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A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice

David R. Martinez, Alexandra Schaefer, View ORCID ProfileSophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, Maggie Barr, Kartik Manne, Katayoun Mansouri, Robert J. Edwards, Boyd Yount, Kara Anasti, View ORCID ProfileStephanie A. Montgomery, Shaunna Shen, Tongqing Zhou, Peter D. Kwong, View ORCID ProfileBarney S. Graham, John R. Mascola, David. C. Montefiori, Munir Alam, Gregory D. Sempowski, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Barton F. Haynes, Ralph S. Baric
doi: https://doi.org/10.1101/2021.04.27.441655
David R. Martinez
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Alexandra Schaefer
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Sophie Gobeil
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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  • ORCID record for Sophie Gobeil
Dapeng Li
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Gabriela De la Cruz
3Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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Robert Parks
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Xiaozhi Lu
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Maggie Barr
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Kartik Manne
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Katayoun Mansouri
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Robert J. Edwards
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Boyd Yount
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Kara Anasti
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Stephanie A. Montgomery
4Department of Laboratory Medicine and Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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  • ORCID record for Stephanie A. Montgomery
Shaunna Shen
6Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Tongqing Zhou
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
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Peter D. Kwong
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
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Barney S. Graham
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
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John R. Mascola
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
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David. C. Montefiori
6Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Munir Alam
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Gregory D. Sempowski
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Kevin Wiehe
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Kevin O. Saunders
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
6Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Priyamvada Acharya
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
6Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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  • For correspondence: priyamvada.acharya@duke.edu barton.haynes@duke.edu rbaric@email.unc.edu
Barton F. Haynes
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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  • For correspondence: priyamvada.acharya@duke.edu barton.haynes@duke.edu rbaric@email.unc.edu
Ralph S. Baric
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • For correspondence: priyamvada.acharya@duke.edu barton.haynes@duke.edu rbaric@email.unc.edu
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Abstract

SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

Competing Interest Statement

Duke University has filed provisional patents for which B.F.H, K.O.S., D.L., and G.D.S., are inventors on a provisional U.S. patent for mAb DH1047 and its applications described in this study.

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 4.0 International license.
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Posted April 28, 2021.
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A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice
David R. Martinez, Alexandra Schaefer, Sophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, Maggie Barr, Kartik Manne, Katayoun Mansouri, Robert J. Edwards, Boyd Yount, Kara Anasti, Stephanie A. Montgomery, Shaunna Shen, Tongqing Zhou, Peter D. Kwong, Barney S. Graham, John R. Mascola, David. C. Montefiori, Munir Alam, Gregory D. Sempowski, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Barton F. Haynes, Ralph S. Baric
bioRxiv 2021.04.27.441655; doi: https://doi.org/10.1101/2021.04.27.441655
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A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice
David R. Martinez, Alexandra Schaefer, Sophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, Maggie Barr, Kartik Manne, Katayoun Mansouri, Robert J. Edwards, Boyd Yount, Kara Anasti, Stephanie A. Montgomery, Shaunna Shen, Tongqing Zhou, Peter D. Kwong, Barney S. Graham, John R. Mascola, David. C. Montefiori, Munir Alam, Gregory D. Sempowski, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Barton F. Haynes, Ralph S. Baric
bioRxiv 2021.04.27.441655; doi: https://doi.org/10.1101/2021.04.27.441655

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