|Budget Amount *help
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1998 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Oral poliomielitis vaccine is one of the safest and most effective vaccines used in humans, as showen by the successful eradiation of paralytic cases caused by wild virulent viruse in many developed countries, but there is not the other evaluated system than the using monkey model, because of the most poliovirus are species specific. And a monkey model, however, has inherent disadavantages as follows : (1) difficulty in handling, (2) high cost of breeeding, (3) high risk of zoonosis, (4) endangered status of monkeys in natural environments.
We study that the effect of oral live poliovaccine using the transgenic mouse carrying human poliovirus receptor gene (PVR-Tg21). The MN341 derived from virulent Mohoney strain of poliovirus type 1 (MN341) and the attenuated Sabin 1 strain of poliovirus type 1 were used in this study. The PVR-Tg21 mice, orally immunized with the attenuated Sabin 1 strain of poliovirus type 1, were linoculated with MN341. (1) All non-immunized PVR-Tg mice were dead at
7dasys after the inoculation of MN341 but all immunized PVR-Tg21 mice were escaped from the death. (2) In the feces and serum of PVR-Tg2l mice with the oral- mmunization of atteneated Sabin I strain, we detected the poliovirus specific IgA and neutralization antibogy. (4) In the same PVR-Tg21 mice, the titer of poliovirus was not recognized in feces and serum. (5) The cell numberof Tlymphocytes in Peyers' pathes and tntraepithelial of small intestin were decreased at the ldays after the inoculation of MN341. But the cell number was recoverd until the 10 days. (6) The considalable CD4 cells in Peyer's patches of MN341 inoculated PVR-Tg2l mice were differanciated the IL-4 producing cells. These results indicated that the symptons of PVR-1g21 mice was similar to thata of poliovirus inoculated primates. ft is become a new animal model for study of poliovirus infection. Thus, the transgenic mice, PVR-Tg2l, may become a new animal mpdel in place of monkeys for safety testing of oral poliovirus vaccine preparations. Less