV）。 在20个原型研究中 不同的艾滋病毒，我们发现分离株可以分为四个 根据其生物学特性及其的不同类别 对体外血清中和的敏感性。 评估独立血清型的潜在数量 在我们的实验室中孤立的艾滋病毒，我们建议确认这些 初始结果并评估其他艾滋病毒。 抗血清与分离株 从四个中和特异性组中选择 在豚鼠中生产。 到目前为止获得的血清 对病毒重组插入和ENV蛋白的反应性 间接ELISA。 这些特异性抗血清将用于 中和以及细胞毒性和斑块抑制测定 为了进一步扩展艾滋病毒的血清型分类。 基于这项原型研究的结果， 各种地理学的生物克隆艾滋病毒的大量 起源和具有不同的生物学特征。 随后，纯化的包膜糖蛋白（GP120） 代表定义的不同血清型的分离株将是 用于免疫豚鼠以确认存在和 将血清型决定因素定位在HIV信封上。 艾滋病毒 然后选择将用于准备（Steimer，Chiron博士 公司; Luciw博士，UC Davis）和测试（Gardner博士，ET博士 Al，UC Davis）豚鼠和恒河猴中的候选疫苗 猴子。 以这种方式获得的疫苗材料可以是 用于黑猩猩的功效研究（Eichberg博士， 西南基金会）。 这项拟议研究的结果 对于有效的设计和准备很重要 艾滋病疫苗。