Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
Cell. 2021 Apr 15;184(8):2201-2211.e7. doi: 10.1016/j.cell.2021.02.033. Epub 2021 Feb 18.
SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.
SARS-CoV-2 在一年多的时间里导致了超过 200 万人死亡。疫苗正在大规模接种,旨在针对病毒刺突产生反应。大流行的规模和易错的病毒复制导致了突变病毒的出现,并可能逃避抗体反应。目前在英国占主导地位的变异病毒 B.1.1.7 具有更高的传播性,其刺突中有 9 个氨基酸发生了变化,包括 ACE2 相互作用表面的 N501Y。我们研究了 B.1.1.7 逃避由自然 SARS-CoV-2 感染或疫苗接种引起的抗体反应的能力。我们通过对大量经过充分表征的单克隆抗体进行结构/功能分析来映射 N501Y 的影响。与亲本病毒相比,B.1.1.7 更难被中和,通过与残基 501 的轻链接触,破坏了主要公共抗体类别的一些成员对中和的作用。然而,并未观察到广泛逃避单克隆抗体或由自然感染或疫苗接种产生的抗体反应。