Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 01 2023
19 01 2023
Historique:
received:
15
09
2022
accepted:
09
01
2023
entrez:
18
1
2023
pubmed:
19
1
2023
medline:
21
1
2023
Statut:
epublish
Résumé
Waves of SARS-CoV-2 infection have resulted from the emergence of viral variants with neutralizing antibody resistance mutations. Simultaneously, repeated antigen exposure has generated affinity matured B cells, producing broadly neutralizing receptor binding domain (RBD)-specific antibodies with activity against emergent variants. To determine how SARS-CoV-2 might escape these antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection by 40 broadly neutralizing antibodies. We identify numerous examples of epistasis, whereby in vitro selected and naturally occurring substitutions in RBD epitopes that do not confer antibody resistance in the Wuhan-Hu-1 spike, do so in BA.1 or BA.2 spikes. As few as 2 or 3 of these substitutions in the BA.5 spike, confer resistance to nearly all of the 40 broadly neutralizing antibodies, and substantial resistance to plasma from most individuals. Thus, epistasis facilitates the acquisition of resistance to antibodies that remained effective against early omicron variants.
Identifiants
pubmed: 36653360
doi: 10.1038/s41467-023-35927-0
pii: 10.1038/s41467-023-35927-0
pmc: PMC9849103
doi:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
Spike Glycoprotein, Coronavirus
0
Antibodies, Viral
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
302Subventions
Organisme : NIAID NIH HHS
ID : U19 AI111825
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138938
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI078788
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI064003
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI165075
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
Références
Nature. 2020 Aug;584(7821):437-442
pubmed: 32555388
Elife. 2020 Oct 28;9:
pubmed: 33112236
Immunity. 2021 Aug 10;54(8):1853-1868.e7
pubmed: 34331873
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32692348
Nature. 2021 Dec;600(7889):517-522
pubmed: 34619745
Science. 2004 Jan 16;303(5656):327-32
pubmed: 14726583
Viruses. 2022 Jun 18;14(6):
pubmed: 35746806
Cell Rep. 2021 Sep 28;36(13):109760
pubmed: 34534459
Nature. 2021 Apr;592(7855):616-622
pubmed: 33567448
Nature. 2021 Mar;591(7851):639-644
pubmed: 33461210
Cell. 2020 Nov 25;183(5):1298-1311.e11
pubmed: 33125897
J Exp Med. 2022 Dec 5;219(12):
pubmed: 36149398
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
Open Forum Infect Dis. 2022 May 07;9(7):ofac227
pubmed: 35818364
Nature. 2021 Jul;595(7867):426-431
pubmed: 34126625
Sci Immunol. 2022 Jul 29;7(73):eabq3511
pubmed: 35549299
Nature. 2022 Feb;602(7898):664-670
pubmed: 35016195
Nat Med. 2021 Apr;27(4):622-625
pubmed: 33654292
Nature. 2022 Feb;602(7898):671-675
pubmed: 35016199
Nature. 2022 Feb;602(7898):654-656
pubmed: 35016196
Cell Host Microbe. 2021 Mar 10;29(3):463-476.e6
pubmed: 33592168
Nature. 2022 Aug;608(7923):593-602
pubmed: 35714668
J Gen Virol. 2019 May;100(5):773-777
pubmed: 31017567
Nature. 2022 Apr;604(7906):553-556
pubmed: 35240676
Nat Med. 2022 Sep;28(9):1785-1790
pubmed: 35760080
Nature. 2021 Aug;596(7870):109-113
pubmed: 34182569
Immunity. 2022 Aug 9;55(8):1501-1514.e3
pubmed: 35777362
N Engl J Med. 2022 Feb 10;386(6):599-601
pubmed: 35030645
Nature. 2021 Dec;600(7889):512-516
pubmed: 34544114
Nature. 2022 Feb;602(7898):657-663
pubmed: 35016194
Nat Med. 2022 Dec 6;:
pubmed: 36473500
Nature. 2022 Jul;607(7917):128-134
pubmed: 35447027