Core C: Viral Evolution

项目摘要-核心C：病毒进化 病毒进化核心将开发工具，为疫苗工程提供信息，这些疫苗广泛针对 构成大流行风险的冠状病毒。为了做到这一点，核心将使用深度突变扫描来定义 肉瘤病毒整个进化过程中RBDS和SPAKS的生化和功能特性 和分枝杆菌病毒，并系统地绘制这些蛋白是如何被疫苗引发的抗体靶向的 豁免权。在第一个目标中，我们将测量所有已知的肉瘤病毒和 识别感兴趣的关键毒株并为动物模型的发展提供信息的汞病毒rbds(核心B： 病毒学，巴里克)。在第二个目标中，我们将开发一个系统来测量所有突变是如何从 关键菌株影响细胞进入，从而识别功能受限的表位作为疫苗的靶标。在 第三个目标，我们将使用RBD和SPEKE文库来量化结合广度和对突变的稳健性 疫苗引发的单抗和多克隆抗体，从而提供直接的功能读数快速 评估候选疫苗，并告知其进一步的工程设计。

PROJECT SUMMARY – CORE C: VIRAL EVOLUTION The Viral Evolution Core will develop tools to inform the engineering of vaccines that broadly target coronaviruses that pose a pandemic risk. To do this, the core will use deep mutational scanning to define the biochemical and functional properties of RBDs and spikes across the full evolutionary span of sarbecoviruses and merbecoviruses, and systematically map how these proteins are targeted by vaccine-elicited antibody immunity. In the first aim, we will measure the receptor-binding properties of all known sarbecovirus and merbecovirus RBDs to identify key strains of interest and inform the development of animal models (Core B: Virology, Baric). In the second aim, we will develop a system to measure how all mutations to the spikes from key strains affect cell entry, thereby identifying functionally constrained epitopes to target with vaccines. In the third aim, we will use the RBD and spike libraries to quantify the binding breadth and robustness to mutations of vaccine elicited monoclonal and polyclonal antibodies, thereby providing direct functional readouts to rapidly assess candidate vaccines and inform their further engineering.