| Project/Area Number |
18K19436
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
HIGASHI Hideaki 北海道大学, 人獣共通感染症国際共同研究所, 教授 (20311227)
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| Project Period (FY) |
2018-06-29 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | タンパク質分子立体構造 / 人工分子 / 炭疽 / ワクチン抗原 / 細菌感染 / 人工抗原 / 感染予防 |
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| Outline of Final Research Achievements |
To develop a novel human anthrax vaccine, we designed a vaccine antigen molecule by in silico molecular calculation based on the multimeric structure of anthrax toxin PA. The molecule was produced in E. coli as a recombinant protein and highly purified. The multimerized molecule was generated by dimerization of the purified molecule in vitro, and was used for the mouse immunization test. The analysis of immunized mouse sera, the molecule posseted antigenicity that is almost equivalent to that of full-length PA. Furthermore the produced antibodies showed toxin-neutralizing activity. Although the immunogenicity was not significantly different from that of full-length PA, it was inferred that the molecule, in which the cell membrane-binding region involved in PA toxicity expression was deleted, and could solve the toxicity problem of the current PA vaccine.
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| Academic Significance and Societal Importance of the Research Achievements |
炭疽の予防法として、無莢膜弱毒炭疽菌が動物用炭疽生ワクチンとして世界で広く利用されている。このワクチンは、動物で炭疽予防に一定の効果を示す一方、ヒトでは重篤な副作用を示す。一部の国では、炭疽菌毒素の一つPAを利用した無細胞炭疽ワクチンをヒトに使用しているが毒性を有することから実用性に乏しい。本研究で作出した、新たな炭疽ワクチン抗原候補分子は、PAの部分構造を利用したものであり、その抗原性は従来の全長PAと同等であり、かつ産生された抗体は従来の抗原に比べ同等以上の毒素中和活性を示した。これらの事から、これまで困難とされていたヒト用炭疽ワクチン開発に関する重要な情報を示せたと考える。
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