Congenital brain damage due to intrauterine virus infections is a significant pediatric problem. In addition, the brain continues to develop during the first year of postnatal life. Since the developing nervous system is uniquely sensitive to damage following virus infection, administering neurovirulent vaccines to infants can place the child~s nervous system at increased risk for vaccine related injury. Mumps virus, and certain strains of mumps vaccine (Urabe Am9, Leningrad 3), are among the most neurotropic of the early childhood viruses, and new MMR combinations continue to be proposed, including new strains of mumps vaccine virus. Neurovirulence safety tests (NVST) are needed to identify neurovirulent vaccines that may cause CNS disease following vaccination. Progress: NSVT Development: Primate: Developed and tested a simplified, biologically relevant, standardized primate NVST. Animals inoculated with wild type and vaccine strains of mumps virus developed inflammation. Licensed mumps vaccine was statistically no different from experimental mumps vaccine. The test was unable to differentiate vaccine from wild type strains at a single dose; thus additional studies are underway to evaluate the """"""""dose response"""""""" curve for each virus re: ability to induce neurological damage. In addition, we are developing, testing and validating virus and immune serum standards for assistance in uniform execution of primate NVST by regulatory agencies and sponsors. Small animal: A newborn rat NVST was developed and tested with neurovirulent (Kilham) and relatively non-neurovirulent (Jeryl-Lynn) strains of mumps viruses. Using physiological, neuroanatomical and behavioral endpoints, significant differences were identified in rats infected at birth with Kilham or Jeryl-Lynn viruses. These results are In Press in J. Virology, 1998. Additional experiments are underway to complete validation of this model system and to evaluate a dose-response curve for neurovirulence induction by wild type and vaccine mumps virus strains.
