Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants
J Andrew Duty, Thomas Kraus, Heyue Zhou, Yanliang Zhang, Namir Shaabani, Soner Yildiz, Na Du, Alok Singh, Lisa Miorin, Donghui Li, Karen Stegman, Sabrina Ophir, Xia Cao, Kristina Atanasoff, Reyna Lim, Ignacio Mena, Nicole M Bouvier, Shreyas Kowdle, Juan Manuel Carreño, Laura Rivero-Nava, Ariel Raskin, Elena Moreno, Sachi Johnson, Raveen Rathnasinghe, Chin I Pai, Thomas Kehrer, Elizabeth Paz Cabral, Sonia Jangra, Laura Healy, Gagandeep Singh, Prajakta Warang, Viviana Simon, Emilia Mia Sordillo, Harm Van Bakel, Yonghong Liu, Weina Sun, Lisa Kerwin, John Teijaro, Michael Schotsaert, Florian Krammer, Damien Bresson, Adolfo García-Sastre, Yanwen Fu, Benhur Lee, Colin Powers, Thomas Moran, Henry Ji, Domenico Tortorella, Robert Allen
Med, doi:10.1016/j.medj.2022.08.002
The burden of COVID-19 and the emergence of virus variants necessitates continued exploration of neutralizing antibody therapies and methods of treatment. Duty et al. identify a human monoclonal antibody that neutralizes recently described SARS-CoV-2 variants and, when administered intranasally or intravenously, offers protection in a mouse model of SARS-CoV-2 disease.
Detailed methods are provided in the online version of this paper and include the following:
SUPPLEMENTAL INFORMATION Supplemental information can be found online at https://doi.org/10.1016/j.medj. 2022.08.002.
AUTHOR CONTRIBUTIONS
DECLARATION OF INTERESTS The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, and Pfizer, outside of the reported work. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting..
References
Aggarwal, Stella, Walker, Akerman, Milogiannakis et al., SARS-CoV-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern,
doi:10.1101/2021.12.14.21267772Ahn, Shin, Kim, Lee, Kim et al., Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19), J. Microbiol. Biotechnol,
doi:10.4014/jmb.2003.03011Cameroni, Saliba, Bowen, Rosen, Culap et al., Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift,
doi:10.1101/2021.12.12.472269Cao, Maruyama, Zhou, Kerwin, Sattler et al., Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach,
doi:10.1101/2020.09.27.316174Cobb, Nkolola, Gilchuk, Chandrashekar, Yu et al., A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in cynomolgus macaques, Med,
doi:10.1016/j.medj.2022.01.004Diamond, Halfmann, Maemura, Iwatsuki-Horimoto, Iida et al., The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters, Res. Sq,
doi:10.21203/rs.3.rs-1211792/v1Donoghue, Hsieh, Baronas, Godbout, Gosselin et al., A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9, Circ. Res,
doi:10.1161/01.res.87.5.e1Elbe, Buckland-Merrett, Data, disease and diplomacy: GISAID's innovative contribution to global health, Glob. Chall,
doi:10.1002/gch2.1018Fu, Maruyama, Singh, Lim, Ledesma et al., Protective effects of STI-2020 antibody delivered postinfection by the intranasal or intravenous route in a Syrian golden hamster COVID-19 model,
doi:10.1101/2020.10.28.359836Gardner, Stein, Duty, Schwarz, Noriega et al., Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein, Nat. Commun,
doi:10.1038/ncomms13627Gupta, Gonzalez-Rojas, Juarez, Crespo Casal, Moya et al., Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab, N. Engl. J. Med,
doi:10.1056/NEJMoa2107934Halwe, Kupke, Vanshylla, Liberta, Gruell et al., Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection, Viruses
Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, J. Pathol,
doi:10.1002/path.1570Hansen, Baum, Pascal, Russo, Giordano et al., Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail, Science,
doi:10.1126/science.abd0827Harmer, Gilbert, Borman, Clark, Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme, FEBS Lett,
doi:10.1016/s0014-5793(02)03640-2Hoffmann, Kru ¨ger, Schulz, Cossmann, Rocha et al., The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic, Cell,
doi:10.1016/j.cell.2021.12.032Ikegame, Siddiquey, Hung, Haas, Brambilla et al., Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants, Nat. Commun,
doi:10.1038/s41467-021-24909-9(2021Korber, Fischer, Gnanakaran, Yoon, Theiler et al., Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus, Cell,
doi:10.1038/s41577-020-00434-6Leyva-Grado, Tan, Leon, Yondola, Palese, Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies, Antimicrob. Agents Chemother,
doi:10.1128/aac.00290-15Li, Edwards, Manne, Martinez, Scha ¨fer et al., In vitro and in vivo functions of SARS-CoV-2 infectionenhancing and neutralizing antibodies, Cell,
doi:10.1128/aac.00290-15Lu, Hwang, Liu, Lee, Tsai et al., Development of therapeutic antibodies for the treatment of diseases, J. Biomed. Sci,
doi:10.1186/s12929-019-0592-zMcmahan, Giffin, Tostanoski, Chung, Siamatu et al., Reduced pathogenicity of the SARS-CoV-2 omicron variant in hamsters,
doi:10.1101/2022.01.02.474743Mullen, Latif, Alkuzweny, Cano, Haag et al., None
Piepenbrink, Park, Oladunni, Deshpande, Basu et al., Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters, Cell Rep. Med,
doi:10.1038/s41467-020-15562-9(2021Pinto, Park, Beltramello, Walls, Tortorici et al., Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody, Nature,
doi:10.1038/s41586-020-2349-yPlanas, Saunders, Maes, Guivel-Benhassine, Planchais et al., Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization,
doi:10.1101/2021.12.14.472630Poh, Carissimo, Wang, Amrun, Lee et al., Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients, Nat. Commun,
doi:10.1038/s41467-020-16638-2Pulliam, Van Schalkwyk, Govender, Gottberg, Cohen et al., Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa,
doi:10.1101/2021.11.11.21266068Radvak, Kwon, Kosikova, Ortega-Rodriguez, Xiang et al., SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains, Nat. Commun,
doi:10.1038/s41467-021-26803-w(2021Schlothauer, Herter, Koller, Grau-Richards, Steinhart et al., Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions, Protein Eng. Des. Sel,
doi:10.1093/protein/gzw040Scott, Hsiao, Moyo, Singh, Tegally et al., None
Shi, Shan, Duan, Chen, Liu et al., A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2, Nature,
doi:10.1038/s41586-020-2381-yTan, O'dell, Hernandez, Sordillo, Kahn et al., Human anti-neuraminidase antibodies reduce airborne transmission of clinical influenza virus isolates in the Guinea pig model, J. Virol,
doi:10.1128/jvi.01421-21Uriu, Kimura, Shirakawa, Takaori-Kondo, Nakada et al., Neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine serum, N. Engl. J. Med,
doi:10.1056/NEJMc2114706Vanblargan, Errico, Halfmann, Zost, Crowe et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies,
doi:10.1101/2021.12.15.472828Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2035002Weltzin, Hsu, Mittler, Georgakopoulos, Monath, Intranasal monoclonal immunoglobulin A against respiratory syncytial virus protects against upper and lower respiratory tract infections in mice, Antimicrob. Agents Chemother,
doi:10.1128/aac.38.12.2785Weltzin, Monath, Intranasal antibody prophylaxis for protection against viral disease, Clin. Microbiol. Rev,
doi:10.1128/CMR.12.3.383Weltzin, Traina-Dorge, Soike, Zhang, Mack et al., Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection, J. Infect. Dis,
doi:10.1093/infdis/174.2.256Westendorf, Zentelis, Wang, Foster, Vaillancourt et al., None
Widjaja, Wang, Van Haperen, Gutie ´rrez-A ´lvarez, Van Dieren et al., Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein, Emerg. Microbes Infect,
doi:10.1080/22221751.2019.1597644Winkler, Bailey, Kafai, Nair, Mccune et al., SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function, Nat. Immunol,
doi:10.1038/s41590-020-0778-2Yinda, Port, Bushmaker, Offei Owusu, Purushotham et al., K18-hACE2 mice develop respiratory disease resembling severe COVID-19, PLoS Pathog,
doi:10.1371/journal.ppat.1009195Zhang, Yang, Xiang, Cui, Liu et al., Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice,
doi:10.1101/2020.12.08.416677Zhu, Zhang, Wang, Li, Yang et al., A novel coronavirus from patients with pneumonia in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2001017{ 'indexed': {'date-parts': [[2022, 8, 8]], 'date-time': '2022-08-08T23:12:30Z', 'timestamp': 1660000350255},
'reference-count': 0,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2022, 8, 1]],
'date-time': '2022-08-01T00:00:00Z',
'timestamp': 1659312000000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}],
'content-domain': { 'domain': ['cell.com', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2022, 8]]},
'DOI': '10.1016/j.medj.2022.08.002',
'type': 'journal-article',
'created': {'date-parts': [[2022, 8, 8]], 'date-time': '2022-08-08T22:51:32Z', 'timestamp': 1659999092000},
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Discovery and Intranasal Administration of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody '
'with Activity against multiple Omicron sub variants',
'prefix': '10.1016',
'author': [ {'given': 'J. Andrew', 'family': 'Duty', 'sequence': 'first', 'affiliation': []},
{'given': 'Thomas', 'family': 'Kraus', 'sequence': 'additional', 'affiliation': []},
{'given': 'Heyue', 'family': 'Zhou', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yanliang', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []},
{'given': 'Namir', 'family': 'Shaabani', 'sequence': 'additional', 'affiliation': []},
{'given': 'Soner', 'family': 'Yildiz', 'sequence': 'additional', 'affiliation': []},
{'given': 'Na', 'family': 'Du', 'sequence': 'additional', 'affiliation': []},
{'given': 'Alok', 'family': 'Singh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Lisa', 'family': 'Miorin', 'sequence': 'additional', 'affiliation': []},
{'given': 'Donghui', 'family': 'Li', 'sequence': 'additional', 'affiliation': []},
{'given': 'Karen', 'family': 'Stegman', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sabrina', 'family': 'Ophir', 'sequence': 'additional', 'affiliation': []},
{'given': 'Xia', 'family': 'Cao', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kristina', 'family': 'Atanasoff', 'sequence': 'additional', 'affiliation': []},
{'given': 'Reyna', 'family': 'Lim', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ignacio', 'family': 'Mena', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nicole M.', 'family': 'Bouvier', 'sequence': 'additional', 'affiliation': []},
{'given': 'Shreyas', 'family': 'Kowdle', 'sequence': 'additional', 'affiliation': []},
{'given': 'Juan Manuel', 'family': 'Carreño', 'sequence': 'additional', 'affiliation': []},
{'given': 'Laura', 'family': 'Rivero-Nava', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ariel', 'family': 'Raskin', 'sequence': 'additional', 'affiliation': []},
{'given': 'Elena', 'family': 'Moreno', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sachi', 'family': 'Johnson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Raveen', 'family': 'Rathnasinghe', 'sequence': 'additional', 'affiliation': []},
{'given': 'Chin I.', 'family': 'Pai', 'sequence': 'additional', 'affiliation': []},
{'given': 'Thomas', 'family': 'Kehrer', 'sequence': 'additional', 'affiliation': []},
{'given': 'Elizabeth Paz', 'family': 'Cabral', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sonia', 'family': 'Jangra', 'sequence': 'additional', 'affiliation': []},
{'given': 'Laura', 'family': 'Healy', 'sequence': 'additional', 'affiliation': []},
{'given': 'Gagandeep', 'family': 'Singh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Prajakta', 'family': 'Warang', 'sequence': 'additional', 'affiliation': []},
{'given': 'Viviana', 'family': 'Simon', 'sequence': 'additional', 'affiliation': []},
{'given': 'Emilia Mia', 'family': 'Sordillo', 'sequence': 'additional', 'affiliation': []},
{'given': 'Harm', 'family': 'van Bakel', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yonghong', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []},
{'given': 'Weina', 'family': 'Sun', 'sequence': 'additional', 'affiliation': []},
{'given': 'Lisa', 'family': 'Kerwin', 'sequence': 'additional', 'affiliation': []},
{'given': 'John', 'family': 'Teijaro', 'sequence': 'additional', 'affiliation': []},
{'given': 'Michael', 'family': 'Schotsaert', 'sequence': 'additional', 'affiliation': []},
{'given': 'Florian', 'family': 'Krammer', 'sequence': 'additional', 'affiliation': []},
{'given': 'Damien', 'family': 'Bresson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Adolfo', 'family': 'García-Sastre', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yanwen', 'family': 'Fu', 'sequence': 'additional', 'affiliation': []},
{'given': 'Benhur', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []},
{'given': 'Colin', 'family': 'Powers', 'sequence': 'additional', 'affiliation': []},
{'given': 'Thomas', 'family': 'Moran', 'sequence': 'additional', 'affiliation': []},
{'given': 'Henry', 'family': 'Ji', 'sequence': 'additional', 'affiliation': []},
{'given': 'Domenico', 'family': 'Tortorella', 'sequence': 'additional', 'affiliation': []},
{'given': 'Robert', 'family': 'Allen', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'container-title': 'Med',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S266663402200321X?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S266663402200321X?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2022, 8, 8]],
'date-time': '2022-08-08T22:51:32Z',
'timestamp': 1659999092000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S266663402200321X'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 8]]},
'references-count': 0,
'alternative-id': ['S266663402200321X'],
'URL': 'http://dx.doi.org/10.1016/j.medj.2022.08.002',
'relation': {},
'ISSN': ['2666-6340'],
'subject': ['General Medicine'],
'container-title-short': 'Med',
'published': {'date-parts': [[2022, 8]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Discovery and Intranasal Administration of a SARS-CoV-2 Broadly-Acting '
'Neutralizing Antibody with Activity against multiple Omicron sub variants',
'name': 'articletitle',
'label': 'Article Title'},
{'value': 'Med', 'name': 'journaltitle', 'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.medj.2022.08.002',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{'value': '© 2022 Elsevier Inc.', 'name': 'copyright', 'label': 'Copyright'}]}
