2019 Fiscal Year Final Research Report
Development of a novel T cell-oriented vaccine using CTL/Th-bi-epitope long peptide and biodegradable microparticles, against an intracellular bacterium
| Project/Area Number |
17K09650
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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 |
Respiratory organ internal medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
須田 隆文 浜松医科大学, 医学部, 教授 (30291397)
永田 年 浜松医科大学, 医学部, 教授 (90275024)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 生分解性ナノ粒子 / バイエピトープ長鎖ペプチド / 細胞内寄生菌 |
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| Outline of Final Research Achievements |
The median diameter of poly (lactic-co-glycolic acid) (PLGA) spheres was 1.38 μm. PLGA particles were taken up into 48.8% of mouse bone marrow-derived dendritic cells (BMDCs) after two-day coincubation and found mainly in endosome and lysosome by fluorescent microscopy. Both L. monocytogenes listeriolysin O (LLO)- and OVA-CTL/Th-bi-epitope long peptide (long peptide)/PLGA showed significantly more robust antigen-specific CTL and Th proliferations with higher interferon-γ production than the long peptide alone or CTL and Th short peptides/PLGA vaccination. Furthermore, the LLO-long peptide/PLGA vaccination showed significantly lower bacterial burden in spleens compared with the long peptide alone or the CTL and Th short peptides/PLGA vaccination after the challenge of lethal amounts of L. monocytogenes. These results suggest that the novel vaccine taking advantages of CTL/Th-bi-epitope long peptide and PLGA microparticle is effective for protection against intracellular bacteria.
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| Free Research Field |
細胞性免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
生分解性ナノ粒子（polylactic coglycolic acid: PLGA）を用いて抗原ペプチドをコートすることにより、生体内でのペプチドの分解を抑制し、ワクチンとして必要な高価なペプチド量を減量することが可能である。また、リンパ球への効率的な抗原提示にも寄与する。さらに、ワクチン効果の発現には細胞障害性T細胞(CTL) とヘルパーT細胞(Th)の両者の協調が必要であるが、両者のエピトープを連結したバイエピトープ長鎖ペプチドをPLGAによりコートするため、効率的に抗原特異的なCTLとThを誘導可能となる。細胞内寄生菌に対する有望な新規ワクチン療法となり得ると考えられる。
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