Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
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DOI：
10.1038/s41586-021-03398-2
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发表时间：
2021-03-08
期刊：
影响因子：
64.8
通讯作者：
Ho, David D.
中科院分区：
文献类型：
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作者：
Wang, Pengfei;Nair, Manoj S.;Ho, David D.
新冠肺炎疫情在全球范围内产生了广泛影响，其病原体SARS-CoV-2仍在继续传播。需要制定有效的干预措施来结束这场大流行。使用单抗的单一疗法和联合疗法已获得紧急使用授权(1-3)，更多的治疗方法正在开发中(4-7)。此外，多种疫苗结构已经显示出希望(8)，其中两种对新冠肺炎具有大约95%的保护效力(9，10)。然而，这些干预措施是针对2019年出现的最初的SARS-CoV-2病毒。最近在南非的UK11和B.1.351中检测到SARS-CoV-2变异体B.1.1.7令人担忧(12)，因为据称它们易于传播和Spike蛋白的广泛突变。在这里，我们发现B.1.1.7不能被大多数抗Spike蛋白N-末端结构域的单抗中和，而对少数抗受体结合域的单抗具有相对抵抗力。它对新冠肺炎康复患者的血浆或接种了SARS-CoV-2疫苗的患者的血清并不具有更强的抵抗力。B.1.351变异体不仅不能被大多数抗N-末端结构域的单抗中和，而且也不能被多个单抗中和受体结合域的受体结合基序，这主要是由于突变导致了E484K替换。此外，与野生型SARS-CoV-2相比，B.1.351对恢复期血浆(9.4倍)和来自接种过疫苗的个人血清(10.3-12.4倍)的中和抵抗力明显更强。B.1.351和Spike蛋白突变相似的紧急变异体(13，14)对单抗治疗提出了新的挑战，并威胁到当前疫苗的保护效果。
The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization(1-3), and more treatments are under development(4-7). Furthermore, multiple vaccine constructs have shown promise(8), including two that have an approximately 95% protective efficacy against COVID-19(9,10). However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa(12) is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants(13,14) with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.