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Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

View ORCID ProfilePengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, View ORCID ProfileBarney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, View ORCID ProfileChristos A. Kyratsous, Lawrence Shapiro, View ORCID ProfileZizhang Sheng, Yaoxing Huang, David D. Ho
doi: https://doi.org/10.1101/2021.01.25.428137
Pengfei Wang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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  • ORCID record for Pengfei Wang
Manoj S. Nair
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Lihong Liu
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Sho Iketani
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA
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Yang Luo
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Yicheng Guo
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Maple Wang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Jian Yu
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Baoshan Zhang
3Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
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Peter D. Kwong
3Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
4Department of Biochemistry, Columbia University, New York, NY, USA
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Barney S. Graham
3Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
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  • ORCID record for Barney S. Graham
John R. Mascola
3Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA
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Jennifer Y. Chang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
5Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Michael T. Yin
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
5Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Magdalena Sobieszczyk
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
5Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Christos A. Kyratsous
6Regeneron Pharmaceuticals, Inc., Tarrytown, NY. USA
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  • ORCID record for Christos A. Kyratsous
Lawrence Shapiro
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
4Department of Biochemistry, Columbia University, New York, NY, USA
7Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
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Zizhang Sheng
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Yaoxing Huang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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  • For correspondence: yh3253@cumc.columbia.edu dh2994@cumc.columbia.edu
David D. Ho
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA
5Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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  • For correspondence: yh3253@cumc.columbia.edu dh2994@cumc.columbia.edu
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Abstract

The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1–3, with more in the pipeline4–7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

Competing Interest Statement

P.W., L.L, J.Y., M.N., Y.H., and D.D.H. are inventors on a provisional patent application on mAbs to SARS-CoV-2. D.D.H. is a member of the scientific advisory board of Brii Biosciences, which also has provided a grant to Columbia University to support this and other studies on SARS-CoV-2.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 12, 2021.
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Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho
bioRxiv 2021.01.25.428137; doi: https://doi.org/10.1101/2021.01.25.428137
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Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho
bioRxiv 2021.01.25.428137; doi: https://doi.org/10.1101/2021.01.25.428137

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