1996 Fiscal Year Final Research Report Summary
Development of Pharmacokinetic and Safety Assessment of in vivo Virus Infection and Vaccine Therapy
| Project/Area Number |
07557174
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tohoku University (1996)
The University of Tokyo (1995) |
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Principal Investigator |
TERASAKI Tetsuya Tohoku University, Department of Pharmacertics, Professor., 薬学部, 教授 (60155463)
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| Co-Investigator(Kenkyū-buntansha) |
SASAHARO Kunihiro Sankyou Co., Ltd., Product Development Laboratories, Group Director., 第1生産技術研究所, 所次長兼試験研究第2
TAKIGAWA Hajime Teikyo University, Department of Internal Medicine, Associate Professor., 医学部, 助教授 (70197226)
AOKI Junken University of Tokyo, Department of Pharmaceutic, Research Associate., 薬学部, 助手 (20250219)
KATO Yukio University of Tokyo, Department of Pharmaceutic, Research Associate., 薬学部, 助手 (30251440)
SUGIYAMA Yuichi University of Tokyo, Department of Pharmaceutic, Professor., 薬学部, 教授 (80090471)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Poliovirus / Virus receptor / Pharmacokinetics / Vaccine / Brain / Organ tropism / Blood-brain barrier : / Transgenic mouse |
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| Research Abstract |
It is significantly important subjict to elucidate the mechanism of organ tropism of virus infection in gene and vaccine therapy. In the present study, poliovirus, known to be the causative agent of poliomyelitis, has been selected as a model virus to develop the safety assesement of vaccine therapy and to predict the in vivo virus infection in the body based on pharmacokinetic analysis. The transgenic (Tg) mice carrying the human gene for poliovirus receptor (PVR), which is susceptible to intraven ously (IV) -inoculated poliovirus, has been used for the in vivo enfection studies. To know cotribution of PVR to tissue distribution and BBB permeability of IV-inoculated polioviruses, these processes were investigated and compared between the Tg mice and non-Tg mice. Distribution profile of IV-inoculated poliovirus in various tissues of the Tg mice is similar to that in non-Tg mice, suggesting that tissue distribution of IV-inoculated virus is independent of the transgene for PVR.Amount of poliovirus transfered to the CNS demonstrates an existence of specific invasion pathway for the virus to the CNS.The viruses, regardless of whether the virulent and attenuated strain, seem to accumulate at a constant rate of approximately 0.2ul/min/g brain. Similar phenomena were observed when the viruses were inoculated into non-Tg mice. These data suggest that polioviruses permeate the BBB at a fairly high rate, independently of PVR and verus strains. If it is also true in humans, circulating poliovirus including the Sabin vaccine strains easily invade the human CNS.Some molecules other than PVR may be involved in the BBB permeability of poliovirus.
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