NOVEL ROUTES TO NATIVE OLIGOMERIC HIV1 ENVELOPE

天然寡聚 HIV1 包膜的新途径

• 批准号: 2555207
• 负责人: PAUL W PARREN
• 金额: $ 26.25万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2555207
• 关键词: HIV envelope protein gp120; HIV envelope protein gp160; HIV infections; SCID mouse; antiviral antibody; human immunodeficiency virus 1; human tissue; lymphocyte; microorganism immunology; monoclonal antibody; neutralizing antibody; surface antigens; virion

DESCRIPTION: One reason for the failure of subunit vaccine preparations is that they do not present native envelope epitopes efficiently. Immunogens such as HIV gp160 actually represent nonnative forms of the viral envelope (viral debris). It is possible that the abundance of the gp160 precursor protein even interferes with the maturation of the response to native envelope, which itself is a poor immunogen. If a novel strategy can be developed to obtain envelope immunogens targeted to stimulate a strong antibody response against native envelope and a decreased response to viral debris, protection against HIV-1 in hu-PBL-SCID mice would be achievable. There are 4 specific aims: 1) To define the quality of envelope-based immunogen using a set of monoclonal antibodies that distinguish between the native virion-associated gp120 and the nonnative viral debris gp160. 2) To improve processing of gp160 precursor in vitro and 3) to partition a large amount of envelope in its native configuration on the surface of cells or pseudovirions. 4) To transfer neutralizing antisera in hu-PBL-SCID mice in order to assess protection against HIV-1 in vivo.

描述：亚单位疫苗制备失败的一个原因是 它们不能有效地呈递天然包膜表位。 免疫原 例如HIV gp 160实际上代表了病毒包膜的非天然形式 （病毒碎片）。 有可能gp 160前体的丰度 蛋白质甚至干扰了对天然免疫应答的成熟。 包膜本身就是一种不良免疫原。 如果一个新的策略可以 开发以获得包膜免疫原，靶向刺激强烈的 对天然包膜的抗体应答和对病毒的应答降低 因此，在hu-PBL-SCID小鼠中针对HIV-1的保护将是可实现的。 具体目标有4个：1）确定基于网络的质量 免疫原使用一组单克隆抗体， 天然病毒体相关的GP 120和非天然病毒碎片GP 160。 2)到 改进体外gp 160前体的加工和3）将大的 细胞表面上天然构型的包膜量，或 假病毒体 4)将中和抗血清转移到hu-PBL-SCID小鼠中， 以评估体内对HIV-1的保护作用。