A novel mouse AAV6 hACE2 transduction model of wild-type SARS-CoV-2 infection studied using synDNA immunogens.
| Autor: | Gary EN; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Warner BM; Public Health Agency of Canada, Winnipeg, MB, Canada., Parzych EM; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Griffin BD; Public Health Agency of Canada, Winnipeg, MB, Canada., Zhu X; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Tailor N; Public Health Agency of Canada, Winnipeg, MB, Canada., Tursi NJ; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Chan M; Public Health Agency of Canada, Winnipeg, MB, Canada., Purwar M; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Vendramelli R; Public Health Agency of Canada, Winnipeg, MB, Canada., Choi J; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Frost KL; Public Health Agency of Canada, Winnipeg, MB, Canada., Reeder S; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Liaw K; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Tello E; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Ali AR; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Yun K; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Pei Y; Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Thomas SP; Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Rghei AD; Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Guilleman MM; Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Muthumani K; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Smith T; Inovio Pharmaceuticals, San Diego, CA, USA., Wootton SK; Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Patel A; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Weiner DB; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Kobasa D; Public Health Agency of Canada, Winnipeg, MB, Canada.; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2021 Jul 23; Vol. 24 (7), pp. 102699. Date of Electronic Publication: 2021 Jun 08. |
| DOI: | 10.1016/j.isci.2021.102699 |
| Abstrakt: | 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 TCID Competing Interests: D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. Remuneration received by D.B.W. includes direct payments, stock or stock options, and in the interest of disclosure D.B.W. discloses the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Advisory Board, Speaker), Inovio (BOD, SRA, Stock), Sanofi (Advisory Board), BBI (Advisory Board). (© 2021 The Author(s).) |
| Databáze: | MEDLINE |
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