Tekeleselassie Ayalew Woldemariam, VIDO, University of Saskatchewan

Tekeleselassie A. Woldemariam1, Pooja Choudhary1, Jocelyne Lew1, Luz Hermida2, Milan Obradovic1, Trevor Brasel2, and Darryl Falzarano 1,3 1 Vaccine and Infectious Disease Organization (VIDO), 2 Coalition for Epidemic Preparedness Innovations (CEPI) 3Department of Veterinary Microbiology, and Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan

Fighting & Responding

Continued reports of MERS-CoV-associated fatalities highlights the need for robust preclinical models for evaluation of candidate vaccines. In this study, we evaluated temporal and spatial distribution of MERS-CoV infection in human (h) DPP4 mice following challenge. Mice expressing hDPP4 were challenged with 1x102 or 1x104 TCID50 of MERS-CoV intranasally. In both challenge groups, mice were euthanized on day 3 or day 7 post challenge. In both low- and-high dose groups, higher infectious virus titers and viral RNA copy numbers were observed in lung tissue from samples collected on day 3 post-challenge. This was accompanied by intense immunohistochemical (IHC) staining for viral nucleocapsid protein indicating a robust pulmonary replication. Samples collected at the later point in both low and high dose challenge groups revealed a dramatic increase in viral titters, viral RNA copy numbers and marked increases in IHC staining in brain tissue, demonstrating progressive viral dissemination to the central nervous system. Importantly, vaccination studies we have conducted using this model suggest that it is useful for preclinical testing of MERS-CoV vaccines even though signs of disease and tissues affected differ from those observed in humans