Recombinant HIV-1 Env glycoprotein immunogens and antibodies production and structural characterization

重组 HIV-1 Env 糖蛋白免疫原和抗体的产生和结构表征

• 批准号: 10540728
• 负责人: Marie Pancera
• 金额: $ 32.05万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-06 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540728
• 关键词: Animals; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; Binding; Biochemical; Complex; Cryoelectron Microscopy; Crystallization; Data; Development; Epitopes; Glycoproteins; HIV-1; HIV-1 vaccine; Home; Human; Immune response; Immunoglobulin G; Immunoglobulin Idiotypes; Knock-in Mouse; Mammalian Cell; Maps; Monoclonal Antibodies; Mus; Production; Proteins; Reagent; Recombinants; Resolution; Robot; Roentgen Rays; Scheme; Source; Structure; Synchrotrons; Universities; Vaccines; Validation; Washington; X-Ray Crystallography; design; env Glycoproteins; improved; interest; large scale production; neutralizing antibody; novel; plasmid DNA; protein complex; response

PROJECT SUMMARY/ABSTRACT Broadly neutralizing antibodies are likely to be an important component of an HIV-1 vaccine. The HIV-1 Envelope (Env) glycoprotein is the sole target of neutralizing antibodies and has been a focus of immunogen designs. Yet diverse recombinant (rec) Envs do not display detectable binding to the inferred germline (iGL) of certain bNAbs, such as the VRC01-class bNAbs, which are the focus of our HIVRAD project. Rec Envs capable of binding iGL VRC01 bNAbs have been designed and induced the production of iGL VRC01 bNAbs when used as immunogens. However these novel immunogens are not sufficient to induce the maturation of iGL VRC01- class bNAbs to their broad neutralization forms. In this HIVRAD, we propose to use novel reagents as immunogens to guide the development of VRC01-class bNAbs. The Reagents and Structural Core will provide high quality reagents to Projects 1-3 of this HIVRAD as well as structural information on all antibodies described and obtained in this HIVRAD (vaccine-elicited or from naïve humans or animals) in complex with their epitopes. This information will help us to better understand the B cell response elicited by our novel immunogens and will assist us in improving our “prime-boost” schemes.

项目总结/摘要 广泛中和抗体可能是HIV-1疫苗的重要组成部分。的HIV-1 包膜糖蛋白（Env）是中和抗体作用的唯一靶点，已成为免疫原研究的热点 的设计.然而，不同的重组（rec）Env不显示与以下的推断的种系（iGL）的可检测的结合： 某些bNAb，如VRC 01类bNAb，这是我们HIVRAD项目的重点。支持录制环境 设计了结合iGL VRC 01 bNAb的抗体，并在使用时诱导iGL VRC 01 bNAb的产生 作为免疫原。然而，这些新的免疫原不足以诱导iGL VRC 01的成熟。 将bNAb类转化为其广泛的中和形式。在这个HIVRAD中，我们建议使用新的试剂， 免疫原来指导VRC 01类bNAb的开发。试剂和结构核心将提供 高质量的试剂，以项目1-3的艾滋病毒，以及结构信息的所有抗体描述 并且在该HIVRAD（疫苗引发的或来自幼稚的人或动物）中与它们的表位复合获得。 这些信息将帮助我们更好地了解我们的新型免疫原引起的B细胞反应， 协助我们改进我们的“prime-boost”计划。