Journal
ISCIENCE
Volume 24, Issue 7, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102699
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Funding
- NIH NCI award [T32 CA09171]
- NIH NIAID [T32-AI-055400]
- CEPI/Inovio Pharmaceuticals
- Wistar Institute COVID-19 science discovery fund
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A mouse model for SARS-CoV-2 infection based on AAV6.2FF-hACE2 transduction of the respiratory tract was developed and validated, showing promising results in vaccine testing. This genetically diverse mouse model represents a valuable tool for preclinical evaluation of interventions against SARS-CoV-2.
More than 100 million people have been infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Common laboratory mice are not susceptible to wild-type SARS-CoV-2 infection, challenging the development and testing of effective interventions. Here, we describe the development and testing of a mouse model for SARS-CoV-2 infection based on transduction of the respiratory tract of laboratory mice with an adeno-associated virus vector (AAV6) expressing human ACE-2 (AAV6.2FF-hACE2). We validated this model using a previously described synthetic DNA vaccine plasmid, INO-4800 (pS). Intranasal instillation of AAV6.2FF-hACE2 resulted in robust hACE2 expression in the respiratory tract. pS induced robust cellular and humoral responses. Vaccinated animals were challenged with 10(5) TCID50 SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) and euthanized four days post-challenge to assess viral load. One immunization resulted in 50% protection and two immunizations were completely protective. Overall, the AAV6.2FF-hACE2 mouse transduction model represents an easily accessible, genetically diverse mouse model for wild-type SARS-CoV-2 infection and preclinical evaluation of potential interventions.
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