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

Author

Listed:
  • Rita E. Chen

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Emma S. Winkler

    (Washington University School of Medicine
    Washington University School of Medicine)

  • James Brett Case

    (Washington University School of Medicine)

  • Ishmael D. Aziati

    (Washington University School of Medicine)

  • Traci L. Bricker

    (Washington University School of Medicine)

  • Astha Joshi

    (Washington University School of Medicine)

  • Tamarand L. Darling

    (Washington University School of Medicine)

  • Baoling Ying

    (Washington University School of Medicine)

  • John M. Errico

    (Washington University School of Medicine)

  • Swathi Shrihari

    (Washington University School of Medicine)

  • Laura A. VanBlargan

    (Washington University School of Medicine)

  • Xuping Xie

    (University of Texas Medical Branch)

  • Pavlo Gilchuk

    (Vanderbilt University Medical Center)

  • Seth J. Zost

    (Vanderbilt University Medical Center)

  • Lindsay Droit

    (Washington University School of Medicine)

  • Zhuoming Liu

    (Washington University School of Medicine)

  • Spencer Stumpf

    (Washington University School of Medicine)

  • David Wang

    (Washington University School of Medicine)

  • Scott A. Handley

    (Washington University School of Medicine)

  • W. Blaine Stine

    (AbbVie Bioresearch Center)

  • Pei-Yong Shi

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Meredith E. Davis-Gardner

    (Emory University School of Medicine)

  • Mehul S. Suthar

    (Emory University School of Medicine)

  • Miguel Garcia Knight

    (University of California San Francisco)

  • Raul Andino

    (University of California San Francisco)

  • Charles Y. Chiu

    (University of California San Francisco
    University of California San Francisco)

  • Ali H. Ellebedy

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Daved H. Fremont

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Sean P. J. Whelan

    (Washington University School of Medicine)

  • James E. Crowe

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Microbiology and Immunology, Vanderbilt University Medical Center)

  • Lisa Purcell

    (Vir Biotechnology)

  • Davide Corti

    (a subsidiary of Vir Biotechnology)

  • Adrianus C. M. Boon

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

Abstract

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-21–3, 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.

Suggested Citation

  • Rita E. Chen & Emma S. Winkler & James Brett Case & Ishmael D. Aziati & Traci L. Bricker & Astha Joshi & Tamarand L. Darling & Baoling Ying & John M. Errico & Swathi Shrihari & Laura A. VanBlargan & X, 2021. "In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains," Nature, Nature, vol. 596(7870), pages 103-108, August.
  • Handle: RePEc:nat:nature:v:596:y:2021:i:7870:d:10.1038_s41586-021-03720-y
    DOI: 10.1038/s41586-021-03720-y
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    Cited by:

    1. Shelly J. Robertson & Olivia Bedard & Kristin L. McNally & Carl Shaia & Chad S. Clancy & Matthew Lewis & Rebecca M. Broeckel & Abhilash I. Chiramel & Jeffrey G. Shannon & Gail L. Sturdevant & Rebecca , 2023. "Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Anna R. Mäkelä & Hasan Uğurlu & Liina Hannula & Ravi Kant & Petja Salminen & Riku Fagerlund & Sanna Mäki & Anu Haveri & Tomas Strandin & Lauri Kareinen & Jussi Hepojoki & Suvi Kuivanen & Lev Levanov &, 2023. "Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Elizabeth M. Parzych & Jianqiu Du & Ali R. Ali & Katherine Schultheis & Drew Frase & Trevor R. F. Smith & Jiayan Cui & Neethu Chokkalingam & Nicholas J. Tursi & Viviane M. Andrade & Bryce M. Warner & , 2022. "DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. James Brett Case & Samantha Mackin & John M. Errico & Zhenlu Chong & Emily A. Madden & Bradley Whitener & Barbara Guarino & Michael A. Schmid & Kim Rosenthal & Kuishu Ren & Ha V. Dang & Gyorgy Snell &, 2022. "Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Heli Lu & Menglin Xia & Ziyuan Qin & Siqi Lu & Ruimin Guan & Yuna Yang & Changhong Miao & Taizheng Chen, 2022. "The Built Environment Assessment of Residential Areas in Wuhan during the Coronavirus Disease (COVID-19) Outbreak," IJERPH, MDPI, vol. 19(13), pages 1-20, June.
    7. Daniel N. Streblow & Alec J. Hirsch & Jeffrey J. Stanton & Anne D. Lewis & Lois Colgin & Ann J. Hessell & Craig N. Kreklywich & Jessica L. Smith & William F. Sutton & David Chauvin & Jennifer Woo & Be, 2023. "Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Biao Zhou & Runhong Zhou & Bingjie Tang & Jasper Fuk-Woo Chan & Mengxiao Luo & Qiaoli Peng & Shuofeng Yuan & Hang Liu & Bobo Wing-Yee Mok & Bohao Chen & Pui Wang & Vincent Kwok-Man Poon & Hin Chu & Ch, 2022. "A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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