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Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Authors :
Hastie KM
Li H
Bedinger D
Schendel SL
Dennison SM
Li K
Rayaprolu V
Yu X
Mann C
Zandonatti M
Diaz Avalos R
Zyla D
Buck T
Hui S
Shaffer K
Hariharan C
Yin J
Olmedillas E
Enriquez A
Parekh D
Abraha M
Feeney E
Horn GQ
Aldon Y
Ali H
Aracic S
Cobb RR
Federman RS
Fernandez JM
Glanville J
Green R
Grigoryan G
Lujan Hernandez AG
Ho DD
Huang KA
Ingraham J
Jiang W
Kellam P
Kim C
Kim M
Kim HM
Kong C
Krebs SJ
Lan F
Lang G
Lee S
Leung CL
Liu J
Lu Y
MacCamy A
McGuire AT
Palser AL
Rabbitts TH
Rikhtegaran Tehrani Z
Sajadi MM
Sanders RW
Sato AK
Schweizer L
Seo J
Shen B
Snitselaar JL
Stamatatos L
Tan Y
Tomic MT
van Gils MJ
Youssef S
Yu J
Yuan TZ
Zhang Q
Peters B
Tomaras GD
Germann T
Saphire EO
Source :
Science (New York, N.Y.) [Science] 2021 Oct 22; Vol. 374 (6566), pp. 472-478. Date of Electronic Publication: 2021 Sep 23.
Publication Year :
2021

Abstract

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.

Details

Language :
English
ISSN :
1095-9203
Volume :
374
Issue :
6566
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
34554826
Full Text :
https://doi.org/10.1126/science.abh2315