Immunogen Design for SARS-CoV-2

SARS-CoV-2疫苗是大多数第一代新冠肺炎疫苗的基础，目前这些疫苗正处于第三阶段测试或刚刚获得FDA的批准。 我们预计野生型或“2P”稳定的刺激物的免疫原性可能不是最佳的，目前正在努力改善。具体地说，我们和其他人正在努力确定基于尖峰的机制，通过这种机制，SARS-CoV-2逃避体液免疫反应，以及识别有效预防SARS-CoV-2感染的抗体。基于这一不断发展的见解，我们正在使用抗体引导的基于结构的设计来开发基于棘突的免疫原，禁用这些免疫逃避机制，以便优先诱导有效的中和抗体。 我们还开始将这些基于尖峰的免疫原偶联到高度免疫原性的载体蛋白或自组装纳米颗粒上，因为多价展示通常比单一尖峰三聚体产生更高的免疫原性。

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.