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Journal article

Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

Abstract:
The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called 'FLip' mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-024-47393-3

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Centre for Human Genetics
Role:
Author
ORCID:
0009-0008-8169-4572
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Centre for Human Genetics
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:
Structural Biology
Role:
Author
ORCID:
0000-0002-7188-5243
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Centre for Human Genetics
Oxford college:
Keble College
Role:
Author
ORCID:
0000-0002-4502-2209


More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/N00065X/1
More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
203141/Z/16/Z
090532/Z/09/Z
More from this funder
Funder identifier:
https://ror.org/0187kwz08
Grant:
NIHR300791


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
15
Issue:
1
Article number:
3284
Place of publication:
England
Publication date:
2024-04-16
Acceptance date:
2024-03-29
DOI:
EISSN:
2041-1723
Pmid:
38627386


Language:
English
Pubs id:
1991231
Local pid:
pubs:1991231
Deposit date:
2024-12-18

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