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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited 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

Published Date

  • October 22, 2021

Published In

Volume / Issue

  • 374 / 6566

Start / End Page

  • 472 - 478

PubMed ID

  • 34554826

Pubmed Central ID

  • PMC9302186

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.abh2315

Language

  • eng

Conference Location

  • United States