| Project/Area Number |
15K10740
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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 |
Obstetrics and gynecology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Mori Seiichiro 国立感染症研究所, 病原体ゲノム解析研究センター, 主任研究官 (80342898)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HPVワクチン / 受動免疫ワクチン / 広域中和抗体 / AAVベクター / キメラ抗体 / 交叉性中和抗体 |
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| Outline of Final Research Achievements |
At least 15 oncogenic types of human papillomavirus (HPV) cause cervical cancer. The licensed HPV vaccines consist of the major capsid protein L1 of two oncogenic HPV types and elicit type-specific neutralizing antibodies. We have previously isolated a monoclonal antibody, MAb24B, that recognizes the minor capsid protein L2. MAb24B is capable of neutralizing at least eight oncogenic HPVs in vitro. In this study, we examined the feasibility of a passive immunization vaccine using this broadly neutralizing antibody by employing adeno-associated virus (AAV)-mediated gene transfer. A single intramuscular injection of the AAV vector expressing MAb24B into mice resulted in persistent expression of MAb24B in the sera over one year. The vector-injected mice were partially protected from vaginal challenges with HPV16, HPV18, and HPV58 pseudovirions. These results provide a foundation for the development of passive immunization vaccines for a broad-spectrum of HPVs.
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| Academic Significance and Societal Importance of the Research Achievements |
全ての発癌性HPVに有効なワクチンが求められているが、そのためには15種類のL1抗原を混ぜる必要があり、技術的、コスト的な問題が指摘されている。本研究では発想を転換し、広域中和抗体を体内で発現させることで幅広い型の発癌性HPVの感染を防ぐ受動免疫ワクチンの可能性を調べた。AAVベクターを用いた遺伝子導入によりマウス体内で広域中和抗体が持続発現し、ベクター接種から1年以上経過した時点でも、複数の発癌性HPVに対する感染防御効果が認められた。これらの結果は、広域中和抗体を発現するAAVベクターが幅広い型のHPV感染を防ぐ受動免疫ワクチンとなり得ることを示すとともに開発のための基盤となる。
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