In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains,Nature

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In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains
Nature ( IF 50.5 ) Pub Date : 2021-06-21 , DOI: 10.1038/s41586-021-03720-y
Rita E Chen _{1,

2} , Emma S Winkler _{1,

2} , James Brett Case ₁ , Ishmael D Aziati ₁ , Traci L Bricker ₁ , Astha Joshi ₁ , Tamarand L Darling ₁ , Baoling Ying ₁ , John M Errico ₂ , Swathi Shrihari ₁ , Laura A VanBlargan ₁ , Xuping Xie ₃ , Pavlo Gilchuk ₄ , Seth J Zost ₄ , Lindsay Droit ₅ , Zhuoming Liu ₅ , Spencer Stumpf ₅ , David Wang ₅ , Scott A Handley ₂ , W Blaine Stine ₆ , Pei-Yong Shi _{3,

7,

8} , Meredith E Davis-Gardner ₉ , Mehul S Suthar ₉ , Miguel Garcia Knight ₁₀ , Raul Andino ₁₀ , Charles Y Chiu _{11,

12} , Ali H Ellebedy _{2,

13,

14} , Daved H Fremont _{2,

5,

15} , Sean P J Whelan ₅ , James E Crowe _{4,

16,

17} , Lisa Purcell ₁₈ , Davide Corti ₁₉ , Adrianus C M Boon _{1,

2,

5} , Michael S Diamond _{1,

2,

5,

13,

14}

Affiliation

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
AbbVie Bioresearch Center, Worcester, MA, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.
Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA.
Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St Louis, MO, USA.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, USA.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Vir Biotechnology, St Louis, MO, USA.
Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-2^1,2,3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many—but not all—of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.

中文翻译：

体内单克隆抗体对 SARS-CoV-2 变异株的功效

迅速出现的 SARS-CoV-2 变种危及基于抗体的对策。尽管细胞培养实验已证明几种抗尖峰中和抗体针对 SARS-CoV-2 变异株的效力丧失^1,2,3，但这些结果的体内重要性仍不确定。在此，我们报告了一组单克隆抗体 (mAb) 的体外和体内活性，这些单克隆抗体与 Vir Biotechnology、艾伯维、阿斯利康、再生元和礼来公司针对 SARS-CoV-2 变异病毒的高级临床开发中的许多抗体相对应。尽管某些单克隆抗体在细胞培养物中针对刺突蛋白残基 E484 发生突变的 B.1.351、B.1.1.28、B.1.617.1 和 B.1.526 病毒表现出降低或消除的中和活性，但单克隆抗体组合的预防剂量较低在 K18-hACE2 转基因小鼠、129S2 免疫活性小鼠和仓鼠中，可防止多种变体的感染，且不会出现耐药性。例外情况是 LY-CoV555 单药治疗以及 LY-CoV555 和 LY-CoV016 联合治疗，两者均失去了所有保护活性，以及艾伯维 2B04 和 47D11 的联合治疗，显示部分活性丧失。感染后施用时，较高剂量的几种单克隆抗体混合物可以在体内保护体内免受带有 B.1.351 刺突基因的病毒的侵害。因此，许多（但不是全部）获得紧急使用授权的抗体产品应保留针对流行的 SARS-CoV-2 变异毒株的实质性功效。

更新日期：2021-06-21

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