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Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants [article]

J. Andrew Duty, Thomas A Kraus, Heyue Zhou, Yanliang Zhang, Namir Shaabani, Soner Yildiz, Na Du, Alok Singh, Lisa Miorin, Donghui Li, Karen Stegman, Sabrina I Ophir (+36 others)
2022 bioRxiv   pre-print

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https://web.archive.org/web/20220126161453/https://www.biorxiv.org/content/biorxiv/early/2022/01/20/2022.01.19.476998.full.pdf

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The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate
more » ... eutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour 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. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants 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. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.
doi:10.1101/2022.01.19.476998 fatcat:gr4mza2ku5asvcny4pkf4i6b24
Citation

J. Andrew Duty, Thomas A Kraus, Heyue Zhou, Yanliang Zhang, Namir Shaabani, Soner Yildiz, Na Du, Alok Singh, Lisa Miorin, Donghui Li, Karen Stegman, Sabrina I Ophir, Xia Cao, Kristina Atanasoff, Reyna Lim, Shreyas S Kowdle, Juan Manuel Carreno, Laura Rivero-Nava, Ariel Raskin, Elena Moreno, Sachi Johnson, Raveen Rathnasinghe, Chin I Pai, Thomas Kehrer, Elizabeth Paz Cabral, Sonia Jangra, Laura D Healy, Gagandeep Singh, Prajakta Warang, Viviana Simon, Mia Emilia Sordillo, Harm van Bakel, Yonghong Liu, Weina Sun, Lisa Kerwin, Peter Palese, John Teijaro, Michael Schotsaert, Florian Krammer, Damien Bresson, Adolfo Garcia-Sastre, Yanwen Fu, Benhur Lee, Colin Powers, Thomas M Moran, Henry Ji, Domenico Tortorella, Robert D Allen. "Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants." bioRxiv (2022)