Author: Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.
Title: A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant Document date: 2014_3_25
ID: y4zoyqua_17
Snippet: Subgroup 2c N-based vaccines and immune pathology. Previous studies from our group and others have revealed immune-mediated pathology in the lungs of mice immunized with N protein-based subunit vaccines or doubly inactivated SARS-CoV vaccines and subsequently challenged with homologous or heterologous viruses (15, 27, 28) . This immune-mediated pathology, as also noted with inactivated measles and respiratory syncytial virus (RSV) vaccines, was c.....
Document: Subgroup 2c N-based vaccines and immune pathology. Previous studies from our group and others have revealed immune-mediated pathology in the lungs of mice immunized with N protein-based subunit vaccines or doubly inactivated SARS-CoV vaccines and subsequently challenged with homologous or heterologous viruses (15, 27, 28) . This immune-mediated pathology, as also noted with inactivated measles and respiratory syncytial virus (RSV) vaccines, was characterized by the presence of high numbers of pulmonary eosinophils after challenge and potentially poses a significant barrier in the development of vaccines against other emerging CoV infections (29, 30) . Importantly, the BtCoV HKU5 N protein is 67% identical to MERS-CoV N and shares cross-reactive epitopes. As MERS-CoV does not replicate in mice, the BtCoV HKU5-SE recombinant virus offers a unique heterologous challenge model for assessing whether group 2c N proteincontaining vaccines might elicit pulmonary immune pathology characterized by increased eosinophilia upon challenge.
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