The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants,Cell Host & Microbe

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The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2021-11-27 , DOI: 10.1016/j.chom.2021.11.013
Chang Liu ₁ , Daming Zhou ₂ , Rungtiwa Nutalai ₃ , Helen M E Duyvesteyn ₄ , Aekkachai Tuekprakhon ₃ , Helen M Ginn ₅ , Wanwisa Dejnirattisai ₃ , Piyada Supasa ₃ , Alexander J Mentzer ₆ , Beibei Wang ₃ , James Brett Case ₄ , Yuguang Zhao ₄ , Donal T Skelly ₇ , Rita E Chen ₈ , Sile Ann Johnson ₉ , Thomas G Ritter ₁₀ , Chris Mason ₁₀ , Tariq Malik ₁₁ , Nigel Temperton ₁₂ , Neil G Paterson ₅ , Mark A Williams ₅ , David R Hall ₅ , Daniel K Clare ₅ , Andrew Howe ₅ , Philip J R Goulder ₁₃ , Elizabeth E Fry ₄ , Michael S Diamond ₁₄ , Juthathip Mongkolsapaya ₁₅ , Jingshan Ren ₄ , David I Stuart ₁₆ , Gavin R Screaton ₁

Affiliation

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.
Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK.
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.
Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
National Infection Service, Public Health England (PHE), Porton Down, Salisbury, UK.
Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich, Chatham Maritime, Kent ME4 4TB, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK; Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Dean Office for Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK; Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, UK.

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

中文翻译：

对 SARS-CoV-2 Beta 的抗体反应强调了与其他变体的抗原距离

SARS-CoV-2 的 Alpha-B.1.1.7、Beta-B.1.351、Gamma-P.1 和 Delta-B.1.617.2 变体在刺突蛋白 (S) 中表达多种突变。这些可能会改变 S 的抗原结构，导致逃避自然或疫苗诱导的免疫。Beta 特别难以使用早期大流行 SARS-CoV-2 毒株诱导的血清来中和，并且与 Delta 的抗原分离程度最高。为了理解这一点，我们从 Beta 感染个体中生成了 674 种 mAb，并对 27 种最有效的 mAb 进行了详细的结构功能分析：一种结合刺突 N 末端结构域 (NTD)，其余结合受体结合结构域 (RBD) 。其中两种 RBD 结合 mAb 可识别 SARS-CoV-1 和 -2 之间保守的中和表位，而 18 个目标为 Beta 中的突变残基：K417N、E484K 和 N501Y。N501Y 有一个主要反应，包括公共 IgVH4-39 序列，E484K 和 K417N 也是目标。对这些关键残留物的认识强调了为什么来自 Beta 病例的血清不能很好地中和早期大流行病毒和 Delta 病毒。

更新日期：2022-01-12

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