A novel mouse AAV6 hACE2 transduction model of wild-type SARS-CoV-2 infection studied using synDNA immunogens
E. 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 M. Reeder, Kevin Liaw, Edgar Tello, Ali Ali, Kun Yun, Yanlong Pei, Sylvia P. Thomas, Amira D. Rghei, Matthew M. Guilleman, Kar Muthumani, Trevor R.F. Smith, Sarah K. Wootton, Ami Patel, David B. Weiner, Darwyn Kobasa
Abstract
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.