Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.
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DOI：
10.1101/2020.07.21.214759
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发表时间：
2020-10-28
期刊：
影响因子：
7.7
通讯作者：
Bieniasz, Paul D
中科院分区：
文献类型：
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作者：
Weisblum, Yiska;Schmidt, Fabian;Bieniasz, Paul D
由先前感染或疫苗接种引起的中和抗体可能是未来保护个人和群体免受SARS-CoV-2感染的关键。此外，被动施用的抗体是最有前途的治疗性和预防性抗SARS-CoV-2剂之一。然而，SARS-CoV-2将在多大程度上适应逃避中和抗体尚不清楚。使用重组嵌合VSV/SARS-CoV-2报告病毒，我们表明，功能性SARS-CoV-2 S蛋白变异体与突变的受体结合结构域（RBD）和N-末端结构域，赋予单克隆抗体或恢复期血浆的抗性，可以很容易地选择。值得注意的是，SARS-CoV-2 S变异体抵抗通常引发的中和抗体，目前在循环SARS-CoV-2人群中的频率较低。最后，抗体耐药性SARS-CoV-2变体的出现可能会限制单克隆抗体的治疗有效性，可以通过使用针对不同中和表位的抗体组合来缓解。先前感染或疫苗接种引起的中和抗体可能是未来保护个人和群体免受SARS-CoV-2侵害的关键。此外，被动施用的抗体是最有前途的治疗性和预防性抗SARS-CoV-2剂之一。然而，SARS-CoV-2将在多大程度上适应逃避中和抗体尚不清楚。使用重组嵌合VSV/SARS-CoV-2报告病毒，我们表明，功能性SARS-CoV-2 S蛋白变异体的受体结合结构域（RBD）和N-末端结构域的突变，赋予单克隆抗体或恢复期血浆的抗性，可以很容易地选择。值得注意的是，SARS-CoV-2 S变异体抵抗通常引发的中和抗体，目前在循环SARS-CoV-2人群中的频率较低。最后，抗体抗性SARS-CoV-2变体的出现可能限制单克隆抗体的治疗有效性，可以通过使用靶向不同中和表位的抗体组合来缓解。
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.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.