Predicting the Neurovirulence Potential of Viral Vaccines for the Human CNS: The Use of Mumps Virus for Model Development
S. A. Rubin, P. Snoy and K. Carbone
Development of an in vivo system for evaluating viral neurovirulence would be of enormous benefit in vaccine development as well as in the study of host-specific mechanisms involved in virus-induced nervous system disease. Here, mumps virus strains representing a wide range of neurovirulence in humans was used for the development of a model of viral neurovirulence using neonatal rats, a host shown to be highly sensitive to perturbations by perinatal virus infection. The relative neurovirulence of each mumps virus strain was assessed based upon histological examination of the brains for neuroanatomical abnormalities. Results demonstrated that the presence and severity of hydrocephalus was proportional to the severity of the strain's known neurovirulence in humans. In addition, significant cerebellar developmental brain damage was noted in virus strains considered highly neurovirulent. If these findings can be reliably obtained in independent testing in other laboratories, there would be compelling evidence for the replacement of the poorly predictive monkey neurovirulence safety test for mumps virus vaccines with the more predictive neonatal rat model. Further, the neonatal rat model will be of great utility in elucidating the molecular pathogenesis of neurovirulence by mumps and other viruses.