Development of a screening system of novel antigenic variants using a low-fidelity polymerase-based influenza virus strain.
Project/Area Number |
17K09170
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hygiene and public health
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Research Institution | Kawasaki Medical School |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | インフルエンザウイルス / ワクチン開発 / 抗原変異 / ウイルスポリメラーゼ / 遺伝子変異 / 免疫逃避 / ウイルスライブラリー / ウイルス進化 / ウィルス / 感染症 / 免疫学 / 衛生 |
Outline of Final Research Achievements |
Influenza A virus rapidly acquires antigenic changes, which limit the effectiveness of vaccines, primarily owing to its high rate of evolution. To predict the antigenic properties of future epidemic strains of human influenza A virus, we attempted to develop the screening system of novel antigenic variants using a mutator polymerase-based influenza virus strain. An important advantage of our method for isolation of an escape variant is that we can screen those viruses using the mutant virus library derived from own low-fidelity polymerase that do not require random mutagenesis by targeting PCR. In this study, we demonstrated that antigenic escape variants could be isolated from mutant virus libraries with random mutations introduced by RNA genome-wide mutagenesis system for the whole influenza viral gene. This approach would enable the selection of future vaccine candidates before antigenic mutant viruses emerge in nature.
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Academic Significance and Societal Importance of the Research Achievements |
ワクチン製造株の選定条件として、①ウイルス増幅時に抗原部位に変異が導入されず、②ウイルスが高増殖性であり、③ウイルス抗原蛋白質(ヘマグルチニン)が高収率で精製できる必要がある。新規抗原変異株の出現後に、以上の条件を備えたウイルス株を速やかに単離して次シーズンのワクチン製造に間に合わせるのは困難である。本研究により、単離した抗原変異株のウイルス学的特徴と将来的なウイルス進化の方向性を事前に把握できれば、新規抗原変異株の出現時において迅速なワクチン開発が可能になる。さらに、その情報をもとに「未来流行株」に対するワクチン製造プロトコルを確立することが可能になる。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.2018
Author(s)
Naito T, Yasunaga JI, Mitobe Y, Shirai K, Sejima H, Ushirogawa H, Tanaka Y, Nakamura T, Hanada K, Fujii M, Matsuoka M, Saito M.
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Journal Title
Retrovirology
Volume: 15
Issue: 1
Pages: 72-72
DOI
NAID
Related Report
Peer Reviewed / Open Access
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