美国斯克里普斯研究所Ian A. Wilson小组揭示SARS-CoV-2共有抗体应答的结构基础。该项研究成果于2020年7月13日在线发表在《科学》杂志上。

Title: Structural basis of a shared antibody response to SARS-CoV-2

Author: Meng Yuan, Hejun Liu, Nicholas C. Wu, Chang-Chun D. Lee, Xueyong Zhu, Fangzhu Zhao, Deli Huang, Wenli Yu, Yuanzi Hua, Henry Tien, Thomas F. Rogers, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton, Ian A. Wilson

Issue&Volume: 2020/07/13

Abstract: AbstractMolecular understanding of neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and drug discovery. We analyzed 294 anti-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 protein. Co-crystal structures of two IGHV3-53 neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33 to 3.20 resolution revealed that the germline-encoded residues dominate recognition of the ACE2 binding site. This binding mode limits the IGHV3-53 antibodies to short CDR H3 loops, but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate design of antigens that elicit this type of neutralizing response.

DOI: 10.1126/science.abd2321

Source: https://science.sciencemag.org/content/early/2020/07/10/science.abd2321