NEUROVIRULENCE TEST FOR ORAL LIVE POLIOVACCINES USING POLIOVIRUS-SENSITIVE TRANSGENIC MICE

The transgenic mice, ICR-PVRTg21, carrying the human poliovirus recept or gene, were intraspinally inoculated with oral poliovirus vaccine vi ruses and the viruses that had been derived from a vaccine preparation by passagings at 38 degrees. Dose-dependent incidence of paralysis wa s observed in the transgenic mice inoculated with any of the viruses u sed. All transgenic mice showing histopathological lesions in the cent ral nervous system appeared to display clinical signs that resembled t hose observed in human poliomyelitis. These suggest that relative neur ovirulence levels of individual virus preparations can be estimated by Values of 50% paralysis dose. Indeed, the parameter correlated well w ith monkey lesion scores of viruses used. Histopathological changes su ch as degeneration of neurons resemble those displayed by monkeys and were observed in the spinal cord, medulla oblongata, and pens. Thus, t he transgenic mice, ICR-PVRTg21, may become a new animal model in plac e of monkeys for safety testing of oral poliovirus vaccine preparation s. (C) 1995 Academic Press, Inc.