Antigenic drift originating from changes to the lateral surface of the neuraminidase head of influenza A virus.
| Project/Area Number |
18K07141
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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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| Review Section |
Basic Section 49060:Virology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yamayoshi Seiya 東京大学, 医科学研究所, 特任准教授 (50529534)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | インフルエンザウイルス / NA蛋白質 / 抗原性 / ヒトモノクローナル抗体 / 抗体 / ADCC活性 / 抗原性変化 / NA / ヒト / ADCC / ヒト抗体 |
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| Outline of Final Research Achievements |
The reason for accumulation of amino acid substitutions at the lateral surface of the NA head remains unknown. Here, we isolated anti-NA monoclonal antibodies (mAbs) from individuals infected with A(H1N1)pdm09 virus. We found that amino acid mutations on the lateral surface of the NA head abolished the binding of these mAbs. These mAbs activated Fcγ receptor (FcγR)-mediated signaling pathways in effector cells and protected mice from lethal challenge infection via their FcγR-mediated antiviral activity. Serological analysis of individuals who were infected with A(H1N1)pdm09 virus revealed that some possessed or acquired the anti-NA lateral surface antibodies upon infection. We also found antigenic drift on the lateral surface of the NA head between 2009 isolates and 2015 isolates.
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| Academic Significance and Societal Importance of the Research Achievements |
NA蛋白質の側面領域を認識し、ウイルスのシアリダーゼ活性を阻害しない抗体も免疫細胞を活性化することで生体におけるウイルス増殖を抑制し、感染防御に寄与することが明らかになった。また、NA蛋白質側面のアミノ酸変異の蓄積が感染防御活性を持つ抗体の選択圧により引き起こされていることを示した。これにより、今後のワクチン株の選定の際、HA蛋白質の抗原性のみでなく、NA蛋白質の抗原性についても考慮することで、より効果の高いワクチン株の選定に資すると考える。
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Report
(4 results)
Research Products
(17 results)
