A novel mouse AAV6 hACE2 transduction model of wild-type SARS-CoV-2 infection studied using synDNA immunogens
Ebony N. Gary,
Bryce M. Warner,
Elizabeth M. Parzych,
Bryan D. Griffin,
Xizhou Zhu,
Nikesh Tailor,
Nicholas J. Tursi,
Mable Chan,
Mansi Purwar,
Robert Vendramelli,
Jihae Choi,
Kathy L. Frost,
Sophia Reeder,
Kevin Liaw,
Edgar Tello,
Ali R. Ali,
Kun Yun,
Yanlong Pei,
Sylvia P. Thomas,
Amira D. Rghei,
Matthew M. Guilleman,
Kar Muthumani,
Trevor Smith,
Sarah K. Wootton,
Ami Patel,
David B. Weiner,
Darwyn Kobasa
Affiliations
Ebony N. Gary
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Bryce M. Warner
Public Health Agency of Canada, Winnipeg, MB, Canada
Elizabeth M. Parzych
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Bryan D. Griffin
Public Health Agency of Canada, Winnipeg, MB, Canada
Xizhou Zhu
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Nikesh Tailor
Public Health Agency of Canada, Winnipeg, MB, Canada
Nicholas J. Tursi
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Mable Chan
Public Health Agency of Canada, Winnipeg, MB, Canada
Mansi Purwar
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Robert Vendramelli
Public Health Agency of Canada, Winnipeg, MB, Canada
Jihae Choi
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Kathy L. Frost
Public Health Agency of Canada, Winnipeg, MB, Canada
Sophia Reeder
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Kevin Liaw
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Edgar Tello
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Ali R. Ali
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Kun Yun
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Yanlong Pei
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Sylvia P. Thomas
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Amira D. Rghei
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Matthew M. Guilleman
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Kar Muthumani
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
Trevor Smith
Inovio Pharmaceuticals, San Diego, CA, USA
Sarah K. Wootton
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
Ami Patel
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA
David B. Weiner
The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA; Corresponding author
Darwyn Kobasa
Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; Corresponding author
Summary: 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 105 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.
