2019 Fiscal Year Final Research Report
Molecular machanism of varicella-zoster vaccine virus attenuation
| Project/Area Number |
17K08858
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 水痘帯状疱疹ウイルス / 弱毒生ワクチン / 弱毒化機構 |
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| Outline of Final Research Achievements |
The attenuation mechanism of a live attenuated vaccine of varicella-zoster virus (VZV) has been postulated to be stemmed from its heterogenetic nature acquired through semi-permissive cultivations. However, there has been no conclusive result regarding the attenuation mechanism. The key for uncovering the attenuation mechanism of vaccine virus should be the understanding of the population diversity of the parental VZV.
Deep sequencing analysis identified that parental VZV consists of a heterogenous population of virus sequences with two nearly equally represented bases, G or A, at nucleotide 2096 of ORF31 gene encoding the glycoprotein B (gB, the former (G) was completely absent in the vaccine virus. Strikingly, when the parental viruses with both alleles equally represented were used to infect human neurons, the virus with ORF31 nucleotide 2096G was dominant for virus entry. These data identify a variant in gB responsible for attenuation of the vaccine virus.
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| Free Research Field |
ウイルス学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、世界中で広く使用されているにもかかわらず謎の多かった、水ぼうそう・帯状疱疹ワクチンの弱毒化機構を一塩基レベルで明らかにした。水痘帯状疱疹ウイルスは多くのウイルス感染症の中でもとりわけ感染力の高いウイルスであるが、このワクチンの効果により水ぼうそうの発症は劇的に抑えられる。しかし時としてこのワクチンウイルスによる病気の発症も報告されており、弱毒化機構を理解した上でのより安全で効果的なワクチン作製が、接種率の向上による本感染症の撲滅につながると期待される。本研究成果により新たな戦略的ワクチン創出への第一歩となる知見が得られた。
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