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Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters
Preprint
in English
| bioRxiv
| ID: ppbiorxiv-161612
Journal article
A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See journal article
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. One Sentence SummaryAn antibody targeting the spike protein of SARS-CoV-2 limits infection in immunosuppressed Syrian hamster models.
cc_no
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Type of study:
Experimental_studies
/
Prognostic study
Language:
English
Year:
2020
Document type:
Preprint