Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters
Abstract
Animal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 08, 2020
- Accession Number
- AD1108652
Entities
People
- Dave Gangem
- Jacob Glanville
- Janice A. Williams
- Jay W. Hooper
- Jeffrey M. Smith
- Joseph W. Golden
- Lucia M. Principe
- Rebecca L. Brocato
- Robert K. Kim
- Rong Li
- Sawsan Youssef
- Xiankun Zeng
- Yanan Liu
- Zhongde Wang
Organizations
- United States Army Medical Research Institute of Infectious Diseases
- Utah State University