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bioRxiv · 10.1101/2020.06.08.141267

Structural basis of a public antibody response to SARS-CoV-2

Yuan, M.·Liu, H.·Wu, N. C.·Lee, C.-C. D.·Zhu, X.·Zhao, F.·Huang, D.·Yu, W.·Hua, Y.·Tien, H.·Rogers, T. F.·Landais, E.·Sok, D.·Jardine, J. G.·Burton, D. R.·Wilson, I. A.
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Abstract

Molecular-level understanding of human neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and facilitate drug discovery. We analyzed 294 SARS-CoV-2 antibodies and found that IGHV3-53 is the most frequently used IGHV gene for targeting the receptor binding domain (RBD) of the spike (S) protein. We determined crystal structures of two IGHV3-53 neutralizing antibodies +/- Fab CR3022 ranging from 2.33 to 3.11 [A] resolution. The germline-encoded residues of IGHV3-53 dominate binding to the ACE2 binding site epitope with no overlap with the CR3022 epitope. Moreover, IGHV3-53 is used in combination with a very short CDR H3 and different light chains. Overall, IGHV3-53 represents a versatile public VH in neutralizing SARS-CoV-2 antibodies, where their specific germline features and minimal affinity maturation provide important insights for vaccine design and assessing outcomes.

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Yuan, M., Liu, H., Wu, N. C., Lee, C.-C. D., Zhu, X., Zhao, F., Huang, D., Yu, W., Hua, Y., Tien, H., Rogers, T. F., Landais, E., Sok, D., Jardine, J. G., Burton, D. R., Wilson, I. A.. 2020-06-09. Structural basis of a public antibody response to SARS-CoV-2. https://doi.org/10.1101/2020.06.08.141267

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