A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

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.

Previous studies from our laboratory and others have indicated that animals immunized with vectored or inactivated SARS-CoV N-containing vaccines develop an immune-mediated pathology in the lungs following homologous or heterologous challenge, reminiscent of RSV vaccine-mediated immune pathologies (27, 28) . This immune pathology is characterized by high numbers of eosinophil infiltrates in the lungs postchallenge (28) . Our results demonstrate that VRP vaccines expressing MERS-CoV N did not elicit an eosinophilic immune pathology following BtCoV HKU5-SE challenge, as reported with inactivated SARS-CoV vaccines (27) . In contrast to alum, which causes a Th2-skewed immune response (27) , VRP vaccines induce a robust Th1 immune response and high neutralizing antibody titers (15, 27) . Although these studies should be interpreted with some caution, the effects of inactivated MERS-CoV and BtCoV HKU5-SE vaccines in induction of eosinophilia following challenge remain to be tested. VRP vectors have been proven successful in human clinical trials (50, 51) , and VEE virus replicates successfully in several animal species, including horses, goats, and sheep (52) . Given the high seroprevalence of MERS-CoV in camels and the potential role of camels as intermediate reservoirs for human disease (53), the VRP platform described here may be an effective MERS-CoV vaccine candidate for use in camels and other reservoir species.