Potent cross-reactive antibodies following Omicron breakthrough in vaccinees,Cell

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Potent cross-reactive antibodies following Omicron breakthrough in vaccinees
Cell ( IF 64.5 ) Pub Date : 2022-05-20 , DOI: 10.1016/j.cell.2022.05.014
Rungtiwa Nutalai ₁ , Daming Zhou ₂ , Aekkachai Tuekprakhon ₁ , Helen M Ginn ₃ , Piyada Supasa ₁ , Chang Liu ₄ , Jiandong Huo ₅ , Alexander J Mentzer ₆ , Helen M E Duyvesteyn ₅ , Aiste Dijokaite-Guraliuc ₁ , Donal Skelly ₇ , Thomas G Ritter ₈ , Ali Amini ₉ , Sagida Bibi ₁₀ , Sandra Adele ₈ , Sile Ann Johnson ₈ , Bede Constantinides ₁₁ , Hermione Webster ₁₁ , Nigel Temperton ₁₂ , Paul Klenerman ₁₃ , Eleanor Barnes ₁₃ , Susanna J Dunachie ₁₄ , Derrick Crook ₁₁ , Andrew J Pollard ₁₅ , Teresa Lambe ₁₆ , Philip Goulder ₁₇ , , Neil G Paterson ₃ , Mark A Williams ₃ , David R Hall ₃ , Juthathip Mongkolsapaya ₄ , Elizabeth E Fry ₅ , Wanwisa Dejnirattisai ₁ , Jingshan Ren ₅ , David I Stuart ₁₈ , Gavin R Screaton ₄

Affiliation

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; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, 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; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), 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; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Clinical Neurosciences, 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, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich, Chatham Maritime, Kent ME4 4TB, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Centre For Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.

中文翻译：

Omicron 在疫苗接种者中取得突破后产生有效的交叉反应抗体

SARS-CoV-2 的高传染性 Omicron 变种目前在全球占据主导地位。在这里，我们比较了 Omicron BA.1、BA.1.1 和 BA.2 的中和作用。BA.2 RBD 的 ACE2 亲和力略高于 BA.1，并且疫苗血清的中和作用略有降低，可能与其传播性增加有关。mAb（包括治疗药物）亚谱系之间的中和差异主要源于 ACE2 结合位点边界残基的变化；然而，更远的突变 S371F (BA.2) 和 R346K (BA.1.1) 显着降低了治疗性抗体 Vir-S309 的中和作用。对从突破性 Omicron-BA.1 感染后接种疫苗的志愿者中分离出的 27 种强效 RBD 结合 mAb 进行的深入结构和功能分析表明，它们集中在 RBD 内的两个主要簇中，其中强效右肩抗体显示出患病率增加。选择和体细胞成熟优化了突变较少的表位中的抗体效力，并恢复了高度突变的表位中的抗体效力。所有 27 种单克隆抗体均能有效中和早期大流行毒株，并且许多单克隆抗体对相关变体表现出广泛的反应性。

更新日期：2022-05-20

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