Development of the ferret model for EV-D68 infection

ABSTRACT Acute Flaccid Myelitis (AFM) is a debilitating condition in young children. The exact cause of AFM is currently unknown though EV-D68, an enterovirus has been temporally associated with AFM. The exact mechanism's by which EV-D68 causes spinal cord and CNS pathology is not known. Here we propose the development of an immunocompetent small animal model, namely the ferret to study EV-D68 infections. Ferrets have been widely used as a model to study respiratory pathogens such as influenza, RSV, SARS, Hendra and Nipah viruses. Given that the lower respiratory tract is the primary route of entry for EV-D68, we hypothesize that ferrets will serve as a viable model to study EV-D68 pathogenesis. In aim 1, we will develop the model of intranasal infection and delineate the correlates of pathogenesis and immunity, and in aim 2 we will develop a novel avian paramyxovirus based EV-D68 vaccine to examine its potential to prevent intranasal challenge. These studies will provide novel insights into the mechanisms of EV-D68 pathogenesis and vaccine mediated protection from respiratory infections.