Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

作者：Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Júlio CC Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry L. Luchsinger, Christopher D. Hillyer, Marina F. Caskey, Davide F. Robbiani, Charles M. Rice, Michel C. Nussenzweig, Théodora Hatziioannou, Paul D. Bieniasz · 发表于：eLife · 年份：2020 · DOI：10.7554/elife.61312 · 被引用次数：1468 · 研究领域：SARS-CoV-2 and COVID-19 Research、Monoclonal and Polyclonal Antibodies Research、Viral gastroenteritis research and epidemiology

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.