Please use this identifier to cite or link to this item:
標題: 評估利用超音速流動力皮下遞送裸露Der p 2去氧核醣核酸疫苗抑制歐洲室塵蟎誘導之呼吸道發炎之效力
Efficacy evaluation of delivery of naked Der p 2 DNA vaccine into skin by supersonic flow for suppression of Dermatophagoides pteronyssinus-induced airway inflammation
作者: 王俊欽
Wang, Chun-Chin
關鍵字: immune
Der p 2
gene gun
出版社: 生物醫學研究所
引用: 1.Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL.Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. 2000; 343(8):538-543. 2.Busquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma: from bronchoconstriction to airway inflammation and remodeling. Am J Respir Crit Care Med. 2000; 161:1720-1745. 3.Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science. 2002; 296(5567):490-494. 4.Fanta CH. Asthma. N Engl J Med. 2009; 360(10):1002-1014. 5.Lee YL, Lin YC, Hsiue TR, Hwang BF, Guo YL. Indoor and outdoor environmental exposures, parental atopy, and physician-diagnosed asthma in Taiwanese schoolchildren. Pediatrics. 2003; 112(5):e389. 6.Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Eng J Med. 1992; 326:298-304. 7.Georas SN, Guo J, De Fanis U, Casolaro V. T-helper cell type-2 regulation in allergic disease. Eur Respir J. 2005; 26(6):1119-1137. 8.H. Heijink, D. S. Postma, JA. Noordhoek, M. Broekema, A. Kapus. House dust mite-promoted epithelial-to-mesenchymal transition in human bronchial epithelium. AJRCMB. 2009; 42(1):69-79. 9.Chou TY, Wu KY, Shieh CC, Wang JY. The clinical efficacy of in vitro allergen-specific IgE antibody test in the diagnosis of allergic children with asthma. Acta Paediatr Taiwan. 2002; 43(1):35-39. 10.Sporik R, Chapman MD, Platts-Mills TA. House dust mite exposure as a cause of asthma. Clin Exp Allergy. 1992; 22:897-906. 11.Trompette A, Divanovic S, Visintin A, Blanchard C, Hegde RS, Madan R, Thorne PS, Wills-Karp M, Gioannini TL, Weiss JP, Karp CL. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein.Nature. 2009; 457(7229):585-588. 12.Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med. 2009; 15(4):410-416. 13.Albrecht k KE, Valentine WJ, Christensen J, Vestenbaek, Palmer AJ. Sublingual Immunotherapy in Allergic Rhinitis and Asthma: A Review of Recent Clinical Evidence. The Journal of Applied Reserch. 2007; l7(1):17-31 14.Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006; 117(4):802-809. 15.Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, Rivas MF, Ribel M, Durham SR. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006; 118(2):434-440. 16.Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL. Direct gene transfer into mouse muscle in vivo. Science. 1990; 247(4949):1465-1468. 17.Bohle B. T cell responses during allergen-specific immunotherapy of Type I allergy. Biosci. 2008; 13:6079-6085. 18.Elizabeth R. J, jonathan R. L. Reversal of established CD4+ type 2 T helper-mediated allergic airway inflammation and eosinophilia by therapeutic treatment with DNA vaccines limits progression towards chronic inflammation and remodeling. Immunology. 2004; 112:631-642 19.Hartl A, Weiss R, Hochreiter R, Scheiblhofer S, Thalhamer J.DNA vaccines for allergy treatment. Methods. 2004; 32(3):328-39. 20.Hsu CH, Chua KY, Tao MH, Lai YL, Wu HD, Huang SK. Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nat Med. 1996; 2:540-544. 21.Hsu CH, Chua KY, Tao MH, Huang SK, Hsieh KH. Inhibition of specific IgE response in vivo by allergen-gene transfer. Int Immunol. 1996; 8(9):1405-1411. 22.Li GP, Liu ZG, Qiu J, Ran PX, Zhong NS. DNA vaccine encoding Der p 2 allergen generates immunologic protection in recombinant Der p 2 allergen-induced allergic airway inflammation mice model. Chin Med J (Engl). 2005; 118(7):534-540. 23.Li G, Liu Z, Zhong N, Liao B, Xiong Y. Therapeutic effects of DNA vaccine on allergen-induced allergic airway inflammation in mouse model. Cell Mol Immunol. 2006; 3(5):379-384. 24.Kwon SS, Kim NS, Yoo TJ. Vaccination with DNA encoding human T-cell epitopes suppresses Der p induced allergic responses in mice. J Asthma. 2005; 42(2):119-125. 25.Kwon SS, Kim N, Yoo TJ. The effect of vaccination with DNA encoding murine T-cell epitopes on the Der p 1 and 2 induced immunoglobulin E synthesis. Allergy 2001; 56:741-748. 26.Kim N, Kwon SS, Lee J, Kim S, Yoo TJ. Protective effect of the DNA vaccine encoding the major house dust mite allergens on allergic inflammation in the murine model of house dust mite allergy. Clin Mol Allergy. 2006; 4:4. 27.Kim CH, Ahn JH, Kim SJ, Lee SY, Kim YK, Kim KH, Moon HS, Song JS, Park SH, Kwon SS. Co-administration of vaccination with DNA encoding T cell epitope on the Der p and BCG inhibited airway remodeling in a murine model of chronic asthma. J Asthma. 2006; 43(5):345-353. 28.Li GP, Liu ZG, Liao B, Zhong NS. Induction of Th1-type immune response by chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen Der p 2 for oral vaccination in mice. Cell Mol Immunol. 2009; 6(1):45-50. 29.Tan LK, Huang CH, Kuo IC, Liew LM, Chua KY. Intramuscular immunization with DNA construct containing Der p 2 and signal peptide sequences primed strong IgE production. Vaccine. 2006; 24(29-30):5762-5771. 30.Webster RG, Robinson HL. DNA vaccines: a review of developments. BioDrugs. 1997; 8:273-292. 31.Trimble C, Lin CT, Hung CF, Pai S, Juang J, He L, Gillison M, Pardoll D, Wu L, Wu TC. Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe. Vaccine. 2003; 21:4036-4042. 32.Morel PA, Falkner D, Plowey J, Larregina AT, Falo LD. DNA immunisation: altering the cellular localisation of expressed protein and the immunisation route allows manipulation of the immune response. Vaccine. 2004; 22:447-456. 33.Lin CC, Yen MC, Lin CM, Huang SS, Yang HJ, Chow NH, Lai MD. Delivery of noncarrier naked DNA vaccine into the skin by supersonic flow induces a polarized T helper type 1 immune response to cancer. J Gene Med. 2008; 10(6):679-689. 34.von Mutius E. Allergies, infections and the hygiene hypothesis--the epidemiological evidence. Immunobiology. 2007; 212(6):433-439. 35.Takeda K, Dow SW, Miyahara N, Kodama T, Koya T, Taube C, Joetham A, Park JW, Dakhama A, Kedl RM, Gelfand EW. Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation. J Immunol. 2009; 183(1):181-190. 36.Leung DY, Bloom JW. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2003; 111(1):3-22. 37.Nasser S, Vestenbaek U, Beriot-Mathiot A, Poulsen PB. Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma. Allergy. 2008; 63(12):1624-1629. 38.Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, Riis B, Grønager PM, Durham SR. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol. 2008; 121(2):512-518. 39.Hirata H, Arima M, Yukawa T. Effects of rush immunotherapy (RIT) on cytokine production in hymenoptera allergy. Dokkyo J Med Sci.2000; 27(1):27-40. 40.Pereira-Santos MC, Baptista AP, Melo A, Alves RR, Soares RS, Pedro E, Pereira-Barbosa M, Victorino RM, Sousa AE. Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom immunotherapy. Clin Exp Allergy. 2008; 38(2):291-297. 41.Hakkaart GA, Harmsen MM, Chua KY, Thomas WR, Aalberse RC, Van Ree R. Expression of the house dust mite allergen Der p 2 in the baker''s yeast Saccharomyces cerevisiae. Clin Exp Allergy. 1998; 28(1):45-52. 42.Maggi E, Parronchi P, Manetti R, Simonelli C, Piccinni MP, Rugiu FS, De Carli M, Ricci M, Romagnani S. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992; 148(7):2142-2147. 43.Teixeira LK, Fonseca BP, Barboza BA, Viola JP. The role of interferon-gamma on immune and allergic responses. Mem Inst Oswaldo Cruz. 2005; 1:137-144. 44.Shedlock DJ, Weiner DB. DNA vaccination: antigen presentation and the induction of immunity. J Leukoc Biol. 2000; 68(6):793-806. 45.Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol. 2008; 8(12):935-947. 46.Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature. 1997; 388(6644):787-792. 47.Huang TJ, MacAry PA, Kemeny DM, Chung KF. Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats. Immunology. 1999; 96(3):416-423. 48.J. G. Martin. Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats. J. Clin. Invest. 1993; 92:1477-1482. 49.Suzuki M, Taha R, Ihaku D, Hamid Q, Martin JG. CD8+ T cells modulate late allergic airway responses in Brown Norway rats. J Immunol. 1999; 163(10):5574-5581. 50.Wells JW, Cowled CJ, Giorgini A, Kemeny DM, Noble A. Regulation of allergic airway inflammation by class I-restricted allergen presentation and CD8 T-cell infiltration. J Allergy Clin Immunol. 2007; 119(1):226-234. 51.Sarantopoulos S, Lu L, Cantor H. Qa-1 restriction of CD8+ suppressor T cells. J Clin Invest. 2004; 114(9):1218-1221. 52.O''Sullivan SM. Asthma death, CD8+ T cells, and viruses. Proc Am Thorac Soc. 2005; 2(2):162-165. 53.Miyahara N, Swanson BJ, Takeda K, Taube C, Miyahara S, Kodama T, Dakhama A, Ott VL, Gelfand EW. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med. 2004; 10(8):865-869. 54.O''Sullivan S, Cormican L, Faul JL, Ichinohe S, Johnston SL, Burke CM, Poulter LW. Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death. Am J Respir Crit Care Med. 2001; 164(4):560-564. 55.Hamelmann E, Oshiba A, Paluh J, Bradley K, Loader J, Potter TA, Larsen GL, Gelfand EW. Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization. J Exp Med. 1996; 183(4):1719-1729. 56.Miyahara N, Takeda K, Kodama T, Joetham A, Taube C, Park JW, Miyahara S, Balhorn A, Dakhama A, Gelfand EW. Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13. J Immunol. 2004; 172(4):2549-2558. 57.Cho SH, Stanciu LA, Holgate ST, Johnston SL. Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma. Am J Respir Crit Care Med. 2005; 171(3):224-230. 58.Koya T, Miyahara N, Takeda K, Matsubara S, Matsuda H, Swasey C, Balhorn A, Dakhama A, Gelfand EW. CD8+ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4+IL-4+ T cells. J Immunol. 2007; 179(5):2787-2796.
摘要: Dermatophagoides pteronyssinus group 2 (Der p 2) is a major allergen to induce allergic asthma, and is a good candidate for DNA vaccine development. Previous study suggested that intramuscular injection of plasmid DNA containing wild type Der p 2 gene induced Th1 skewed immune response. Our previous study demonstrated that novel gene gun delivering naked DNA through supersonic flow elicited similar levels of antibody and cellular response with lower dose of DNA plasmid in comparison with intramuscular injection. In addition, administration of naked DNA via novel gene gun induced a stronger Th1-skewed effect on the development of antigen-specific immune responses than traditional delivery of gold coated DNA vaccine. We focused on efficacy evaluation of naked Der p 2 DNA vaccine delivered into skin by supersonic flow for suppression of Dermatophagoides pteronyssinus- induced airway inflammation in comparison with intramuscular injection. After sensitization intraperitoneally with Der p crude extract, Balb/c mice were inoculated with naked DNA vaccine encoding Der p2 antigen by novel gene gun or intramuscular injection to protect the allergen challenges. Lung function and histological studies showed that the group of novel gene gun and intramuscular injection both reduced the airway hypersensitivity and downregulated airway inflammation. Furthermore, the vaccinated mice by gene gun showed a significant suppressed the induction of Der p and Der p2 specific immunoglobulin synthesis compared to the group of intramuscular injection. According to analysis of cell surface marker staining for intracellular cytokines, the group of gene gun had higher numbers of IFN-gamma secreting CD4 and IFN-gamma secreting CD8 T cells than intramuscular injection and significantly attenuated the numbers of IL-4 secreting CD4 T cells in spleen cells. Thus, we suggest that novel gene gun significantly increases the Der p 2-specific anti-airway inflammation Th1 immune response and has better efficacy to protect the asthmatic antigen exposures than intramuscular administration. The results also provided the immunological rationale for testing delivery of naked Der p 2 DNA vaccine into skin via novel gene gun in patients with Dermatophagoides pteronyssinus induced airway inflammation.
歐洲室塵蟎第2群抗原(Der p 2)是引起肺部氣喘的主要過敏原,因此也是作為去氧核糖核酸疫苗研製中一個好的候選抗原。而先前的研究已證實,利用肌肉注射野生型的Der p 2的DNA疫苗可在動物體內誘導第一型輔助T細胞(Th1)偏差的免疫反應。在我們之前的研究發現使用超音速流動力遞送裸露去氧核糖核酸進入皮膚層,不僅可以在較低的用量下誘導出與利用肌肉注射相似的抗體型及免疫型反應,相較於傳統金屬包裹之去氧核糖核酸疫苗,新式基因槍遞送裸露DNA疫苗的策略,可明顯誘導出非常強的抗原專一性Th1細胞型免疫反應。我們目標評估利用超音速流動力遞送裸露Der p 2去氧核糖核酸疫苗至皮下,與肌肉注射方式,比較抑制Der p誘發之呼吸道發炎之能力。在實驗設計上, Balb/c小鼠以歐洲室塵蟎粗萃物致敏後,利用基因槍施打或是肌肉注射來接種裸核DNA疫苗來抵抗過敏原的暴露。根據肺功能測試和組織染色與切片,Der p 2誘導之呼吸道發炎之小鼠肺部氣喘程度,施打新式基因槍方式和肌肉注射均降底小鼠氣喘引起的呼吸道敏感和發炎情形。進一步研究上發現,與肌肉注射作比較,利用基因槍遞送裸露Der p 2 之DNA疫苗更能顯著的抑制Der p和Der p 2特定免疫球蛋白;經由細胞內細胞素染色分析,相較於肌肉注射,施打新式基因槍方式提昇脾臟細胞內的分泌INF-gamma 的CD4及CD8之T細胞和顯著減弱分泌IL-4的CD4之T細胞數目。因此,我們的實驗證實了新式基因槍施打Der p 2 DNA疫苗顯著的增加專一性Der p 2的Th1免疫反應去抑制過敏性免疫反應,且比肌肉注射的方式有較強的效力去保護造成氣喘的過敏原暴露。實驗結果可以提供免疫上的原理,運用於新式基因槍皮下遞送裸露Der p 2之DNA疫苗治療塵螨引起之過敏病患。
其他識別: U0005-1808201012125000
Appears in Collections:生物醫學研究所



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.