Cryo-ET of IgG bivalent binding on SARS-CoV-2 provides structural basis for antibody avidity

作者：Hangping Yao, Yutong Song, Qi Huang, Miaojin Zhu, J. Nellie Liang, Zheyuan Zhang, Xiaodi Zhang, Dongyang Dong, Danrong Shi, Zhigang Wu, Xiangyun Lu, Haibo Wu, Yong Chen, Sai Li · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-71631-5 · 被引用次数：5 · 研究领域：SARS-CoV-2 and COVID-19 Research、Monoclonal and Polyclonal Antibodies Research、Diabetes and associated disorders

The bivalent nature of IgG antibodies can enhance its neutralization potency against enveloped viruses; however, on-virion structural details of IgG bivalent binding with antigens remain elusive. Here we investigate how two potent IgGs P17 and S309 interact with S-trimers on the SARS-CoV-2 surface by cryo-ET. We find both IgGs exploit the mobility of S-trimers to form diverse configurations of S-IgG dimer-of-trimers, which oligomerize into higher-order patterns. Specifically, P17 stabilizes S-trimers into linear assemblies within minutes, whereas S309 primarily stabilizes S-trimer into circular assemblies that extend into lattice-like structures. Both assembly patterns effectively activate complement cascade. Additionally, both IgGs can facilitate inter-virion coupling through bivalent binding of opposing S-trimers, potentially enhancing immune recognition and clearance. These findings establish a structural framework for understanding IgG avidity in neutralizing enveloped viruses and offer valuable insights for antibody engineering and vaccine design.