CD4 BINDING SITE ON HIV1 GP120 AS A VACCINE ANTIGEN

作为疫苗抗原的 HIV1 GP120 上的 CD4 结合位点

基本信息

批准号：
6170678
负责人：
MARTIN TEINTZE
金额：
$ 6.95万
依托单位：
MONTANA STATE UNIVERSITY - BOZEMAN
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-04-01 至 2002-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6170678
关键词：
AIDS vaccines CD4 molecule HIV envelope protein gp120 X ray crystallography chemical binding chimeric proteins molecular cloning neutralizing antibody nuclear magnetic resonance spectroscopy peptide chemical synthesis peptide library plant virus protein sequence recombinant virus vaccine development virus antigen

项目摘要

DESCRIPTION (adapted from applicant's abstract): Design of an effective vaccine against HIV must take into account the high degree of variability in the sequence of the envelope proteins that have been observed in clinical isolates, and the high mutation rate of the virus. The envelope glycoprotein gpl20 and its precursor gpl60 have been ineffective against clinical isolates of HIV when used as vaccine candidates. HIV-neutralizing antibodies are elicited primarily against the third variable (V3) loop of the sequence. Late in HIV infection, however, neutralizing antibodies with broader strain specificity are produced which appear to be directed at the three-dimensional shape of the CD4 binding site. The investigators hypothesize that this part of gpl20 will make a more effective vaccine antigen than the whole protein. They therefore plan to construct recombinant or synthetic molecules that display this conformation-dependent structure. Their immediate goals are to 1) better define those portions of gpl20 that are involved in binding to CD4; 2) express these gpl20 sequences as part of fusion proteins on the surface of a plant virus and determine which constructs can display the native conformation required for CD4 binding; 3) synthesize the sequences as peptides and model the three-dimensional structure of the CD4 binding epitope using NMR techniques. The structural information obtained from these studies and X-ray crystallography of the recombinant viruses may lead to the design of better recombinant or synthetic antigens that can elicit a more effective immune response to the virus.

描述（改编自申请人的摘要）：有效的设计艾滋病毒疫苗必须考虑到病毒的高度变异性临床中观察到的包膜蛋白序列且病毒突变率高。信封糖蛋白 gpl20 及其前体 gpl60 对抗病毒无效用作候选疫苗时的 HIV 临床分离株。 HIV中和主要针对第三个变量 (V3) 环引发抗体顺序。然而，在艾滋病毒感染后期，中和抗体产生了更广泛的菌株特异性，这似乎是针对 CD4结合位点的三维形状。调查人员假设 gpl20 的这一部分将成为更有效的疫苗抗原高于全蛋白。因此他们计划建造显示这种构象依赖性的重组或合成分子结构。他们的近期目标是 1）更好地定义参与与 CD4 结合的 gpl20； 2) 表达这些gpl20序列作为植物病毒表面融合蛋白的一部分并确定哪些构建体可以显示 CD4 所需的天然构象绑定； 3) 将序列合成为肽并建模使用 NMR 技术观察 CD4 结合表位的三维结构。从这些研究和 X 射线中获得的结构信息重组病毒的晶体学可能有助于设计更好的病毒重组或合成抗原可以引发更有效的免疫对病毒的反应。