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A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Abstract:
BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.xcrm.2024.101553

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM (CAMS)
Role:
Author
ORCID:
0000-0003-4250-0989
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM (CAMS)
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Centre for Human Genetics
Role:
Author
ORCID:
0000-0002-4850-9709
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM (CAMS)
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
ORCID:
0000-0002-4641-5442


More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/W02067X/1
MR/X009297/1
More from this funder
Funder identifier:
https://ror.org/01cwqze88
Grant:
U19 I082360
More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
203141/A/16/Z
101122/Z/13/Z
226120/Z/22/Z
WT222426/Z/21/Z
207537/Z/17/Z
090532/Z/09/Z
203141/Z/16/Z
More from this funder
Funder identifier:
https://ror.org/042pgcv68
Grant:
2018-I2M-2-002


Publisher:
Cell Press
Journal:
Cell Reports Medicine More from this journal
Volume:
5
Issue:
5
Pages:
101553-101553
Article number:
101553
Place of publication:
United States
Publication date:
2024-05-08
Acceptance date:
2024-04-11
DOI:
EISSN:
2666-3791
ISSN:
2666-3791
Pmid:
38723626


Language:
English
Keywords:
Pubs id:
1995567
UUID:
uuid_d9337d59-ce38-4992-9c2b-f6a30293b89a
Local pid:
pubs:1995567
Source identifiers:
W4396750360
Deposit date:
2025-02-11
ARK identifier:

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