Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study
Kathryn M. Hastie, Haoyang Li, Daniel Bedinger, Sharon L. Schendel, S. Moses Dennison, Kan Li, Vamseedhar Rayaprolu, Xiaoying Yu, Colin Mann, Michelle Zandonatti, Ruben Diaz Avalos, Dawid Zyla, Tierra K. Buck, Sean Hui, Kelly Shaffer, Chitra Hariharan, Jieyun Yin, Eduardo Olmedillas, Adrian Enriquez, Diptiben Parekh, Milite Abraha, Elizabeth Feeney, Gillian Q. Horn, CoVIC-DB team, Yoann Aldon, Hanif Ali, Sanja Aracic, Ronald R. Cobb, Ross S. Federman, Joseph M. Fernandez, Jacob Glanville, Robin Green, Gevorg Grigoryan, Ana González Hernández, David D. Ho, Kuan-Ying A. Huang, John Ingraham, Weidong Jiang, Paul Kellam, Cheolmin Kim, Minsoo Kim, Hyeong Mi Kim, Chao Kong, Shelly J. Krebs, Fei Lan, Guojun Lang, Soo-Young Lee, Cheuk Lun Leung, Junli Liu, Yanan Lu, Anna J. MacCamy, Andrew T. McGuire, Anne Palser, Terence H. Rabbitts, Zahra Rikhtegaran Tehrani, Mohammad M. Sajadi, Rogier W. Sanders, Aaron K. Sato, Liang Schweizer, Ji-Min Seo, Bingqing Shen, Jonne L. Snitselaar, Leonidas Stamatatos, Yongcong Tan, Milan Tomić, Marit J. van Gils, Sawsan Youssef, Jian Yu, Tom Z. Yuan, Q. Zhang, Bjoern Peters, Georgia D. Tomaras, Timothy Germann, Erica Ollmann Saphire
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.