Development of new quality control method for oral live vaccine using transgenic mice susceptible to poliovirus.

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Transgenic mice (Tg mice) carrying the human poliovirus receptor gene were susceptible to poliovirus infection showing paralysis of extremities. The pathological findings of paralytic mice were quite similar to the neuropathological changes in humans died of poliomyelitis. In this study, neuropathological changes in Tg mice inoculated with virulent strain, vaccine and field-isolates were compared to the conventional neurovirulence test using monkeys whether Tg mice are useful instead of monkeys for neurovirulence test of poliovirus vaccine.(1) Neurovirulence was observed parallel to the virus titer.(2) Intra-spinal cord administration route was established.(3) Intracerebral in oculation of field-isolates resulted in clear histopathological changes (inflammatory cell infiltration, degeneration of neurones, especially atrophy) with viral antigen in paralytic Tg mice. But in Tg mice without clinical signs no pathological changes were revealed.(4) Lesion score in monkeys was compared in Tg 21 mice by PD50 method using poliovirus type 1 and 3, and high correlation was observed reproductively and this measurement system is more precise than conventional monkey system.(5) In neurovirulence test of Tg 21 mice, high correlation was seen between in vitro poliovirus marker test and rct marker in monkeys.(6) The above results in Tg 21 mice reflects more objectively than in test using monkeys from the points of neurovirulence.(7) Stable supplying system of Tg mice was established.