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Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants.
Duty, J Andrew; Kraus, Thomas; Zhou, Heyue; Zhang, Yanliang; Shaabani, Namir; Yildiz, Soner; Du, Na; Singh, Alok; Miorin, Lisa; Li, Donghui; Stegman, Karen; Ophir, Sabrina; Cao, Xia; Atanasoff, Kristina; Lim, Reyna; Mena, Ignacio; Bouvier, Nicole M; Kowdle, Shreyas; Carreño, Juan Manuel; Rivero-Nava, Laura; Raskin, Ariel; Moreno, Elena; Johnson, Sachi; Rathnasinghe, Raveen; Pai, Chin I; Kehrer, Thomas; Cabral, Elizabeth Paz; Jangra, Sonia; Healy, Laura; Singh, Gagandeep; Warang, Prajakta; Simon, Viviana; Sordillo, Emilia Mia; van Bakel, Harm; Liu, Yonghong; Sun, Weina; Kerwin, Lisa; Teijaro, John; Schotsaert, Michael; Krammer, Florian; Bresson, Damien; García-Sastre, Adolfo; Fu, Yanwen; Lee, Benhur; Powers, Colin; Moran, Thomas; Ji, Henry; Tortorella, Domenico; Allen, Robert.
Afiliación
  • Duty JA; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Center for Therapeutic Antibody Development, Drug Discovery Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Kraus T; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Center for Therapeutic Antibody Development, Drug Discovery Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Zhou H; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Zhang Y; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Shaabani N; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Yildiz S; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Du N; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Singh A; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Miorin L; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Li D; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Stegman K; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Ophir S; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Cao X; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Atanasoff K; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lim R; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Mena I; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Bouvier NM; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Kowdle S; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Carreño JM; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Rivero-Nava L; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Raskin A; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Moreno E; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Johnson S; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Rathnasinghe R; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Pai CI; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Kehrer T; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Cabral EP; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Jangra S; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Healy L; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Singh G; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Warang P; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Simon V; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York,
  • Sordillo EM; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • van Bakel H; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Liu Y; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Sun W; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Kerwin L; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Teijaro J; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schotsaert M; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bresson D; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • García-Sastre A; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York,
  • Fu Y; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Lee B; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Powers C; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
  • Moran T; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Center for Therapeutic Antibody Development, Drug Discovery Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Ji H; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA. Electronic address: hji@sorrentotherapeutics.com.
  • Tortorella D; Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA; Center for Therapeutic Antibody Development, Drug Discovery Institute, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Allen R; Sorrento Therapeutics, Inc., San Diego, CA 92121, USA.
Med ; 3(10): 705-721.e11, 2022 10 14.
Article en En | MEDLINE | ID: mdl-36044897
BACKGROUND: The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant and its BA.X lineages, has rendered ineffective a number of previously FDA emergency use authorized SARS-CoV-2 neutralizing antibody therapies. Furthermore, those approved antibodies with neutralizing activity against Omicron BA.1 are reportedly ineffective against the subset of Omicron subvariants that contain a R346K substitution, BA.1.1, and the more recently emergent BA.2, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. METHODS: Following a campaign of antibody discovery based on the vaccination of Harbor H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. FINDINGS: STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against each of the tested Omicron subvariants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. CONCLUSIONS: With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for intravenous or intranasal use in human clinical trials. FUNDING: Funded by CRIPT (no. 75N93021R00014), DARPA (HR0011-19-2-0020), and NCI Seronet (U54CA260560).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Neutralizantes / Tratamiento Farmacológico de COVID-19 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Med Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Neutralizantes / Tratamiento Farmacológico de COVID-19 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Med Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos