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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊宏志 | |
| dc.contributor.author | Chieh-Yu Liang | en |
| dc.contributor.author | 梁潔瑜 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:10:13Z | - |
| dc.date.available | 2021-03-11 | |
| dc.date.copyright | 2019-03-11 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-11-21 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71799 | - |
| dc.description.abstract | 流感病毒造成之區域性與全球性大流行至今仍為重要的公衛議題，因此廣效型流感疫苗的發展極具必要性。源自流感病毒蛋白中高度保留區域的抗原性胜肽能夠誘發可對抗多種流感病毒亞型的T細胞免疫反應，而PLGA奈米顆粒因其安全性與致免疫性，可做為理想的疫苗攜帶物質。綜合上述，我們設計了一種由PLGA奈米顆粒同時包裹佐劑CpG與胜肽的新型疫苗，並證明此疫苗相較於沒有包裹之胜肽疫苗能達到更好的專一性T細胞免疫反應，並降低全身性副作用。我們也探討了疫苗接種成效之決定因子，包含佐劑的使用以及周邊初打-局部加打 (peripheral priming – local boosting)策略的必要性。本研究指出，以周邊初打-局部加打的策略接種同時包裹佐劑與胜肽之PLGA奈米疫苗，能建立較多的循環型記憶性T細胞以及適量的肺常駐型記憶性T細胞，而更有效地對抗流感病毒感染。進一步探討該疫苗之作用機制，結果顯示PLGA奈米顆粒能被肺部中的肺泡巨噬細胞與樹突細胞內吞。總結本篇研究，一種新型的PLGA胜肽疫苗能於疫苗接種後被抗原呈現細胞吞噬，使其於作用階段與記憶階段建立有效的專一性T細胞免疫反應，因而能於宿主受到呼吸道病毒感染時達到較佳的保護效果。 | zh_TW |
| dc.description.abstract | Influenza epidemics and pandemics remain a major health problem nowadays, necessitating the development of universal influenza vaccines. Antigenic peptides derived from the conserved regions of viral proteins are candidates for eliciting T cell responses against a broad spectrum of influenza viruses. PLGA nanoparticles have been shown to be an ideal vaccine carrier for their safety and immunogenicity. Here, we demonstrated that a novel P(O+C) vaccine, a peptide-based vaccine co-encapsulated with the adjuvant CpG by the PLGA nanoparticle, achieved enhanced specific T cell immunity and minimal systemic adverse effects as compared with soluble peptide vaccines. Several determining factors regarding the vaccination were also investigated, including the presence of adjuvants, and the necessity of “peripheral priming – local boosting” strategy. We showed that the P(O+C) vaccine with the peripheral priming and local boosting strategy was able to establish a higher number of circulating memory T cells and intermediate amount of lung resident memory T cells, and conferred more potent antiviral activity against influenza virus infection. Looking into the mechanisms of such immunopotency, we revealed that the novel PLGA vaccine is uptaken by alveolar macrophages and dendritic cells in the lung. In conclusion, our novel P(O+C) vaccine can be internalized by antigen-presenting cells to elicit robust antigen-specific T cell immunity in both the effector and the memory phase after the immunization, thereby allowing a superior protection upon respiratory virus infections. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:10:13Z (GMT). No. of bitstreams: 1 ntu-107-R05445107-1.pdf: 3852887 bytes, checksum: 0b2a1f5b888d5e7a1f3814effca4920a (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 致謝 I 摘要 II Abstract III 1. Introduction 1 1.1 Influenza Epidemics and Influenza A Virus 1 1.2 Influenza Vaccines 2 1.3 Resident Memory T Cells 3 1.4 Peptide-based Vaccines 7 1.5 Prime-boost Vaccination Strategy 9 1.6 Poly-(D,L-lactic-co-glycolic acid) Nanoparticles 10 1.7 Dendritic Cells in the Lung and Mediastinal Lymph Node 12 2. Specific Aim 14 3. Materials and Methods 15 3.1 Mice 15 3.2 Adoptive transfer 15 3.3 Viruses and infection of mice 16 3.4 Quantification of viral titers 16 3.5 PLGA nanoparticles 17 3.6 Immunization of mice 17 3.7 Measurement of OVA257-264- and OVA323-339-specific T cells 18 3.8 Intravascular staining 18 3.9 Dendritic cell isolation from the lung and lymph node 18 3.10 Cell staining, antibodies, and flow cytometry 19 3.11 Histopathology 20 3.12 Statistical analyses 20 4. Results 21 4.1 Subcutaneous P(O+C) vaccination induces effective T cell responses with minimal adverse effects 21 4.2 Intranasal P(O+C) vaccination induces effective T cell responses with mild adverse effects 24 4.3 Intranasal boosting by a proper dose of P(O+C) confers protection against IAV infection 25 4.4 Peripheral-prime/local-boost P(O+C) vaccination enables an optimal clinical outcome upon IAV infection 27 4.5 Peripheral-prime/local-boost P(O+C) vaccination mediates optimal viral clearance upon IAV infection 28 4.6 Peripheral-prime/local-boost P(O+C) vaccination generates superior circulatory memory T cell populations 30 4.7 Alveolar macrophages and dendritic cells internalize PLGA nanoparticles. 31 5. Discussion 35 5.1 Brief summary of our findings 35 5.2 Unique advantage of our PLGA nanoparticles: the small size 35 5.3 Other advantages of our model: co-encapsulation of contents 36 5.4 Limitations of our system: transferred CD4+ T cells do not last 38 5.5 Further analyses required to determine lung pathology 38 5.6 Solving systemic side effects: aerosol administration? 39 5.7 Contributions of distinctive memory T cell populations to the protection against IAV infections remain unclear 40 5.8 Implications for future vaccines: intranasal priming not necessary 41 5.9 Developing a better vaccine 41 5.10 Conclusion 42 Figures 44 Supplementary Figures 61 References 63 | |
| dc.language.iso | en | |
| dc.title | 新型PLGA胜肽疫苗提供有效對抗A型流感病毒感染之T細胞免疫力 | zh_TW |
| dc.title | A Novel PLGA-encapsulated Peptide Vaccine Confers Robust Protective T-Cell Immunity against Influenza A Virus Infections | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 朱清良,胡哲銘,陳慧文,顧家綺 | |
| dc.subject.keyword | 胜?疫苗,PLGA奈米顆粒,T細胞免疫,樹突細胞,流感病毒, | zh_TW |
| dc.subject.keyword | peptide-based vaccine,PLGA nanoparticle,T cell immunity,dendritic cells,influenza virus, | en |
| dc.relation.page | 66 | |
| dc.identifier.doi | 10.6342/NTU201804291 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-11-22 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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