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TitleSomatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1058, Year 2023
Publish dateFeb 24, 2023
AuthorsHaisheng Yu / Banghui Liu / Yudi Zhang / Xijie Gao / Qian Wang / Haitao Xiang / Xiaofang Peng / Caixia Xie / Yaping Wang / Peiyu Hu / Jingrong Shi / Quan Shi / Pingqian Zheng / Chengqian Feng / Guofang Tang / Xiaopan Liu / Liliangzi Guo / Xiumei Lin / Jiaojiao Li / Chuanyu Liu / Yaling Huang / Naibo Yang / Qiuluan Chen / Zimu Li / Mengzhen Su / Qihong Yan / Rongjuan Pei / Xinwen Chen / Longqi Liu / Fengyu Hu / Dan Liang / Bixia Ke / Changwen Ke / Feng Li / Jun He / Meiniang Wang / Ling Chen / Xiaoli Xiong / Xiaoping Tang /
PubMed AbstractSARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients ...SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.
External linksNat Commun / PubMed:36828833 / PubMed Central
MethodsEM (single particle)
Resolution3.43 - 6.21 Å
Structure data

34649

8hc2

EMDB-34649, PDB-8hc2:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 1 YB9-258 Fab (1 RBD up)
Method: EM (single particle) / Resolution: 6.21 Å

34650

8hc3

EMDB-34650, PDB-8hc3:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 2 YB9-258 Fabs (2 RBD up)
Method: EM (single particle) / Resolution: 4.35 Å

34651

8hc4

EMDB-34651, PDB-8hc4:
SARS-CoV-2 wildtype spike trimer (6P) in complex with 3 YB9-258 Fabs and 3 R1-32 Fabs (3 RBD up)
Method: EM (single particle) / Resolution: 3.54 Å

34652

8hc5

EMDB-34652, PDB-8hc5:
SARS-CoV-2 wildtype S1 in complex with YB9-258 Fab and R1-32 Fab
Method: EM (single particle) / Resolution: 3.43 Å

34653

8hc6

EMDB-34653, PDB-8hc6:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with YB9-258 Fab, focused refinement of Fab region
Method: EM (single particle) / Resolution: 4.69 Å

34654

8hc7

EMDB-34654, PDB-8hc7:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) complex with YB9-258 Fab, focused refinement of RBD-dimer region
Method: EM (single particle) / Resolution: 4.54 Å

34655

8hc8

EMDB-34655, PDB-8hc8:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with YB13-292 Fab, focused refinement of Fab region
Method: EM (single particle) / Resolution: 3.95 Å

34656

8hc9

EMDB-34656, PDB-8hc9:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 3 YB13-292 Fabs (3 RBD down)
Method: EM (single particle) / Resolution: 6.03 Å

34657

8hca

EMDB-34657, PDB-8hca:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 3 YB13-292 Fabs (1 RBD up)
Method: EM (single particle) / Resolution: 4.35 Å

34658

8hcb

EMDB-34658, PDB-8hcb:
SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 3 YB13-292 Fabs (2 RBD up)
Method: EM (single particle) / Resolution: 4.18 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Spike protein / RBD / antibody / Fab / Viral protein / VIRAL PROTEIN-IMMUNE SYSTEM complex

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