Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.
Embargo End Date
ICR Authors
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
CoVIC-DB team1,
Aldon, Y
Ali, H
Aracic, S
Cobb, RR
Federman, RS
Fernandez, JM
Glanville, J
Green, R
Grigoryan, G
Lujan Hernandez, AG
Ho, DD
Huang, K-YA
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
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
CoVIC-DB team1,
Aldon, Y
Ali, H
Aracic, S
Cobb, RR
Federman, RS
Fernandez, JM
Glanville, J
Green, R
Grigoryan, G
Lujan Hernandez, AG
Ho, DD
Huang, K-YA
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
Document Type
Journal Article
Date
2021-10-22
Date Accepted
2021-09-01
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.
Citation
Science (New York, N.Y.), 2021, 374 (6566), pp. 472 - 478
Source Title
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
ISSN
0036-8075
eISSN
1095-9203
Collections
Research Team
Chromosomal Translocations and Intracellular Antibody Therapeutics