NOVEL ROUTES TO NATIVE OLIGOMERIC HIV1 ENVELOPE

天然寡聚 HIV1 包膜的新途径

• 批准号: 2673192
• 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 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673192
• 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.

亚单位疫苗制备失败的一个原因是