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

项目摘要/摘要 广谱中和抗体很可能是HIV-1疫苗的重要组成部分。HIV-1 包膜糖蛋白(Env)是中和抗体的唯一靶点，一直是免疫原研究的焦点。 设计。然而，不同的重组(Rec)环境不显示可检测到的与推测的生殖系(IGL)的结合 某些bNAbs，如VRC01类bNAbs，这是我们HIVRAD项目的重点。支持接收环境 设计了与IGL VRC01结合的bNAbs，并在使用时诱导产生IGL VRC01 bNAbs 作为免疫原。然而，这些新的免疫原不足以诱导IGL VRC01的成熟。 类bNAb到其广泛的中和形式。在这次HIVRAD中，我们建议使用新的试剂作为 引导VRC01类bNAbs发展的免疫原。试剂和结构核心将提供 HIVRAD项目1-3的高质量试剂以及所描述的所有抗体的结构信息 并在这种HIVRAD(疫苗引发的或从幼稚的人或动物中获得)与其表位形成复合体。 这些信息将帮助我们更好地理解我们的新免疫原引发的B细胞反应，并将 协助我们改善我们的“优质助推”计划。

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.