Journal Article Preprint Epublish
PubMed: 40791410 DOI: 10.1101/2025.07.16.665104
Mouse Adapted Omicron BA.5 Induces A Fibrotic Lung Disease Phenotype in BALB/c Mice.
bioRxiv
Authors: John M Powers, Sarah R Leist, Naveenchandra Suryadevara, Seth J Zost, Elad Binshtein, Anfal Abdelgadir, Michael L Mallory, Caitlin E Edwards, Kendra L Gully, Miranda L Hubbard, Mark R Zweigart, Alexis B Bailey, Timothy P Sheahan, James E Crowe, Stephanie A Montgomery, Jack R Harkema, Ralph S Baric
Affiliations
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA.
Abstract
Following SARS-CoV-2 Omicron BA.1, subsequent Omicron sub-lineages have continued to emerge, challenging the development of intervention and prevention strategies, including monoclonal antibodies and vaccines. To better understand the pathogenic effects caused by Omicron BA.5 infection, we developed a mouse-adapted virus with overt disease burden in BALB/c mice. Acute disease was characterized by significant weight loss and lung dysfunction following high-dose challenges. In survivor animals that were followed through 107 days post-infection, subpleural fibrosis with associated tertiary lymphoid structures was noted. Serum from these mice demonstrated potent neutralization against BA.5, with substantially reduced neutralization titers against early epidemic, zoonotic, and more recent contemporary XBB.1.5 variants. Intervention with pre-clinical monoclonal antibodies revealed that robust protection from BA.5-induced lung disease was possible after prophylactic administration. Together, this model enables the investigation of therapeutic approaches for both acute and post-acute sequelae of COVID-19.
MeSH
Lung, Antibodies, Phenotype, Antibodies, Monoclonal, Lung Diseases, Infections