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Evaluation of Neonatal Sprague-Dawley Rats as a Potential Animal Model for the Neurovirulence Test of an Iranian
Shahkarami Mohammad Kazem1, Taqavian Mohammad1, Hablolvarid Mohammad Hasan2
1Department of Human Viral Vaccines, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
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.
Insights
This study shows neonatal Sprague-Dawley rats can effectively test mumps virus (MuV) vaccine neurovirulence. The model distinguishes between wild-type and attenuated RS-12 strains, offering a potential alternative to current safety assessments.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Mumps virus (MuV) is a neurotropic paramyxovirus causing mumps disease.
- Live-attenuated vaccines have reduced mumps outbreaks since the 1960s.
- Existing monkey-based neurovirulence tests may not accurately reflect vaccine safety in humans.
Purpose of the Study:
- To evaluate the suitability of neonatal Sprague-Dawley rats for MuV neurovirulence testing.
- To assess an Iranian MuV vaccine strain (RS-12) using this model.
- To compare the neurovirulence of attenuated and wild-type RS-12 strains.
Main Methods:
- One-day-old Sprague-Dawley rats were intracranially injected with control supernatant, RS-12 attenuated strain, or RS-12 wild-type strain.
- Animals were monitored for 30 days for weight gain, brain viral titers, and hydrocephalus.
- Brain sections were analyzed microscopically for hydrocephalus development.
Main Results:
- Weight gain was highest in controls and lowest in the wild-type group, with significant differences observed.
- Viral titers decreased over time in both vaccine and wild-type groups.
- Hydrocephalus developed in rats injected with RS-12 strains, with greater severity in the wild-type group (10%) compared to the attenuated strain (5%) and controls (1%).
Conclusions:
- Neonatal Sprague-Dawley rats can model MuV neurovirulence.
- This model can differentiate between wild-type and attenuated MuV strains.
- Further validation is needed to optimize this novel safety testing procedure.
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