2022 Fiscal Year Final Research Report
Development of preventive method for pneumococcal infection based on control of nasopharyngeal colonization
| Project/Area Number |
20K08848
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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 54030:Infectious disease medicine-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 肺炎球菌 / 鼻咽頭定着 / 感染免疫 / NKT細胞 / 線毛タンパク |
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| Outline of Final Research Achievements |
In order to elucidate the pathogenesis of pneumococcal upper respiratory tract immunity, we focused on NKT cells and pili proteins of pneumococci. We conducted nasopharyngeal colonization experiments with NKT cell KO mice, but no significant difference was observed in the number of colonized bacteria in the nasopharynx compared with wild-type mice. In addition, α-GalCer, a ligand for NKT cells, was administered, but there was no significant difference in the number of colonized bacteria in the nasopharynx between the non-administered group and the control group.
Next, we created pili-deficient strains to analyze the role of pili in mucosal adhesion, and cloned and purified the pili protein for use as a vaccine antigen.
In the future, we will immunize mice with the purified protein, measure the amount of specific antibodies, evaluate the number of nasopharyngeal colonizers in the immunized mice, and perform functional analysis of the pilus gene disruption strain.
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| Free Research Field |
感染症内科学
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| Academic Significance and Societal Importance of the Research Achievements |
肺炎球菌感染症において鼻咽頭定着は感染症発症の第一段階として極めて重要である。また無菌環境の下気道とは異なり、鼻咽頭は常在細菌叢が存在するため、粘膜免疫応答もまた異なる。本研究は、鼻咽頭免疫の詳細を解明し、新たな同定した宿主因子および細菌側因子を介して粘膜免疫を活性化することで肺炎球菌の定着を抑制し、感染症の発症そのものを制御できる点で、既存のワクチンとは異なる新規性の高い予防法であり学術的意義は高い。また表層タンパクをワクチン抗原に使用するため莢膜型に依存することのない全肺炎球菌型の予防ワクチン開発につながる可能性があり、社会的意義も高い。
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