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

Yao, Hangping; Song, Yutong; Huang, Qi; Zhu, Miaojin; Liang, Jiaming; Zhang, Zheyuan; Zhang, Xiaodi; Dong, Dongyang et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

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.