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Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge
Open accessAbstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.
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“previous reports have shown that human neutralizing antibodies protected mice challenged with SARS-CoV (12–14) and Middle East respiratory syndrome (MERS)-CoV (15)”
From An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [13]
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Cites
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
Bats Are Natural Reservoirs of SARS-Like Coronaviruses
Li, W., Shi, Z., Yu, M., Ren, W., Smith, C. S., Epstein, J. H., Wang, H., Crameri, G. S., Hú, Z., Zhang, H., et al. (2005) · Science · doi:10.1126/science.1118391 · Cited by 2,571
Guan, Y., Zheng, B., He, Y., Liu, X. L., Zhuang, Z. X., Cheung, C. L., Luo, S., Li, P. H., Zhang, L., Guan, Y., et al. (2003) · Science · doi:10.1126/science.1087139 · Cited by 2,404
Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor
Li, F., Li, W., Farzan, M., & Harrison, S. C. (2005) · Science · doi:10.1126/science.1116480 · Cited by 2,035
Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome
Kuiken, T., Fouchier, R. A. M., Schutten, M., Rimmelzwaan, G. F., van Amerongen, G., van Riel, D. A. J., Laman, J. D., de Jong, T., van Doornum, G., Lim, W. W. L., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13967-0 · Cited by 1,015
Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2
Li, W., Zhang, C., Sui, J., Kuhn, J. H., Moore, M. J., Luo, S., Wong, S.-K., Huang, I., Xu, K., Vasilieva, N. Y., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600640 · Cited by 993
Immunosenescence: emerging challenges for an ageing population
Aw, D., Silva, A. B., & Palmer, D. B. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02555.x · Cited by 880
Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China
The Chinese SARS Molecular Epidemiology Consortium (2004) · Science · doi:10.1126/science.1092002 · Cited by 765
Traggiai, E., Becker, S., Subbarao, K., Kolesnikova, L., Uematsu, Y., Gismondo, M. R., Murphy, B. R., Rappuoli, R., & Lanzavecchia, A. (2004) · Nature Medicine · doi:10.1038/nm1080 · Cited by 697
Self-citationAn interferon‐γ‐related cytokine storm in SARS patients
Huang, K., Su, I., Theron, M., Wu, Y., Lai, S., Liu, C., & Lei, H. (2005) · Journal of Medical Virology · doi:10.1002/jmv.20255 · Cited by 679
Chan‐Yeung, M., & Xu, R. (2003) · Respirology · doi:10.1046/j.1440-1843.2003.00518.x · Cited by 639
ter Meulen, J., van den Brink, E. N., Poon, L. L. M., Marissen, W. E., Leung, C. S.-W., Cox, F., Cheung, C. Y., Bakker, A. Q., Bogaards, J. A., van Deventer, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030237 · Cited by 599
Yang, Z., Huang, Y. M., Lakshmanan, G., Leung, K., Kong, W., Schwartz, O., Subbarao, K., & Nabel, G. J. (2004) · Journal of Virology · doi:10.1128/jvi.78.11.5642-5650.2004 · Cited by 495
A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice
Roberts, A., Deming, D., Paddock, C. D., Cheng, A., Yount, B. L., Vogel, L., Herman, B. D., Sheahan, T., Heise, M. T., Genrich, G. L., et al. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030005 · Cited by 447
Self-citationBidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line
Dickinson, B. L., Badizadegan, K., Wu, Z., Ahouse, J. C., Zhu, X., Simister, N. E., Blumberg, R. S., & Lencer, W. I. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6968 · Cited by 433
He, Y., Zhou, Y., Liu, S., Kou, Z., Li, W., Farzan, M., & Jiang, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.106 · Cited by 403
Subbarao, K., McAuliffe, J. M., Vogel, L., Fahle, G. A., Fischer, S. H., Tatti, K. M., Packard, M. M., Shieh, W., Zaki, S. R., & Murphy, B. R. (2004) · Journal of Virology · doi:10.1128/jvi.78.7.3572-3577.2004 · Cited by 397
Kan, B., Wang, M., Jing, H., Xu, H., Jiang, X., Yan, M., Liang, W., Zheng, H., Wan, K., Liu, Q., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.18.11892-11900.2005 · Cited by 346
Moore, J. P., & Sodroski, J. (1996) · Journal of Virology · doi:10.1128/jvi.70.3.1863-1872.1996 · Cited by 304
The growth and potential of human antiviral monoclonal antibody therapeutics
Marasco, W. A., & Sui, J. (2007) · Nature Biotechnology · doi:10.1038/nbt1363 · Cited by 294
Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies
Zhu, Z., Chakraborti, S., He, Y., Roberts, A., Sheahan, T., Xiao, X., Hensley, L. E., Prabakaran, P., Rockx, B., Sidorov, I. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701000104 · Cited by 284
Self-citationDeming, D., Sheahan, T. P., Heise, M. T., Yount, B. L., Davis, N., Sims, A. M., Suthar, M. S., Harkema, J. R., Whitmore, A. C., Pickles, R. J., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030525 · Cited by 273
Self-citationHuman monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets
ter Meulen, J., Bakker, A. B. H., van den Brink, E. N., Weverling, G. J., Martina, B. E. E., Haagmans, B. L., Kuiken, T., de Kruif, J., Preiser, W., Spaan, W. J. M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16506-9 · Cited by 266
Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses
Yang, Z., Werner, H. C., Kong, W., Leung, K., Traggiai, E., Lanzavecchia, A., & Nabel, G. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409065102 · Cited by 250
Self-citationPrabakaran, P., Gan, J., Feng, Y., Zhu, Z., Choudhry, V., Xiao, X., Ji, X., & Dimitrov, D. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600697200 · Cited by 235
Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza
Simmons, C. P., Bernasconi, N. L., Suguitan, A. L., Mills, K., Ward, J. M., Châu, N. V. V., Hien, T. T., Sallusto, F., Ha, D. Q., Farrar, J., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040178 · Cited by 209
Self-citationRoberts, A., Paddock, C. D., Vogel, L., Butler, E. L., Zaki, S. R., & Subbarao, K. (2005) · Journal of Virology · doi:10.1128/jvi.79.9.5833-5838.2005 · Cited by 196
Hwang, W. C., Lin, Y., Santelli, E., Sui, J., Jaroszewski, L., Stec, B., Farzan, M., Marasco, W. A., & Liddington, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603275200 · Cited by 195
Kaverin, N. V., Rudneva, I. A., Ilyushina, N. A., Varich, N. L., Lipatov, A. S., Smirnov, Y. A., Govorkova, E. A., Калмановна, Г. А., Dk, L., & Webster, R. G. (2002) · Journal of General Virology · doi:10.1099/0022-1317-83-10-2497 · Cited by 187
Immunosenescence: Role and measurement in influenza vaccine response among the elderly
Targonski, P. V., Jacobson, R. M., & Poland, G. A. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.01.025 · Cited by 186
Nelson, J. D., Brunel, F. M., Jensen, R., Crooks, E. T., Cardoso, R. M. F., Wang, M., Hessell, A. J., Wilson, I. A., Binley, J. Μ., Dawson, P. E., et al. (2007) · Journal of Virology · doi:10.1128/jvi.02588-06 · Cited by 175
Laboratory-Acquired Severe Acute Respiratory Syndrome
Lim, P. L., Kurup, A., Gopalakrishna, G., Chan, K. P., Wong, C. W., Ng, L. C., Se-Thoe, S. Y., Oon, L. L. E., Bai, X., Stanton, L. W., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032565 · Cited by 170
Greenough, T. C., Babcock, G. J., Roberts, A., Hernández, H. J., Thomas, W. D., Coccia, J. A., Graziano, R. F., Srinivasan, M., Lowy, I., Finberg, R. W., et al. (2005) · The Journal of Infectious Diseases · doi:10.1086/427242 · Cited by 156
Bakker, A. B. H., Marissen, W. E., Kramer, R. A., Papaneri, A. B., Weldon, W. C., Niezgoda, M., Hanlon, C. A., Thijsse, S., Backus, H. H. J., de Kruif, J., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.14.9062-9068.2005 · Cited by 155
Sui, J., Li, W., Roberts, A., Matthews, L. J., Murakami, A., Vogel, L., Wong, S. K., Subbarao, K., Farzan, M., & Marasco, W. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.10.5900-5906.2005 · Cited by 153
Expression cloning of functional receptor used by SARS coronavirus
Wang, P., Chen, J., Zheng, A., Nie, Y., Shi, X., Wang, W., Wang, G., Luo, M., Liu, H., Tan, L., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.01.076 · Cited by 146
Nie, Y., Wang, G., Shi, X., Zhang, H., Yan, Q., Zhong-ping, H., Wei, W., Lian, G., Yin, X., Du, L., et al. (2004) · The Journal of Infectious Diseases · doi:10.1086/423286 · Cited by 146
Coronaviridaeand SARS-associated Coronavirus Strain HSR1
Vicenzi, E., Canducci, F., Pinna, D., Mancini, N., Carletti, S., Lazzarin, A., Bordignon, C., Poli, G., & Clementi, M. (2004) · Emerging infectious diseases · doi:10.3201/eid1003.030683 · Cited by 132
Antibodies for the prevention and treatment of viral diseases
Sawyer, L. A. (2000) · Antiviral Research · doi:10.1016/s0166-3542(00)00111-x · Cited by 127
Day, P. M., Thompson, C. D., Buck, C. B., Pang, Y.-Y. S., Lowy, D. R., & Schiller, J. T. (2007) · Journal of Virology · doi:10.1128/jvi.00552-07 · Cited by 118
He, Y., Li, J., Li, W., Lustigman, S., Farzan, M., & Jiang, S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.10.6085 · Cited by 118
Roberts, A., Thomas, W. D., Guarner, J., Lamirande, E. W., Babcock, G. J., Greenough, T. C., Vogel, L., Hayes, N., Sullivan, J. L., Zaki, S. R., et al. (2006) · The Journal of Infectious Diseases · doi:10.1086/500143 · Cited by 103
Wien, M. W., Filman, D. J., Stura, E. A., Guillot, S., Delpeyroux, F., Crainic, R., & Hogle, J. M. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0395-232 · Cited by 78
Chan, K. A. A., Tang, N., Hui, D. S. C., Chung, G. T., Wu, A. K. L., Chim, S. S. C., Chiu, R., Lee, N., Choi, K.-W., Sung, Y. M., et al. (2005) · BMC Infectious Diseases · doi:10.1186/1471-2334-5-26 · Cited by 64
Magnusson, B. M., Cross, S. E., Winckle, G., & Roberts, M. S. (2006) · Skin Pharmacology and Physiology · doi:10.1159/000095254 · Cited by 62
Rockx, B., Sheahan, T. P., Donaldson, E., Harkema, J. R., Sims, A. M., Heise, M. T., Pickles, R. J., Cameron, M. J., Kelvin, D. J., & Baric, R. S. (2007) · Journal of Virology · doi:10.1128/jvi.00505-07 · Cited by 62
Self-citationLai, S.-C., Chong, P. C.-S., Yeh, C., Liu, L. S.-J., Jan, J., Chi, H.-Y., Liu, H.-W., Chen, A., & Wang, Y.-C. (2005) · Journal of Biomedical Science · doi:10.1007/s11373-005-9004-3 · Cited by 60
Laboratory-acquired SARS raises worries on biosafety
Orellana, C. (2004) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(04)00911-9 · Cited by 60
Tripp, R. A., Haynes, L. M., Moore, D. D., Anderson, B. C., Tamin, A., Harcourt, B. H., Jones, L. P., Yilla, M., Babcock, G. J., Greenough, T. C., et al. (2005) · Journal of Virological Methods · doi:10.1016/j.jviromet.2005.03.021 · Cited by 58
Sheng, W., Chiang, B., Chang, S., Ho, H.-N., Wang, J., Chen, Y., Hsiao, C.-H., Hseuh, P.-R., Chie, W., & Yang, P. (2005) · PubMed · Cited by 51
Coronaviruses: Molecular and Cellular Biology
Thiel, V. (2020) · Cited by 39
Neutralizing human monoclonal antibodies to hepatitis A virus recovered by phage display
Kim, S. J., Jang, M. H., Stapleton, J. T., Yoon, S. O., Kim, K., Jeon, E., & Hong, H. J. (2003) · Virology · doi:10.1016/j.virol.2003.10.014 · Cited by 29
Vogel, L., Roberts, A., Paddock, C. D., Genrich, G. L., Lamirande, E. W., Kapadia, S. U., Rose, J. K., Zaki, S. R., & Subbarao, K. (2006) · Vaccine · doi:10.1016/j.vaccine.2006.11.055 · Cited by 25
Epitope Mapping of Recombinant Hepatitis B Surface Antigen by Murine Monoclonal Antibodies
Roohi, A., Khoshnoodi, J., Zarnani, A., & Shokri, F. (2005) · Hybridoma · doi:10.1089/hyb.2005.24.71 · Cited by 18
Sars Coronavirus Vaccine Development
Baric, R. S., Sheahan, T. P., Deming, D., Donaldson, E., Yount, B. L., Sims, A. M., Roberts, R., Frieman, M. B., & Rockx, B. (2006) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-33012-9_101 · Cited by 17
Self-citationRisk factors for SARS-related deaths in 2003, Beijing.
Liu, M., Liang, W. N., Chen, Q., Xie, X.-Q., Wu, J., He, X., & Liu, Z.-J. (2006) · PubMed · Cited by 15
Epitope Mapping by Antibody Competition: Methodology and Evaluation of the Validity of the Technique
Tzartos, S. J. (2003) · Humana Press eBooks · doi:10.1385/0-89603-375-9:55 · Cited by 5
Yang, X., Lipchina, I., Lifton, M. A., Wang, L., & Sodroski, J. (2007) · Journal of Virology · doi:10.1128/jvi.00394-07 · Cited by 4
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Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Pinto, D., Park, Y.-J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., Jaconi, S., Culap, K., Zatta, F., De Marco, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2349-y · Cited by 1,885
Self-citationThe spike protein of SARS-CoV — a target for vaccine and therapeutic development
Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B.-J., & Jiang, S. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2090 · Cited by 1,678
From SARS to MERS, Thrusting Coronaviruses into the Spotlight
Song, Z., Xu, Y., Bao, L., Zhang, L., Yü, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., & Qin, C. (2019) · Viruses · doi:10.3390/v11010059 · Cited by 1,292
Potently neutralizing and protective human antibodies against SARS-CoV-2
Zost, S. J., Gilchuk, P., Case, J. B., Binshtein, E., Chen, R. E., Nkolola, J. P., Schäfer, A., Reidy, J. X., Trivette, A., Nargi, R. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2548-6 · Cited by 1,041
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Metadata
- Authors
- Rockx, B., Corti, D., Donaldson, E., Sheahan, T., Stadler, K., Lanzavecchia, A., & Baric, R.
- Affiliations
- Department of Epidemiology
- Institute for Research in Biomedicine (CH)
- University of North Carolina at Chapel Hill (US)
- Novartis (Italy) (IT)
- Corresponding author
- Baric, Ralph
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2008-04
- Volume
- 82
- Issue
- 7
- Pages
- 3220-3235
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2268459
- OpenAlex
- W2155387067
- Cited by
- 134
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 18 · 2020: 49 · 2019: 6 · 2017: 3 · 2015: 4 · 2014: 6 · 2013: 1 · 2012: 4
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UNC Libraries
- Funders
- European Commission
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (P01-AI059136, R01AI059136, P01AI059443)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV, monoclonal antibodies, cross-neutralization, spike protein, passive immunization, antibody escape mutants, epitope mapping, antibody cocktail
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibodies, Viral, Body Weight, Cross Reactions, Female, Humans, Immunization, Passive, Lung, Membrane Glycoproteins, Mice, Inbred BALB C, Models, Molecular, Neutralization Tests, Viral Envelope Proteins, Survival Analysis, Epitope Mapping, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Spike Glycoprotein, Coronavirus
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