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.

项目摘要/摘要 广泛中和抗体可能是HIV-1疫苗的重要组成部分。 HIV-1 信封（Env）糖蛋白是中和抗体的唯一靶标，并且一直是免疫原的重点 设计。然而，多样化的重组（REC）ENV并未显示可检测到的与推断的种系（IgL）的结合 某些BNAB，例如VRC01级BNAB，这是我们Hivrad项目的重点。 Rec Envs有能力 使用时已经设计并诱导IGL VRC01 BNAB的产生Igl VRC01 BNAB的结合Igl 作为免疫原子。但是，这些新型免疫原不足以诱导IGL VRC01-的成熟 bnabs的范围为其广泛的神经化形式。在此Hivrad中，我们建议将新型试剂用作 免疫原子指导VRC01级BNAB的发展。试剂和结构核心将提供 HIVRAD项目1-3的高质量试剂以及有关所有抗体的结构信息 并在与其表位的复合物中获得的Hivrad（疫苗吸收或幼稚的人或动物）获得。 这些信息将帮助我们更好地理解我们新颖的免疫原子引起的B细胞响应，并将 协助我们改善我们的“ Prime-nof-to-the”计划。