請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19102
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
dc.contributor.author | Chiao-Li Chin | en |
dc.contributor.author | 秦僑莉 | zh_TW |
dc.date.accessioned | 2021-06-08T01:45:08Z | - |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-15 | |
dc.identifier.citation | 1. Blomberg, J., et al., New enterovirus type associated with epidemic of aseptic
meningitis and/or hand, foot, and mouth disease. The Lancet, 1974. 304.7872: p. 112. 2. Hagiwara, A., et al., Epidemic of hand, foot, and mouth disease asssciated with enterovirus 71 infection. Intervirology, 1978. 9: p. 60-63. 3. Alexander, J.P., et al., Enterovirus 71 infections and neurologic disease—United States, 1977–1991. Journal of Infectious Diseases, 1994. 169.4: p. 905-908. 4. Shieh, W.-J., et al., Pathologic studies of fatal cases in outbreak of hand, foot, and mouth disease, Taiwan. Emerging Infectious Diseases, 2001. 7.1: p. 146. 5. Chumakov, M., et al., Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Archives of Virology, 1979. 60.3-4: p. 329-340. 6. Ho, M., et al., An epidemic of enterovirus 71 infection in Taiwan. New England Journal of Medicine, 1999. 341.13: p. 929-935. 7. Ho, M., et al., Enterovirus 71: the virus, its infections and outbreaks. Journal of Microbiology, Immunology, and Infection, 2000. 33.4: p. 205-216. 8. Xing, W., et al., Hand, foot, and mouth disease in China, 2008–12: an epidemiological study. The Lancet Infectious Diseases, 2014. 14.4: p. 308-318. 9. Chang, L.-Y., Enterovirus 71 in Taiwan. Pediatrics & Neonatology, 2008. 49.4: p. 103-112. 10. Van Tu, P., et al., Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerging Infectious Diseases, 2007. 13.11: p. 1733-1741. 11. Wu, Y., et al., The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains. Journal of Infectious Diseases, 2010. 14.12: p. e1076-e1081. 12. Ahmad, K., Hand, foot, and mouth disease outbreak reported in Singapore. The Lancet, 2000. 356.9238: p. 1338. 13. Chua, K.B., and Abdul Rasid Kasri., Hand foot and mouth disease due to enterovirus 71 in Malaysia. Virologica Sinica 2011. 26.4: p. 221-228. 14. Tao, Z., et al., Non-polio enteroviruses from acute flaccid paralysis surveillance in Shandong Province, China, 1988–2013. Scientific Reports, 2014. 4. 15. Li, W., et al., Epidemiology of childhood enterovirus infections in Hangzhou, China. Virology Journal 2015. 12.1: p. 58. 16. Wang, S.-M., and Ching-Chuan Liu., Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine. Expert Review of Anti-infective Therapy, 2014. 12.4: p. 447-456. 17. Chen, S.-C., et al., An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan. The American Journal of Tropical Medicine and Hygiene, 2007. 77.1: p. 188-191. 18. Zhang, Y., et al., Pathogenesis study of enterovirus 71 infection in rhesus monkeys. Laboratory Investigation, 2011. 91.9: p. 1337-1350. 19. Han, J., et al., Long persistence of EV71 specific nucleotides in respiratory and feces samples of the patients with Hand-Foot-Mouth Disease after recovery. BioMed Central Infectious Diseases, 2010. 10.1: p. 178. 20. Chang, L.-Y., et al., Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan. Pediatrics, 2002. 109.6: p. e88-e88. 21. Ruan, F., et al., Risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing. Pediatrics, 2011. 127.4: p. e898-e904. 22. Chang, L.-Y., et al., Outcome of enterovirus 71 infections with or without stagebased management: 1998 to 2002. The Pediatric Infectious Disease Journal, 2004. 23.4: p. 327-332. 23. Chang, L.-Y., et al., Neurodevelopment and cognition in children after enterovirus 71 infection. New England Journal of Medicine, 2007. 356.12: p. 1226-1234. 24. De Colibus, L., et al., More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nature Structural & Molecular Biology, 2014. 21.3: p. 282-288. 25. Gao, M., et al., The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins. Antiviral Research, 2014. 106: p. 80-85. 26. Strating, J.R., et al., Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. Cell Reports, 2016. 10.4: p. 600-615. 27. Riedel, S., Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center), 2005. 18.1: p. 21. 28. Zhu, F.-C., et al., Efficacy, safety, and immunology of an inactivated alumadjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 2013. 381.9882: p. 2024-2032. 29. Hu, Y.-M., et al., Immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71 vaccine in Chinese children aged 6 to 59 months. Clinical and Vaccine Immunology, 2013. 20.12: p. 1805-1811. 30. Zhu, F., et al., Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. New England Journal of Medicine, 2014. 370.9: p. 818-828. 31. Lycke, N., Recent progress in mucosal vaccine development: potential and limitations. Nature Reviews Immunology, 2012. 12.8: p. 592-605. 32. Williams, I.R., Chemokine receptors and leukocyte trafficking in the mucosal immune system. Immunologic Research, 2004. 29.1-3: p. 283-291. 33. Gill, N., Marta Wlodarska, and B. Brett Finlay., The future of mucosal immunology: studying an integrated system-wide organ. Nature Immunology, 2010. 11.7: p. 558-560. 34. De Magistris, M.T., Mucosal delivery of vaccine antigens and its advantages in pediatrics. Advanced Drug Delivery Reviews, 2006. 58.1: p. 52-67. 35. Holmgren, J., and Cecil Czerkinsky., Mucosal immunity and vaccines. Nature Medicine, 2006. 11: p. S45-S53. 36. Kozlowski, P.A., et al., Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle. The Journal of Immunology, 2002. 169.1: p. 566-574. 37. Staats, H.F., Sean P. Montgomery, and Thomas J. Palker., Intranasal immunization is superior to vaginal, gastric, or rectal immunization for the induction of systemic and mucosal anti-HIV antibody responses. AIDS Research And Human Retroviruses, 1997. 13.11: p. 945-952. 38. Ambrose, C.S., Catherine Luke, and Kathleen Coelingh., Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza. Influenza And Other Respiratory Viruses, 2008. 2.6: p. 193-202. 39. Carter, N.J., and Monique P. Curran., Live Attenuated Influenza Vaccine (FluMist®; Fluenz™). Drugs, 2011. 71.12: p. 1591-1622. 40. Dhere, R., et al., A pandemic influenza vaccine in India: from strain to sale within 12 months. Vaccine, 2011. 29: p. A16-A21. 41. Kulkarni, P.S., et al., Effectiveness of an Indian-made Attenuated influenza A (H1N1) pdm 2009 vaccine: A case control study. Human Vaccines & Immunotherapeutics, 2014. 10.3: p. 566-571. 42. Talbot, T.R., et al., Duration of virus shedding after trivalent intranasal live attenuated influenza vaccination in adults. Infection Control, 2005. 26.05: p. 494-500. 43. Anonymous., Flu mystified: hospitals are in a fog of live viral vaccine issues. Hospital Infection Control, 2004. 31: p. 1-5. 44. Ogra, P.L., Howard Faden, and Robert C. Welliver., Vaccination strategies for mucosal immune responses. Clinical Microbiology Reviews, 2001. 14.2: p. 430- 445. 45. Lowrey, J.A., et al., Induction of tolerance via the respiratory mucosa. International Archives of Allergy and Immunology, 1998. 116.2: p. 93-102. 46. Pasquale, A.D., et al., Vaccine Adjuvants: from 1920 to 2015 and Beyond. Vaccines, 2015. 3.2: p. 320-343. 47. Glenny, A.T., and Mollie Barr., The precipitation of diphtheria toxoid by potash alum. The Journal of Pathology and Bacteriology, 1931. 34.2: p. 131-138. 48. Vogel, F.R., Michael F. Powell, and Carl R. Alving., A compendium of vaccine adjuvants and excipients. Vaccine Design: the subunit and adjuvant approach, 1995. 6: p. 141-228. 49. Hutchison, S., et al., Antigen depot is not required for alum adjuvanticity. The Federation of American Society for Experimental Biology (FASEB) Journal, 2012. 26.3: p. 1272-1279. 50. Eisenbarth, S.C., et al., Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature, 2008. 453.7198: p. 1122-1126. 51. Li, H., et al., Cutting edge: inflammasome activation by alum and alum’s adjuvant effect are mediated by NLRP3. The Journal of Immunology, 2008. 181.1: p. 17-21. 52. Pétrilli, V., et al., The inflammasome: a danger sensing complex triggering innate immunity. Current Opinion in Immunology, 2007. 19.6: p. 615-622. 53. Chen, M., et al., Regulation of adaptive immunity by the NLRP3 inflammasome. International Immunopharmacology, 2011. 11.5: p. 549-554. 54. Ulrich, J.T., and Kent R. Myers., Monophosphoryl lipid A as an adjuvant. Vaccine Design. Springer US, 1995: p. 495-524. 55. Martin, M., Suzanne M. Michalek, and Jannet Katz., Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A. Infection and Immunity, 2003. 71.5: p. 2498-2507. 56. Alpar, H.O., J. C. Bowen, and M. R. W. Brown., Effectiveness of liposomes as adjuvants of orally and nasally administered tetanus toxoid. International Journal of Pharmaceutics, 1992. 88.1: p. 335-344. 57. Brewer, J.M., et al., In interleukin‐4‐deficient mice, alum not only generates T helper 1 responses equivalent to Freund's complete adjuvant, but continues to induce T helper 2 cytokine production. European Journal of Immunology, 1996. 26.9: p. 2062-2066. 58. Boland, G., et al., Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04. Vaccine, 2004. 23.3: p. 316-320. 59. Childers, N.K., et al., Adjuvant activity of monophosphoryl lipid A for nasal and oral immunization with soluble or liposome-associated antigen. Infection and Immunity, 2000. 68.10: p. 5509-5516. 60. Rappuoli, R., et al., Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunology Today, 1999. 20.11: p. 493-500. 61. Banerjee, S., et al., Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers. Gut, 2002. 51.5: p. 634-640. 62. Peppoloni, S., et al., Mutants of the Escherichia coli heat-labile enterotoxin as safe and strong adjuvants for intranasal delivery of vaccines. Expert Review of Vaccines, 2003. 2.2: p. 285-293. 63. Lewis, D.J., et al., Transient facial nerve paralysis (Bell’s palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS One, 2009. 4.9: p. e6999. 64. Lin, Y.-L., et al., Intranasal vaccination with poly (I: C) and CpG as adjuvants enhances mucosal and systemic immune responses to an Enterovirus 71 vaccine. Journal of Microbiology, Immunology and Infection, 2015. 48.2: p. S136. 65. Weis, W.I., Maureen E. Taylor, and Kurt Drickamer., The C‐type lectin superfamily in the immune system. Immunological Reviews, 1998. 163.1: p. 19- 34. 66. Steinman, R.M., Decisions about dendritic cells: past, present, and future. Annual Review of Immunology, 2012. 30: p. 1-22. 67. Geijtenbeek, T.B., and Sonja I. Gringhuis., C-type lectin receptors in the control of T helper cell differentiation. Nature Reviews Immunology, 2016. 16.7: p. 433- 448. 68. Brown, G.D., et al., Dectin-1 is a major β-glucan receptor on macrophages. The Journal of Experimental Medicine, 2002. 196.3: p. 407-412. 69. Taylor, P.R., et al., The β-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. The Journal of Immunology, 2002. 169.7: p. 3876-3882. 70. Granucci, F., et al., Early IL-2 production by mouse dendritic cells is the result of microbial-induced priming. The Journal of Immunology, 2003. 170.10: p. 5075-5081. 71. Edwards, A.D., et al., Microbial recognition via Toll-like receptor-dependent and-independent pathways determines the cytokine response of murine dendritic cell subsets to CD40 triggering. The Journal of Immunology, 2002. 169.7: p. 3652-3660. 72. Yazdi, A.S., et al., Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β. Proceedings of the National Academy of Sciences, 2010. 107.45: p. 19449-19454. 73. Smith, A., Michael Perelman, and Michael Hinchcliffe., Chitosan: A promising safe and immune-enhancing adjuvant for intranasal vaccines. Human Vaccines & Immunotherapeutics, 2014. 10.3: p. 797-807. 74. Russell, R.F., et al., Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice. Journal of Virology, 2016. 90.9: p. 4735-4744. 75. Parasuraman, S., R. Raveendran, and R. Kesavan., Blood sample collection in small laboratory animals. Journal of Pharmacology & Pharmacotherapeutics, 2010. 1.2: p. 87. 76. Geijtenbeek, T.B., and Sonja I. Gringhuis., Signalling through C-type lectin receptors: shaping immune responses. Nature Reviews Immunology, 2009. 9.7: p. 465-479. 77. Robinson, M.J., et al., Myeloid C-type lectins in innate immunity. Nature Immunology, 2006. 7.12: p. 1258-1265. 78. Sutterwala, F.S., Stefanie Haasken, and Suzanne L. Cassel., Mechanism of NLRP3 inflammasome activation. Annals of the New York Academy of Sciences, 2014. 1319.1: p. 82-95. 79. Bauernfeind, F.G., et al., Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. The Journal of Immunology, 2009. 183.2: p. 787-791. 80. Lepenies, B., Junghoon Lee, and Sanjiv Sonkaria., Targeting C-type lectin receptors with multivalent carbohydrate ligands. Advanced Drug Delivery Reviews, 2013. 65.9: p. 1271-1281. 81. McGreal, E.P., et al., The carbohydrate-recognition domain of Dectin-2 is a Ctype lectin with specificity for high mannose. Glycobiology, 2006. 16.5: p. 422- 430. 82. Brown, G.D., Dectin-1: a signalling non-TLR pattern-recognition receptor. Nature Reviews Immunology, 2006. 6.1: p. 33-43. 83. Gantner, B.N., et al., Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. The Journal of Experimental Medicine, 2003. 197.9: p. 1107-1117. 84. Sato, M., et al., Direct binding of Toll-like receptor 2 to zymosan, and zymosaninduced NF-κB activation and TNF-α secretion are down-regulated by lung collectin surfactant protein A. The Journal of Immunology, 2003. 171.1: p. 417- 425. 85. Tan, C.W., et al., Enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor. Journal of Virology, 2013. 87.1: p. 611-620. 86. Kumar, H., et al., Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal β-glucan. The Journal of Immunology, 2009. 183.12: p. 8061-8067. 87. Kankkunen, P., et al., (1, 3)-β-Glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. The Journal of Immunology, 2010. 184.11: p. 6335-6342. 88. LeibundGut-Landmann, S., et al., Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nature Immunology, 2007. 8.6: p. 630-638. 89. LeibundGut-Landmann, S., et al., Stimulation of dendritic cells via the dectin- 1/Syk pathway allows priming of cytotoxic T-cell responses. Blood, 2008. 12.13: p. 4971-4980. 90. Lin, L., Andrea J. Gerth, and Stanford L. Peng., CpG DNA redirects classswitching towards' Th1‐like' Ig isotype production via TLR9 and MyD88. European Journal of Immunology, 2004. 34.5: p. 1483-1487. 91. Dandekar, S., Michael D. George, and Andreas J. Bäumler., Th17 cells, HIV and the gut mucosal barrier. Current Opinion in HIV and AIDS, 2010. 5.2: p. 173- 178. 92. Jaffar, Z., et al., Cutting edge: lung mucosal Th17-mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels. The Journal of Immunology, 2009. 182.8: p. 4507-4511. 93. Briere, F., et al., Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA. Journal of Clinical Investigation, 1994. 94.1: p. 97. 94. Paul, W.E., and Jinfang Zhu., How are TH2-type immune responses initiated and amplified?. Nature Reviews Immunology, 2010. 10.4: p. 225-235. 95. Binder, G.K., and Diane E. Griffin., Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons. Science, 2001. 293.5528: p. 303- 306. 96. Chen, Z., et al., IL-6, IL-10 and IL-13 are associated with pathogenesis in children with Enterovirus 71 infection. International Journal of Clinical and Experimental Medicine, 2014. 7.9: p. 2718. 97. WU, H.Y., H. H. Nguyen, and M. W. Russell., Nasal lymphoid tissue (NALT) as a mucosal immune inductive site. Scandinavian Journal of Immunology, 1997. 46.5: p. 506-513. 98. Fuentes, A.-L., Len Millis, and Lynette B. Sigola., Laminarin, a soluble betaglucan, inhibits macrophage phagocytosis of zymosan but has no effect on lipopolysaccharide mediated augmentation of phagocytosis. International Immunopharmacology, 2011. 11.1: p. 1939-1945. 99. Mansour, M. K., et al. Dectin-1 activation controls maturation of β-1, 3-glucancontaining phagosomes. Journal of Biological Chemistry, 2013. 288.22:p. 16043-16054. 100. Liu, L., et al., Neonatal rhesus monkey is a potential animal model for studying pathogenesis of EV71 infection. Virology, 2011. 412.1: p. 91-100. 101. Yamayoshi, S., Ken Fujii, and Satoshi Koike., Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases. Frontiers in Microbiology, 2012. 3. 102. Lin, Y.-W., et al., Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71. PLoS One, 2013. 8.2: p. e57591. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19102 | - |
dc.description.abstract | 黏膜疫苗的優點在於施用方便且能在感染之初有效清除病原,但容易誘
發免疫耐受性而降低其效果;施用佐劑則可以透過營造有利於黏膜免疫反應發生的環境來突破耐受性的困境,甚至刺激黏膜抗體產生。一群病原相關分子模式與損傷相關分子模式已被認為能夠藉由與模式識別受體的交互作用活化先天免疫系統,進一步促進抗原專一免疫反應的發生。在這些分子模式中,我們鎖定三個先天免疫受體配基作為試驗目標: 酵母多醣為酵母菌細胞壁多醣成分,能與先天免疫細胞表面的類鐸受體2、樹突細胞相關之鈣型凝集素受體1 作用;殼聚醣與奈米氧化矽分別為真菌細胞壁成分與人工奈米化顆粒,兩者皆能活化先天免疫細胞內的NLRP3 發炎小體。在本篇文章中,我們探討的是酵母多醣(zymosan)、殼聚醣(chitosan)與奈米氧化矽(nano-SiO2)作為黏膜佐劑之潛力。在細胞試驗中,我 們證實酵母多醣能夠有效活化骨髓分化之樹突細胞,促進間白素-10、12 p40、12 p70 的分泌;除此之外,連續以酵母多醣與殼聚醣或奈米氧化矽處理能促進骨髓分化之樹突細胞與巨噬細胞的活化,使其產生高量的間白素-1β。在動物實驗中,我們也觀察到以抗原加上酵母多醣致敏能使BALB/c 小鼠的抗原專一免疫反應增強,包含血清中的免疫球蛋白G 濃度、鼻腔沖洗液與糞便中的免疫球蛋白A濃度、抗原再刺激之脾臟細胞分裂增生的能力與間白素-17 的分泌量相較於只以抗原致敏的組別皆顯著地提升;更重要的是,血清抗體與病毒中和試驗的結果支持以抗原加上酵母多醣、殼聚醣與奈米氧化矽致敏的小鼠血清能有效提供細胞保護力避免病毒感染。除此之外,這些多醣化物與奈米顆粒在細胞試驗與動物試驗中皆顯示為低毒性。綜合以上實驗結果,我們推論酵母多醣、殼聚醣與奈米氧化矽可以作為有潛力之腸病毒七十一型黏膜佐劑。 | zh_TW |
dc.description.abstract | Mucosal vaccines benefit in convenience of application and pathogen clearance at the site of entry, but are limited in low efficiency to induce immune responses.
Administration of an adjuvant could enhance immune responses by building the cytokine environment in favor of mucosal immunity rather than tolerance and promoting mucosal antibody production. To induce these antigen –specific responses, one effective approach is to activate the innate immunity. A range of pathogen associated molecular patterns (PAMP) and damage associated molecular patterns (DAMP) have been postulated to trigger innate immune responses by interacting with pattern recognition receptors (PRR). Of our interest are three innate receptor ligands in the following. Zymosan, a glucan derived from yeasts with β-1, 3-linkage, interacts with Toll-like receptor (TLR) 2/6 heterodimer and dectin-1 on the surface of innate immune cells. Another two include chitosan, a cationic polysaccharide abundant in the cell wall of fungi, and synthetic nanoparticle of silicon dioxide (nano-SiO2). Both of them could activate NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in innate immune cells. In this study, we targeted at the potential immuno-inducibility of zymosan, chitosan and nano-SiO2 as mucosal adjuvants. At the cellular level, we showed that maturation of bone-marrow derived dendritic cells (BMDC) was promoted after treatment with zymosan by inducing IL-10, IL-12 p40 and IL-12 p70 production. Besides, activation of BMDC and bone-marrow derived macrophage (BMDM) were culminated in the induction of IL-1β secretion after sequential treatment with zymosan and chitosan/ nano-SiO2. Based on the in vitro results, we observed that BALB/c mice immunized with antigen plus zymosan exhibited elevated Enterovirus 71 (EV71)- specific immune responses, including the IgG titer in sera, the IgA titer in nasal wash and feces, the proliferation level and IL-17 production from the restimulated splenocytes increased significantly, compared with the antigen alone group. Furthermore, we confirmed minor toxicity of zymosan, chitosan and nano-SiO2 at low concentration both in vitro and in vivo. Taken together, our data suggested that zymosan, chitosan, and nano-SiO2 could be used as potential adjuvants in intranasal EV71 vaccine. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:45:08Z (GMT). No. of bitstreams: 1 ntu-105-R03449010-1.pdf: 2214451 bytes, checksum: 2379d93bcb17cf9895dcf74c144a9606 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | Verification letter from the Oral Examination Committee ................................................ i
致謝.... ......................................................................................... ii 中文摘要....................................................................................................................... iv Abstract............................................................................................................................ v Table of Contents........................................................................................................... vii List of Figures................................................................................................................. xi List of Tables ................................................................................................................. xiii I. Introduction .......................................................................................................... 1 1-1 The global epidemiology and pathogenesis of EV71............................................. 1 1-2 Current strategies in the treatment of EV71 infection............................................ 2 1-3 Developing intranasal EV71 vaccine: Advantages and challenges........................ 4 1-4 Adjuvant application: Models and their limitations ............................................... 5 1-5 The aim and the approach of the study................................................................... 7 II. Materials and Methods ....................................................................................... 10 2-1 Chemicals ............................................................................................................. 10 2-2 Mice...................................................................................................................... 10 2-3 Cell cultures.......................................................................................................... 10 2-4 Flow cytometric analyses ......................................................................................11 2-5 Gene expressions of C-type lectin receptor (CLR) in BMDC ..............................11 2-6 Treatment of BMDC with C-type lectin receptor ligands .................................... 13 2-7 Treatment of BMDM/BMDC with agonists of NLRP3 inflammasome .............. 13 2-8 Cytotoxicity assays............................................................................................... 14 2-9 Purification of EV71 ............................................................................................ 14 2-10 Intranasal immunization..................................................................................... 15 2-11 Collection of sera, nasal wash and splenocytes.................................................. 16 2-12 Determination of EV71 specific antibodies ....................................................... 17 2-13 Proliferation assay.............................................................................................. 18 2-14 Antigen-specific cytokine analyses .................................................................... 18 2-15 Quantification of cytokine productions by ELISA ............................................ 19 2-16 Neutralization assay ........................................................................................... 19 2-17 Statistical analysis .............................................................................................. 20 III. Results ................................................................................................................ 21 3-1 Study design and preparation of the cell cultures. ............................................... 21 3-2 Eight C-type lectin receptors were focused due to their highly expression in BMDC, at least in transcriptional level. ........................................................................... 22 3-3 IL-10 and IL-12 production from BMDC were significantly promoted upon treatment with zymosan...................................................................................... 22 3-4 TNF-α and IL-1β secretion from BMDM and BMDC were substantially induced upon sequential treatment with zymosan and chitosan. ..................................... 24 3-5 Treatment with zymosan and chitosan brought about minor concern of cytotoxicity. ............................................................................................................................ 25 3-6 The intranasal immunization test. ........................................................................ 26 3-7 Intranasal immunization with EV71 plus zymosan and/or chitosan as adjuvants caused a minor impact on the weight of mice. ................................................... 27 3-8 Production of EV71-specific antibodies in serum, nasal wash, and feces increased after three times of intranasal immunization with EV71 plus zymosan and chitosan as adjuvants. ......................................................................................... 27 3-9 Not only the proliferation level but also the production of IL-6 and IL-17 from the re-stimulated splenocytes were promoted after three times of intranasal immunization with EV71 plus zymosan and chitosan as adjuvants. .................. 28 3-10 The production of IL-1β was significantly induced upon sequential treatment of BMDM and BMDC with zymosan and nano-SiO2 ............................................ 30 3-11 Treatment with nano-SiO2 at low concentrations in vitro might not be seriously toxic. ................................................................................................................... 30 3-12 Intranasal immunization with EV71 plus zymosan and/or nano-SiO2 as adjuvants caused a minor impact on the weight of mice. ................................................... 31 3-13 Production of EV71-specific antibodies in serum, nasal wash, and feces elevated after three times of intranasal immunization with EV71 plus zymosan............. 31 3-14 Sera from the groups immunized with EV71 plus zymosan showed high protection efficiency in vitro. ............................................................................. 32 3-15 Production of IL-6, IL-17, IL-5, IL-10, and IL-13 from the re-stimulated splenocytes was promoted after three times of intranasal immunization with EV71 plus zymosan. ..................................................................................................... 33 IV. Discussion........................................................................................................... 35 V. References .......................................................................................................... 42 VI. Figures................................................................................................................50 VII. Tables................................................................................................................74 | |
dc.language.iso | en | |
dc.title | 研究促進腸病毒七十一型鼻黏膜疫苗免疫反應 | zh_TW |
dc.title | Study on Enhancing Immune Responses Induced by Intranasal Enterovirus 71 Vaccine | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張鑾英,顧家綺 | |
dc.subject.keyword | 黏膜疫苗,佐劑,腸病毒,酵母多醣,殼聚糖,奈米氧化矽, | zh_TW |
dc.subject.keyword | Adjuvant,Chitosan,Enterovirus 71,Intranasal vaccine,Nano-SiO2,Zymosan, | en |
dc.relation.page | 77 | |
dc.identifier.doi | 10.6342/NTU201602576 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-105-1.pdf 目前未授權公開取用 | 2.16 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。