Scientific Core Two

科学核心二

• 批准号: 10589644
• 负责人: Marie Pancera
• 金额: $ 48.47万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-30 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589644
• 关键词: Antibodies; Antibody Formation; Antibody Response; Antigens; B-Lymphocytes; Binding; Biochemical; Complement 4b; Complex; Cryoelectron Microscopy; Crystallization; Cyclic GMP; Electron Microscopy Facility; Enzyme-Linked Immunosorbent Assay; Epitopes; Glycoproteins; HIV-1; HIV-1 vaccine; Human; Immunization; In Vitro; Knock-in Mouse; Mammalian Cell; Maps; Membrane; Messenger RNA; Methodology; Methods; Monoclonal Antibodies; Production; RNA vaccine; Reagent; Recombinant Antibody; Recombinant Proteins; Recombinants; Resolution; Robot; Sarna; Structure; Universities; Vaccines; Validation; Washington; X-Ray Crystallography; design; env Gene Products; env Glycoproteins; interest; manufacture; nanoparticle; neutralizing antibody; 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 (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.

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，并且是免疫原料设计的重点。然而 各种重组（REC）ENVS不显示与某些BNAB的推断种系（GL）的可检测结合， 例如VRC01级BNAB，这是我们IPCAVD项目的重点。 Rec Envs能够绑定 GLVRC01 BNAB已被设计并诱导GLVRC01 BNAB的产生 免疫原子。在此IPCAVD中，我们建议确定自我扩增（SA）mRNA是否表达我们的种系 靶向426C.mod.Core Prime和HXB2.WT.Core增强免疫原，以分泌物为单位表示 纳米颗粒（-C4B）或膜锚定（GP160ΔCT）将启动VRC01 B细胞响应的成熟 在人类中。科学核心二将为科学项目一和第二提供高质量试剂 科学核心IPCAVD之一以及有关选定疫苗引起的关注点的结构信息 与他们的抗原复杂，以描绘其表位。这些信息将帮助我们更好地了解 与REC ENV免疫原子相比，SARNA构建体引起的B细胞反应。