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The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
Dapeng Li, Robert J Edwards, Kartik Manne, David R. Martinez, Alexandra Schäfer, S. Munir Alam, Kevin Wiehe, Xiaozhi Lu, Robert Parks, Laura L. Sutherland, Thomas H. Oguin III, Charlene McDanal, Lautaro G. Perez, Katayoun Mansouri, View ORCID ProfileSophie M. C. Gobeil, Katarzyna Janowska, Victoria Stalls, Megan Kopp, Fangping Cai, Esther Lee, Andrew Foulger, Giovanna E. Hernandez, Aja Sanzone, Kedamawit Tilahun, Chuancang Jiang, Longping V. Tse, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Kenneth Cronin, Victoria Gee-Lai, Margaret Deyton, Maggie Barr, Tarra Von Holle, Andrew N. Macintyre, Erica Stover, View ORCID ProfileJared Feldman, View ORCID ProfileBlake M. Hauser, Timothy M. Caradonna, Trevor D. Scobey, Wes Rountree, Yunfei Wang, M. Anthony Moody, Derek W. Cain, C. Todd DeMarco, ThomasN. Denny, Christopher W. Woods, Elizabeth W. Petzold, View ORCID ProfileAaron G. Schmidt, I-Ting Teng, Tongqing Zhou, Peter D. Kwong, John R. Mascola, View ORCID ProfileBarney S. Graham, Ian N. Moore, Robert Seder, Hanne Andersen, Mark G. Lewis, David C. Montefiori, Gregory D. Sempowski, Ralph S. Baric, Priyamvada Acharya, Barton F. Haynes, View ORCID ProfileKevin O. Saunders
doi: https://doi.org/10.1101/2020.12.31.424729
Dapeng Li
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Robert J Edwards
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Kartik Manne
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
David R. Martinez
3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Alexandra Schäfer
3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
S. Munir Alam
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Kevin Wiehe
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Xiaozhi Lu
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Robert Parks
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Laura L. Sutherland
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Thomas H. Oguin III
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Charlene McDanal
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Lautaro G. Perez
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Katayoun Mansouri
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Sophie M. C. Gobeil
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Katarzyna Janowska
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Victoria Stalls
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Megan Kopp
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Fangping Cai
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Esther Lee
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Andrew Foulger
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Giovanna E. Hernandez
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Aja Sanzone
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Kedamawit Tilahun
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Chuancang Jiang
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Longping V. Tse
3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Kevin W. Bock
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Mahnaz Minai
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Bianca M. Nagata
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kenneth Cronin
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Victoria Gee-Lai
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Margaret Deyton
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Maggie Barr
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Tarra Von Holle
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Andrew N. Macintyre
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Erica Stover
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Jared Feldman
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Blake M. Hauser
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Timothy M. Caradonna
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Trevor D. Scobey
3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Wes Rountree
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Yunfei Wang
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
M. Anthony Moody
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
7Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA
Derek W. Cain
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
C. Todd DeMarco
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
ThomasN. Denny
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Christopher W. Woods
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
8Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC 27710, USA
Elizabeth W. Petzold
8Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC 27710, USA
Aaron G. Schmidt
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
9Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
I-Ting Teng
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
Tongqing Zhou
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
Peter D. Kwong
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
11Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
John R. Mascola
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
Barney S. Graham
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
Ian N. Moore
4Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Robert Seder
10Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA
Hanne Andersen
12BIOQUAL, Rockville, MD 20850, USA
Mark G. Lewis
12BIOQUAL, Rockville, MD 20850, USA
David C. Montefiori
5Department of Surgery, Duke University, Durham, NC 27710, USA
Gregory D. Sempowski
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
Ralph S. Baric
3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Priyamvada Acharya
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
5Department of Surgery, Duke University, Durham, NC 27710, USA
Barton F. Haynes
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
13Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA
Kevin O. Saunders
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
5Department of Surgery, Duke University, Durham, NC 27710, USA
13Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA
14Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
Summary
SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.
Competing Interest Statement
The authors have declared no competing interest.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted February 18, 2021.
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
Dapeng Li, Robert J Edwards, Kartik Manne, David R. Martinez, Alexandra Schäfer, S. Munir Alam, Kevin Wiehe, Xiaozhi Lu, Robert Parks, Laura L. Sutherland, Thomas H. Oguin III, Charlene McDanal, Lautaro G. Perez, Katayoun Mansouri, Sophie M. C. Gobeil, Katarzyna Janowska, Victoria Stalls, Megan Kopp, Fangping Cai, Esther Lee, Andrew Foulger, Giovanna E. Hernandez, Aja Sanzone, Kedamawit Tilahun, Chuancang Jiang, Longping V. Tse, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Kenneth Cronin, Victoria Gee-Lai, Margaret Deyton, Maggie Barr, Tarra Von Holle, Andrew N. Macintyre, Erica Stover, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Trevor D. Scobey, Wes Rountree, Yunfei Wang, M. Anthony Moody, Derek W. Cain, C. Todd DeMarco, ThomasN. Denny, Christopher W. Woods, Elizabeth W. Petzold, Aaron G. Schmidt, I-Ting Teng, Tongqing Zhou, Peter D. Kwong, John R. Mascola, Barney S. Graham, Ian N. Moore, Robert Seder, Hanne Andersen, Mark G. Lewis, David C. Montefiori, Gregory D. Sempowski, Ralph S. Baric, Priyamvada Acharya, Barton F. Haynes, Kevin O. Saunders
bioRxiv 2020.12.31.424729; doi: https://doi.org/10.1101/2020.12.31.424729
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
Dapeng Li, Robert J Edwards, Kartik Manne, David R. Martinez, Alexandra Schäfer, S. Munir Alam, Kevin Wiehe, Xiaozhi Lu, Robert Parks, Laura L. Sutherland, Thomas H. Oguin III, Charlene McDanal, Lautaro G. Perez, Katayoun Mansouri, Sophie M. C. Gobeil, Katarzyna Janowska, Victoria Stalls, Megan Kopp, Fangping Cai, Esther Lee, Andrew Foulger, Giovanna E. Hernandez, Aja Sanzone, Kedamawit Tilahun, Chuancang Jiang, Longping V. Tse, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Kenneth Cronin, Victoria Gee-Lai, Margaret Deyton, Maggie Barr, Tarra Von Holle, Andrew N. Macintyre, Erica Stover, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Trevor D. Scobey, Wes Rountree, Yunfei Wang, M. Anthony Moody, Derek W. Cain, C. Todd DeMarco, ThomasN. Denny, Christopher W. Woods, Elizabeth W. Petzold, Aaron G. Schmidt, I-Ting Teng, Tongqing Zhou, Peter D. Kwong, John R. Mascola, Barney S. Graham, Ian N. Moore, Robert Seder, Hanne Andersen, Mark G. Lewis, David C. Montefiori, Gregory D. Sempowski, Ralph S. Baric, Priyamvada Acharya, Barton F. Haynes, Kevin O. Saunders
bioRxiv 2020.12.31.424729; doi: https://doi.org/10.1101/2020.12.31.424729
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