PT  - JOURNAL ARTICLE
AU  - J. Andrew Duty
AU  - Thomas Kraus
AU  - Heyue Zhou
AU  - Yanliang Zhang
AU  - Namir Shaabani
AU  - Soner Yildiz
AU  - Na Du
AU  - Alok Singh
AU  - Lisa Miorin
AU  - Donghui Li
AU  - Karen Stegman
AU  - Sabrina Ophir
AU  - Xia Cao
AU  - Kristina Atanasoff
AU  - Reyna Lim
AU  - Shreyas Kowdle
AU  - Juan Manuel Carreño
AU  - Laura Rivero-Nava
AU  - Ariel Raskin
AU  - Elena Moreno
AU  - Sachi Johnson
AU  - Raveen Rathnasinghe
AU  - Chin I Pai
AU  - Thomas Kehrer
AU  - Elizabeth Paz Cabral
AU  - Sonia Jangra
AU  - Laura Healy
AU  - Gagandeep Singh
AU  - Prajakta Warang
AU  - Viviana Simon
AU  - Mia Emilia Sordillo
AU  - Harm van Bakel
AU  - Yonghong Liu
AU  - Weina Sun
AU  - Lisa Kerwin
AU  - Peter Palese
AU  - John Teijaro
AU  - Michael Schotsaert
AU  - Florian Krammer
AU  - Damien Bresson
AU  - Adolfo García-Sastre
AU  - Yanwen Fu
AU  - Benhur Lee
AU  - Colin Powers
AU  - Thomas Moran
AU  - Henry Ji
AU  - Domenico Tortorella
AU  - Robert Allen
TI  - Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants
AID  - 10.1101/2022.01.19.476998
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.19.476998
4099  - http://biorxiv.org/content/early/2022/01/20/2022.01.19.476998.short
4100  - http://biorxiv.org/content/early/2022/01/20/2022.01.19.476998.full
AB  - 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 therapeutic 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.Competing Interest StatementThe 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.