Epitope focusing to the receptor binding motif for a universal coronavirus vaccine

通用冠状病毒疫苗受体结合基序的表位

• 批准号: 10188307
• 负责人: Aaron Gregory Schmidt
• 金额: $ 39.03万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-22 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188307
• 关键词: 2019-nCoV; Administrative Supplement; Affect; Angiotensin Receptor; Antibodies; Antigens; Binding; Binding Sites; COVID-19; COVID-19 vaccine; Cells; Coronavirus; Cryoelectron Microscopy; Data; Development; Engineering; Epitopes; Frequencies; Future; Hemagglutinin; Immune response; Immunodominant Epitopes; Immunological Models; Influenza; Influenza Hemagglutinin; Lead; Masks; Molecular; Pathway interactions; Peptidyl-Dipeptidase A; Polysaccharides; Property; Proteins; Regimen; Research; Scaffolding Protein; Serum; Site; Structure; Surface; Testing; Vaccines; Viral; Virus; X-Ray Crystallography; base; data modeling; design; in vivo evaluation; mimicry; mouse model; neutralizing antibody; novel; novel coronavirus; pandemic disease; prevent; receptor; receptor binding; response; scaffold; theories; universal influenza vaccine; viral fitness

Project Summary There is urgent need for the development of effective countermeasures against the newly emerged novel coronavirus or “nCoV” (also known as COVID-19). The development of a “universal” coronavirus (CoV) vaccine would not only be effective against COVID-19 but, in theory, would protect against future, potential pandemic CoV strains. The pathway to such a vaccine will likely focus on the design of novel immunogens that elicit broadly neutralizing antibodies to conserved viral epitopes, such as the receptor binding site (RBS). Here we leverage our structure-based, “resurfacing” and glycan engineering immunogen design approaches for a universal influenza vaccine and extend it to COVID-19. Our ongoing studies for influenza demonstrate that our resurfaced, heterochimeric immunogen approach substantially increased the overall frequency of elicited RBS-directed responses and our glycan engineering approach could effectively focus the immune response to a novel, conserved influenza hemagglutinin epitope; we envision that implementing comparable immunogen design approaches for COVID-19 specifically focusing to its receptor-binding interface epitope would yield similar results. We intend to use this Administrative Supplement to generate preliminary data to show the efficacy of our approach for a COVID-19 vaccine, and to optimize the vaccine regimen in the murine model; the data generated here will form the basis for future studies for a universal CoV vaccine.

项目概要 针对新出现的小说，迫切需要制定有效的对策 冠状病毒或“nCoV”（也称为 COVID-19）“通用”冠状病毒 (CoV) 的发展。 疫苗不仅可以有效对抗 COVID-19，而且从理论上讲，可以预防未来的、 潜在的大流行性冠状病毒毒株的研发途径可能会集中在新型疫苗的设计上。 引发针对保守病毒表位（例如受体）的广泛中和抗体的免疫原 在这里，我们利用基于结构的“表面重塑”和聚糖工程。 我们正在进行通用流感疫苗的免疫原设计方法并将其扩展到 COVID-19。 针对流感的研究表明，我们重新出现的异嵌合免疫原方法在很大程度上 增加了引发 RBS 定向反应的总体频率和我们的聚糖工程方法 可以有效地将免疫反应集中在一种新的、保守的流感血凝素表位上； 设想针对 COVID-19 实施类似的免疫原设计方法 我们打算使用它的受体结合界面表位来产生类似的结果。 行政补充，用于生成初步数据，以显示我们的方法的有效性 COVID-19 疫苗，并优化此处生成的数据的疫苗方案； 将为未来通用冠状病毒疫苗的研究奠定基础。