Immunogen Design for SARS-CoV-2

SARS-CoV-2峰值是大多数第一代COVID-19疫苗的基础，这些疫苗目前正在进行III期测试或刚刚获得FDA批准。 我们预期来自野生型或“2 P”稳定的刺突的免疫原性可能不是最佳的，并且目前正在努力改进。具体而言，我们和其他人正在努力定义SARS-CoV-2逃避体液免疫反应的基于尖峰的机制，并确定有效预防SARS-CoV-2感染的抗体。基于这一发展中的见解，我们正在使用抗体指导的基于结构的设计来开发基于刺突的免疫原，这些免疫逃避机制被禁用，以便优先引发有效的中和抗体。 我们还开始将这些基于刺突的免疫原与高免疫原性载体蛋白或自组装纳米颗粒偶联，因为多价展示通常产生比单个刺突三聚体高得多的免疫原性。

The SARS-CoV-2 spike is the basis of the majority of 1st-generation COVID-19 vaccines, which are currently in Phase III testing or just receiving FDA approval. We anticipate the immunogenicity from wild-type or "2P"-stabilized spikes may not be optimal, and are currently working to improve. In specific, we and others are working to define spike-based mechanisms by which SARS-CoV-2 evades the humoral immune response as well as to identify antibodies that are effective at preventing SARS-CoV-2 infection. Based on this developing insight, we are using antibody-guided structure-based design to develop spike-based immunogens with these immune-evading mechanisms disabled so as to preferentially elicit potently neutralizing antibodies. We have also begun to couple these spike-based immunogens to highly immunogenic carrier proteins or self-assembling nanoparticles, as multivalent display often yields substantially higher immunogenicity than that of a single spike trimer.