Scientific Core Two

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信封 (Env)糖蛋白是中和抗体的唯一靶点，一直是免疫原设计的焦点。还没有 不同的重组(Rec)环境不显示可检测到的与某些bNAb的推测胚系(G1)的结合， 例如VRC01类bNAb，这是我们IPCAVD项目的重点。能够绑定的REC ENV 已经设计并诱导了glVRC01 bNAbs的产生，当用作 免疫原。在这个IPCAVD中，我们建议确定是否自我放大(Sa)mRNA表达我们的生殖系- 靶向426c.Mo.Core Prime和HxB2.WT.Core Boost免疫原，表达为分泌型 纳米粒(-C4b)或膜锚定的(gp160ΔCT)将启动VRC01B细胞反应的成熟 在人类身上。科学核心二号将为科学项目一和二提供高质量的试剂，并 IPCAVD的科学核心之一以及关于选定的疫苗引发的感兴趣的单抗的结构信息 在与它们的抗原的复合体中，描绘它们的表位。这些信息将帮助我们更好地理解 与rec Env免疫原相比，SARNA构建物所激发的B细胞反应。

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 (gl) of certain bNAbs, such as the VRC01-class bNAbs, which are the focus of our IPCAVD project. Rec Envs capable of binding glVRC01 bNAbs have been designed and induced the production of glVRC01 bNAbs when used as immunogens. In this IPCAVD, we propose to determine if self-amplifying (sa) mRNA expressing our germline- targeting 426c.Mod.Core prime and HxB2.WT.Core boost immunogens, expressed either as secreted nanoparticles (-C4b) or membrane-anchored (gp160ΔCT), will initiate the maturation of VRC01 B cell response in humans. The Scientific Core Two will provide high quality reagents to Scientific Projects One and Two and Scientific Core One of this IPCAVD as well as structural information on selected vaccine-elicited Mab of interest in complex with their antigens, to delineate their epitopes. This information will help us to better understand the B cell response elicited by the saRNA constructs compared to rec Env immunogens.