Establishment of mouse model for bovine coronavirus infection to accelerate development of live vaccines

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15661
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Gifu University
• Principal Investigator: Nakagawa Keisuke 岐阜大学, 応用生物科学部, 准教授 (90853250)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 牛コロナウイルス / マウスモデル

Outline of Final Research Achievements

Bovine coronavirus (BCoV) causes respiratory and diarrheal symptoms in cattle. Since there is no small animal models that reproduces the pathogenesis, it is difficult to understand the mechanism of the pathogenicity and establish candidates of attenuated live vaccine. In this study, we aimed to 1) establish a mouse model of the BCoV infection and 2) develop and evaluate attenuated vaccine candidate strain. By using the isolate of BCoV strain, we orally administered BCoV to two-day-old suckling mice. As a result, we found that two out of 10 mice showed diarrhea. We then attempted to detect infectious virus and viral genes from the diarrhea of the infected suckling mice. However, no infectious virus or viral genes were detected from the diarrhea. Furthermore, we could not find neutralizing antibodies in the suckling mice. We obtained a 20th passage of BCoV in HRT-18 cells, and are currently determining the growth property and complete genome sequence of the passage strain.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

牛コロナウイルス（BCoV）は牛に呼吸器症と下痢症を引き起こす。牛以外に本感染症の病態を再現する動物モデルが存在しないため、病態解析や弱毒生ワクチン株の樹立が進んでいない。また、マウスのゲノム編集技術を用いて病態再現マウスを樹立するのではなく、日本で販売されているコンベンショナルマウスを用いてBCoV病態再現マウスを確立できたのなら、汎用性と経済性の面で大きな利点が期待される。残念ながら本研究では、BCoV病態再現マウスの樹立は叶わなかったものの、培養細胞にて長期継代したBCoVを得ることができた。今後、継代株の増殖性を解析することで、将来的なBCoVワクチン開発に貢献できる可能性がある。