SYNTHETIC PEPTIDES TO DEVELOP SIMIAN RETROVIRAL VACCINE

用于开发猴逆转录病毒疫苗的合成肽

• 批准号: 3143153
• 负责人: ARTHUR MALLEY
• 金额: $ 13.91万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3143153
• 关键词: AIDS; AIDS vaccines; Macaca mulatta; Retroviridae; T lymphocyte; cell mediated cytotoxicity; cellular immunity; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; epitope mapping; hemocyanin; human immunodeficiency virus; interleukin 1; laboratory mouse; monoclonal antibody; neutralizing antibody; simian AIDSs; simian virus; viral vaccines; virus antigen; virus envelope; virus receptors

The insoluble SRV-2 envelope peptide 88-103 specifically binds rhesus anti- SRV-2 neutralizing antibodies. SRV-2 peptide 97-103 appears to the epitope that induces potential T cell activating properties of SRV-2 peptide 88-95, SRV-1 and SRV-2 envelope peptides shared by both virus. SRV-1 and SRV-2 peptide-KLH conjugates will be used to induce rhesus anti-envelope peptide neutralizing antibodies. These antibodies will be tested for their ability to block syncytium formation of virus in vitro, and when the rhesus monkeys make significant levels of SRV-1 or SRV-2 neutralizing antibody the animals will be challenged with the live SRV-1 or SRV-2 virus. SRV-1 or SRV-2 envelope peptides will be used to define epitopes involved in virus specific cytotoxic T lymphocyte (CTL) and/or antibody dependent cellular cytotoxicity (ADCC) responses. Characterization of epitopes associated with epitopes involved in CTL and ADCC responses will permit us to explore immunization protocols that might enhance virus-specific CTL and ADCC responses. Rhesus monkeys having enhanced CTL and/or ADCC responses may permit the development of virus-specific CTL cell lines and determine the role of CTL and/or ADCC responses in the protection against SRV-1 or SRV-2 virus infection. A NP40 extract of Raji cells will be used to isolate the receptor for virus binding. Affinity adsorbents prepared from SRV-1 peptide 150-157 or gp 70 will be used to isolate the putative receptor. Analysis of the receptor for virus binding will include 1) ability to block syncytial formation of virus growth in Raji cells, 2) direct binding of radiolabeled receptor with SRV-1 and/or SRV-2 virus, and 3) inhibition of radiolabeled peptide interaction with SRV-1 and/or SRV-2 virus. The isolated receptor will be used to prepare polyclonal and monoclonal anti-receptor antibodies. Our long term goal is to define SRV-1 and SRV-2 envelope peptides that can be used to induce enhanced neutralizing antibodies and/or CTL and ADCC virus-specific responses that can provide a vaccine to protect nonhuman primates from retroviral infections. The availability of isolated receptor and anti-receptor antibodies will be used to study virus-host cell interactions and define the range of cells that can be infected by virus.

不溶性SRV-2被膜肽88-103与恒河猴抗-2抗体特异性结合 SRV-2中和抗体。SRV-2多肽97-103出现在表位 诱导SRV-2肽88-95的潜在T细胞激活特性， SRV-1和SRV-2的囊膜多肽是两种病毒共有的。SRV-1和SRV-2 多肽-KLH偶联物将用于诱导恒河猴抗包膜多肽 中和抗体。这些抗体将被测试它们的能力 在体外阻断合胞体病毒的形成，并在恒河猴 使动物产生显著水平的SRV-1或SRV-2中和抗体 将受到活的SRV-1或SRV-2病毒的挑战。 将使用SRV-1或SRV-2包膜多肽来定义所涉及的表位 病毒特异性细胞毒性T淋巴细胞(CTL)和/或抗体依赖 细胞毒性(ADCC)反应。表位的表征 与CTL和ADCC反应中涉及的表位相关联将允许我们 探索可能增强病毒特异性CTL和 ADCC响应。CTL和/或ADCC反应增强的恒河猴 可能允许开发病毒特异的CTL细胞系并确定 CTL和/或ADCC应答在预防SRV-1或 SRV-2病毒感染。 Raji细胞的NP40提取物将用于分离病毒的受体 有约束力的。SRV-1多肽150-157或GP 70亲和吸附剂的制备 将被用来分离可能的受体。受体的分析 用于病毒结合将包括1)阻止合胞体形成的能力 病毒在Raji细胞中的生长，2)放射性标记受体与 SRV-1和/或SRV-2病毒；3)放射性标记多肽的抑制作用 与SRV-1和/或SRV-2病毒的相互作用。分离的受体将是 用于制备多克隆和单克隆性抗受体抗体。 我们的长期目标是定义SRV-1和SRV-2包膜多肽 用于诱导增强的中和抗体和/或CTL和ADCC 病毒特异性反应，可提供疫苗保护非人类 灵长类动物免受逆转录病毒感染。分离受体的可用性 抗受体抗体将被用来研究病毒宿主细胞 相互作用并定义可被病毒感染的细胞范围。