Evaluation of Neonatal Sprague-Dawley Rats as a Potential Animal Model for the Neurovirulence Test of an Iranian Mumps Vaccine Strain, RS-12.

Introduction: Mumps virus (MuV), a neurotropic member of paramyxoviridae, causes mumps disease. Since the 1960s, when the first live-attenuated vaccine against the MuV was developed, mumps outbreaks have dramatically decreased. A monkey-based neurovirulence test has been developed and has been used to assess the safety of attenuated MuV strains. However, laboratory and clinical findings have suggested that the monkey-based test may not necessarily reflect the neurovirulence behavior of the MuV when administered to the vaccinees. A neonatal rat-based MuV neurovirulence safety test has been developed and recommended by reference institutions in recent years. This test in Lewis rats was first introduced in 1998. This study aimed to evaluate the suitability of neonatal Sprague-Dawley rats for the neurovirulence test of an Iranian MuV vaccine strain, RS-12. Materials & Methods: One-day-old Sprague-Dawley newborn rats were intracranially injected with MRC-5 cell supernatant (assigned as "C" for the control group), the RS-12 attenuated strain (assigned as "V" for the vaccine group), and the RS-12 wild-type strain (assigned as "W" for the wild-type group), respectively. The animals were observed for 30 days post-injection with regard to weight gain, viral titer in the brain tissue, and appearance of hydrocephalus in the brain sections. Results: The mean weight gain in groups C and W was the highest and lowest respectively. Regression analysis of log-transformed weight values revealed a significant difference between group C and group W. A significant difference between group V and group W was seen. There was no significant difference between the weight gain of group C and group V. No MuVs were detected in the homogenized brain samples of group C, and in groups V and W, the viral titers showed a continuous decrease during the observation period. In the microscopic view of brain sections, the hydrocephalus started to form on day 15 post-injection and reached its highest extent on day 30. On day 30 post-injection, the hydrocephalus area was determined as a maximum of 1%, 5%, and 10% for the C, V, and W groups, respectively. Conclusion: This study has introduced the newborn Sprague-Dawley rat model, capable of demonstrating the neurovirulence potential of MuV in vaccines and distinguishing between wild-type and attenuated RS-12 strains. Further experiments are needed for the optimization and validation of the test procedures.