Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19
Cheng‐Pu Sun, Jia‐Tsrong Jan, I-Hsuan Wang, Hsiu‐Hua Ma, Hui‐Ying Ko, Ping‐Yi Wu, Tzu-Jiun Kuo, Hsin-Ni Liao, Yu-Hua Lan, Zong‐Lin Sie, Yen‐Hui Chen, Yi-An Ko, Chun‐Che Liao, Liang-Yu Chen, I‐Jung Lee, Szu-I Tsung, Yun‐Ju Lai, Ming‐Tsai Chiang, Jian‐Jong Liang, Wen‐Chun Liu, Jing‐Rong Wang, Joyce Pei‐Yi Yuan, Yin-Shiou Lin, Yin-Shiou Lin, Yi-Ching Tsai, Shie‐Liang Hsieh, Chia-Wei Li, Han‐Chung Wu, Tai‐Ming Ko, Yi-Ling Lin, Yi-Ling Lin, Mi‐Hua Tao
Abstract
Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.