MULTIDIMENSIONAL NMR OF HIV NEUTRALIZING ANTIBODY

HIV中和抗体的多维核磁共振

• 批准号: 2430486
• 负责人: JACOB ANGLISTER
• 金额: $ 9.2万
• 依托单位: WEIZMANN INSTITUTE OF SCIENCE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430486
• 关键词: AIDS vaccines; HIV envelope protein gp120; antigen antibody reaction; antiviral antibody; human immunodeficiency virus 1; neutralizing antibody; nuclear magnetic resonance spectroscopy; protein structure

DESCRIPTION (Abapted from Applicant's Abstract) The V3 loop of gp120 is a major neutralizing determinant of HIV-1. Segments of V3 or its immediate vicinity form the binding site for the gp120 co-receptors on T-cells and macrophages and its sequence determines the phenotype of the virus. Antibody binding to V3 or deletion of V3 prevent virus fusion with the target cells, and thus abolishes infectivity. Neutralization of a variety of HIV-1 strains, including field isolates, have shown that serum obtained after immunization with antigens containing V3 peptides of different strains. Immunization with a "cocktail" of peptides may overcome the variability problem. Phase I clinical trials of candidate vaccines containing V3 peptides have been conducted in the US and in France. The principal aim of the research proposed here is to solve the three-dimensional structure of the 0.5b Fv complex with a V3 peptide, RP 135, using multi-dimensional NMR. These studies will provide the first structural information about V3 and will identify the residues that are important for binding to neutralizing antibodies and the residues that determine the conformation of V3. The structue of V3 will deomnatrate which residues can potentially interact with the co-receptor for gp120 on T-cells and macrophages and why certain positions are variable while others are more conserved. The structural information obtained in these studies should be helpful in designing optimal peptide immunogens to be used in a peptide based vaccine against HIV.

gp 120的V3环是一个环。 HIV-1的主要中和决定簇。 V3的片段或其直接片段 附近形成T细胞上gp 120共受体的结合位点， 巨噬细胞和它的序列决定了病毒的表型。 与V3结合的抗体或V3的缺失阻止病毒与V3融合。 靶细胞，从而消除感染性。 品种的中和 的HIV-1菌株，包括田间分离株，已经表明， 在用含有不同的V3肽的抗原免疫后， 菌株 用肽的“鸡尾酒”免疫可以克服免疫缺陷。 可变性问题。 候选疫苗的I期临床试验 在美国和法国进行了含有V3肽的试验。 的 本研究的主要目的是解决 0.5b Fv与V3肽RP复合物的三维结构 135，使用多维NMR。 这些研究将首次提供 关于V3的结构信息，并将鉴定 对于结合中和抗体和 确定V3的构象。 V3的结构将分解， 残基可以潜在地与T细胞上的gp 120的共受体相互作用 以及为什么某些位置是可变的，而另一些位置 保守的 在这些研究中获得的结构信息应该是 有助于设计用于肽的最佳肽免疫原 预防艾滋病毒的疫苗。