7E86

Crystal structure of the SARS-CoV-2 S RBD in complex with BD-508 Fab

7E86 の概要

• エントリーDOI: 10.2210/pdb7e86/pdb
• 分子名称: Spike protein S1, BD-508 Fab Heavy Chain, BD-508 Fab Light Chain (3 entities in total)
• 機能のキーワード: sars-cov-2, antibody, viral protein, immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 68797.75

構造登録者

Gao, C.,Xiao, J. (登録日: 2021-03-01, 公開日: 2021-06-09, 最終更新日: 2024-10-30)

主引用文献

Cao, Y.,Yisimayi, A.,Bai, Y.,Huang, W.,Li, X.,Zhang, Z.,Yuan, T.,An, R.,Wang, J.,Xiao, T.,Du, S.,Ma, W.,Song, L.,Li, Y.,Li, X.,Song, W.,Wu, J.,Liu, S.,Li, X.,Zhang, Y.,Su, B.,Guo, X.,Wei, Y.,Gao, C.,Zhang, N.,Zhang, Y.,Dou, Y.,Xu, X.,Shi, R.,Lu, B.,Jin, R.,Ma, Y.,Qin, C.,Wang, Y.,Feng, Y.,Xiao, J.,Xie, X.S.
Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.
Cell Res., 31:732-741, 2021

PubMed Abstract: SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242-244 deletion (242-244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242-244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

PubMed: 34021265
DOI: 10.1038/s41422-021-00514-9

実験手法

X-RAY DIFFRACTION (2.9 Å)