RT Journal Article
SR Electronic
T1 Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.19.476998
DO 10.1101/2022.01.19.476998
A1 J. Andrew Duty
A1 Thomas Kraus
A1 Heyue Zhou
A1 Yanliang Zhang
A1 Namir Shaabani
A1 Soner Yildiz
A1 Na Du
A1 Alok Singh
A1 Lisa Miorin
A1 Donghui Li
A1 Karen Stegman
A1 Sabrina Ophir
A1 Xia Cao
A1 Kristina Atanasoff
A1 Reyna Lim
A1 Shreyas Kowdle
A1 Juan Manuel Carreño
A1 Laura Rivero-Nava
A1 Ariel Raskin
A1 Elena Moreno
A1 Sachi Johnson
A1 Raveen Rathnasinghe
A1 Chin I Pai
A1 Thomas Kehrer
A1 Elizabeth Paz Cabral
A1 Sonia Jangra
A1 Laura Healy
A1 Gagandeep Singh
A1 Prajakta Warang
A1 Viviana Simon
A1 Mia Emilia Sordillo
A1 Harm van Bakel
A1 Yonghong Liu
A1 Weina Sun
A1 Lisa Kerwin
A1 Peter Palese
A1 John Teijaro
A1 Michael Schotsaert
A1 Florian Krammer
A1 Damien Bresson
A1 Adolfo García-Sastre
A1 Yanwen Fu
A1 Benhur Lee
A1 Colin Powers
A1 Thomas Moran
A1 Henry Ji
A1 Domenico Tortorella
A1 Robert Allen
YR 2022
UL http://biorxiv.org/content/early/2022/01/20/2022.01.19.476998.abstract
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.