| Project/Area Number |
03670240
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Health |
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Principal Investigator |
KOJIMA Asato Dept. Pathol., NIH Chief, 感染病理部, 室長 (30100077)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Tetsutaro AIDS Res. Center, NIH Chief, エイズ研究センター, 室長 (00162397)
KURATA Takeshi Dept. Pathol., NIH Director, 感染病理部, 部長 (50012779)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Recombinant Vaccinia Virus / Neurovirulence / Pathogenesis / Virus Insection / Safety / Monkey |
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| Research Abstract |
In order to evaluate the safety of recombinant vaccinia virus(RVV) as a potent live vaccine, RVVs expressing hepatitis B virus surface antigen, Japanese encephalitis virus E protein or HIV-1 gag/pol proteins were tested for the virulence in mice, guinea pigs and rabbits, and for laboratory attenuation markers in in vitro cultures. RVVs were constructed from the virulent WR strain, the Lister(Elstree) vaccine strain(LO) and the low neurovirulent LC16mO strain (mO) of vaccinia virus. Experimental animals and primary cultures of rabbit kidney cells inoculated with RVVs derived from WR, LO and mO showed the decreasing neurovirulence and skin lesions, and the increasing in vitro attenuation markers, respectively, in this order. RVVs reserved almost the same or low degree of virulence as parental wild-type trains. Virus antigens of the least virulent RVV-mO was localized only at the injection sites of the skin in intradermally inoculated animals. Even when inoculated intravenously or intraperitoneally, RVV-mO was not detected in the brain.
Based on results of the virulence tests in experimental animals, safety tests of RVV-mO were done using cynomolgus monkeys. The monkeys inoculated subcutaneously or intravenously showed neither clinical signs such as paralysis of the legs nor weight loss. No virus was recovered from the brain. Intra-cerebral inoculation of RVV-mO induced no clinical signs in monkeys during the observation period of 7 days. Histopathological examination of the monkey brain specimen showed diffuse infiltration of mononuclear cells in the meninges and mild cellular cuffing in the parenchyma. Small amounts of the RVV-mO antigens and viral genome DNA were localized at the lesions by immunoflucence and in situ hybridization analyses.
These results indicate low neurovirulence of RVV constructed from the mO strain of vaccinia virus, suggesting safety as a recombinant live vaccine for humans.
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