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bioRxiv · 10.1101/2025.02.28.640788

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

Yao, H.·Song, Y.·Huang, Q.·Zhu, M.·Liang, J.·Zhang, Z.·Zhang, X.·Dong, D.·Shi, D.·Wu, Z.·Lu, X.·Wu, H.·Chen, Y.·Li, S.
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Abstract

The bivalent nature of IgG enhances its neutralization potency against enveloped viruses; however, on-virion structural details of IgG bivalent binding with antigens remain elusive. Here we used cryo-ET to investigate how two potent IgGs P17 and S309 interact with S-trimers on the SARS-CoV-2 surface. We found that these antibodies exploit the mobility of S-trimers to form diverse bivalent binding patterns. P17 stabilizes S-trimers in a one-RBD-up conformation and gathers S-trimer into linear multimers within minutes, whereas S309 primarily forms circular S-trimer assemblies that extend into lattice-like structures. Additionally, both IgGs can facilitate inter-virion coupling through bivalent binding of opposing S-trimers. These findings provide a structural basis for understanding IgG avidity and offer insights for antibody engineering and vaccine design.

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Yao, H., Song, Y., Huang, Q., Zhu, M., Liang, J., Zhang, Z., Zhang, X., Dong, D., Shi, D., Wu, Z., Lu, X., Wu, H., Chen, Y., Li, S.. 2025-03-02. Cryo-ET of IgG bivalent binding on SARS-CoV-2 provides structural basis for antibody avidity. https://doi.org/10.1101/2025.02.28.640788

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