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| Title | Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants. |
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| Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 7585, Year 2024 |
| Publish date | Aug 31, 2024 |
Authors | Qihong Yan / Xijie Gao / Banghui Liu / Ruitian Hou / Ping He / Yong Ma / Yudi Zhang / Yanjun Zhang / Zimu Li / Qiuluan Chen / Jingjing Wang / Xiaohan Huang / Huan Liang / Huiran Zheng / Yichen Yao / Xianying Chen / Xuefeng Niu / Jun He / Ling Chen / Jincun Zhao / Xiaoli Xiong / ![]() |
| PubMed Abstract | Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants ...Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity. |
External links | Nat Commun / PubMed:39217172 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.16 - 8.45 Å |
| Structure data | EMDB-60099, PDB-8zhd: EMDB-60100, PDB-8zhe: EMDB-60101, PDB-8zhf: EMDB-60102, PDB-8zhg: EMDB-60103, PDB-8zhh: EMDB-60104, PDB-8zhi: EMDB-60105, PDB-8zhj: EMDB-60106, PDB-8zhk: EMDB-60107, PDB-8zhl: EMDB-60108, PDB-8zhm: EMDB-60109, PDB-8zhn: EMDB-60110, PDB-8zho: EMDB-60111, PDB-8zhp: |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Spike protein / RBD / Antibody / Fab / Viral protein / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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enterobacteria phage t6 (virus)
homo sapiens (human)
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