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

项目摘要 迫切需要针对新出现的小说制定有效的对策 冠状病毒或“新冠状病毒”(也称为新冠肺炎)。一种“通用”冠状病毒的研究进展 疫苗不仅对新冠肺炎有效，而且从理论上讲，还可以预防未来的疫情。 潜在的大流行性冠状病毒毒株。获得这样一种疫苗的途径可能会集中在设计新的 诱导针对保守的病毒表位的广谱中和抗体的免疫原，如受体 结合位点(RBS)。在这里，我们利用我们的基于结构的“表面处理”和葡聚糖工程 免疫基因设计通用流感疫苗的方法并将其扩展到新冠肺炎。我们正在进行的 对流感的研究表明，我们重新浮出水面的异源分子免疫原方法实质上 增加了引发RBS定向反应的总频率和我们的多糖工程方法 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；我们 设想为新冠肺炎具体实施可比的免疫原设计方法 聚焦于它的受体结合界面表位也会产生类似的结果。我们打算利用这个 行政副刊，以生成初步数据，以显示我们的方法对 新冠肺炎疫苗，并在小鼠模型中优化疫苗方案；这里产生的数据 将成为未来研究通用冠状病毒疫苗的基础。

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.