Respiratory Syncytial Virus: Rodent Models and Vaccine Development

Respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide. Progress toward an effective RSV vaccine has been hampered by lack of rodent models which accurately recapitulate human disease. We developed and throughout characterized two rodent models of RSV infection, the chinchilla and the cotton rat. We found the chinchilla to be a useful model of upper airway RSV infection and the cotton rat to be a useful model of both upper and lower airway RSV infection. Additionally, we found that RSV infection of the cotton rat was associated with allergic-like lung disease. This is of particular interest given the association between RSV infection during infancy and development of asthma or recurrent wheezing in later childhood. We utilized these newly characterized rodent models to evaluate an RSV vaccine that was developed in our lab based on the hypothesis that the poor IFN response to RSV infection observed in mice and humans contributed to the relatively ineffective adaptive immune response to viral infection. To test this idea, we inserted the RSV F protein gene into the genome of Newcastle disease virus (NDV), an avian paramyxovirus that is nonpathogenic in mammals but is known to induce very high IFN levels in mice. We found that our vaccine construct, NDV-F, induced robust, long-lasting adaptive immune responses and protected chinchillas and cotton rats against RSV infection. These studies significantly contribute to the field of RSV research by characterizing rodent models that can be utilized to study mechanisms of RSV pathogenesis and by advancing a promising RSV vaccine candidate toward clinical trials.