Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Elife. 2020 Oct 28;9:e61312. doi: 10.7554/eLife.61312.
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.
先前感染或接种疫苗所产生的中和抗体可能是未来保护个人和人群免受 SARS-CoV-2 侵害的关键。此外，被动给予的抗体是最有前途的治疗和预防 SARS-CoV-2 的药物之一。然而，SARS-CoV-2 逃避中和抗体的程度尚不清楚。我们使用重组嵌合 VSV/SARS-CoV-2 报告病毒表明，在受体结合域（RBD）和 N 端结构域中具有突变的功能性 SARS-CoV-2 S 蛋白变体可轻易被选择出来，这些突变赋予了对单克隆抗体或恢复期血浆的抗性。值得注意的是，目前在循环 SARS-CoV-2 人群中，可抵抗常见中和抗体的 SARS-CoV-2 变体以低频率存在。最后，通过使用针对不同中和表位的抗体组合，可以减轻出现可能限制单克隆抗体治疗效果的抗体耐药性 SARS-CoV-2 变体的问题。
