Adenovirus-mediated Gene Therapy for Allergy

  • Shikun Ma Department of Allergy, Peking Union Medical College Hospital, Chineses Academy of Medical Sciences and Peking Union Medical College
  • Jian Guan Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
Keywords: Adenovirus, Allergy, Gene therapy, Immunotherapy, Vaccine


Allergy poses a heavy health burden in modern society. Other than symptom-relieving medications, the only available treatment approach is allergen-specific immunotherapy, which in spite of offering a potential cure, requires a long treatment duration with multiple doses of allergen administration and carries a risk of anaphylaxis. Gene therapy has shown advantages in experimental studies for treatment of tumors, genetic diseases, chronic infections, and allergy. To date, adenovirus has been the most extensively used gene transfer vector, and offers high efficiency and safety. Here, we review studies of adenovirus-mediated gene therapy targeting different steps in the development of allergic diseases. Adenovirus-mediated gene therapy might be a promising add-on therapy for allergy treatment.

Author Biography

Shikun Ma, Department of Allergy, Peking Union Medical College Hospital, Chineses Academy of Medical Sciences and Peking Union Medical College
Department of Alergy,Attending Doctor


References: [1]. Des Roches, A., et al., Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation. Allergy, 1996. 51(6): p. 430-3. [2]. Rosenberg, S.A., et al., Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med, 1990. 323(9): p. 570-8. [3]. Chuang, Y.H., et al., Gene therapy for allergic diseases. Curr Gene Ther, 2009. 9(3): p. 185-91. [4]. Raz, E., et al., Preferential induction of a Th 1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc Natl Acad Sci U S A, 1996. 93(10): p. 5141-5. [5]. Hsu, C.H., et al., Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nat Med, 1996. 2(5): p. 540-4. [6]. Hsu, C.H., et al., Inhibition of specific IgE response in vivo by allergen-gene transfer. Int Immunol, 1996. 8(9): p. 1405-11. [7]. ROWE, W.P., et al., Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med, 1953. 84(3): p. 570-3. [8]. Gao, G.P., Y. Yang and J.M. Wilson, Biology of adenovirus vectors with E 1and E4 deletions for liver-directed gene therapy. J Virol, 1996. 70(12): p. 8934-43. [9]. Wang, Q., et al., Persistent transgene expression in mouse liver following in vivo gene transfer with a delta E1/delta E4 adenovirus vector. Gene Ther, 1997. 4(5): p. 393-400. [10]. Lowe, S.W., et al., p53 status and the efficacy of cancer therapy in vivo. Science, 1994. 266(5186): p. 807-10. [11]. Xie, Y., et al., Efficacy of adenovirus-mediated CD/5-FC and HSV-1 thymidine kinase/ganciclovir suicide gene therapies concomitant with p53 gene therapy. Clin Cancer Res, 1999. 5(12): p. 4224-32. [12]. Fooks, A.R., et al., Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents. J Gen Virol, 1998. 79 ( Pt 5): p. 1027-31. [13]. Xiang, Z.Q., et al., Oral vaccination of mice with adenoviral vectors is not impaired by preexisting immunity to the vaccine carrier. J Virol, 2003. 77(20): p. 10780-9. [14]. Hammond, J.M., et al., Oral and sub-cutaneous vaccination of commercial pigs with a recombinant porcine adenovirus expressing the classical swine fever virus gp55 gene. Arch Virol, 2001. 146(9): p. 1787-93. [15]. Fooks, A.R., et al., Induction of immunity using oral DNA vaccines expressing the measles virus nucleocapsid protein. Dev Biol (Basel), 2000. 104: p. 65-71. [16]. Pinto, A.R., et al., Induction of CD8+ T cells to an HIV-1 antigen upon oral immunization of mice with a simian E1-deleted adenoviral vector. Vaccine, 2004. 22(5-6): p. 697-703. [17]. Sharpe, S., et al., Single oral immunization with replication deficient recombinant adenovirus elicits long-lived transgene-specific cellular and humoral immune responses. Virology, 2002. 293(2): p. 210-6. [18]. Juillard, V., et al., Long-term humoral and cellular immunity induced by a single immunization with replication-defective adenovirus recombinant vector. Eur J Immunol, 1995. 25(12): p. 3467-73. [19]. Suzuki, M., et al., Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice. Hum Gene Ther, 2000. 11(6): p. 827-38. [20]. Stampfli, M.R., et al., Adenoviral infection inhibits allergic airways inflammation in mice. Clin Exp Allergy, 1998. 28(12): p. 1581-90. [21]. Hochreiter, R., et al., Prevention of allergen-specific IgE production and suppression of an established Th2-type response by immunization with DNA encoding hypoallergenic allergen derivatives of Bet v 1, the major birch-pollen allergen. Eur J Immunol, 2003. 33(6): p. 1667-76. [22]. Kay, A.B., Allergy and Allergic Diseases. 1997, Oxford: Blackwell Science. [23]. Wills-Karp, M., J. Santeliz and C.L. Karp, The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol, 2001. 1(1): p. 69-75. [24]. Herz, U., et al., Impact of in utero Th2 immunity on T cell deviation and subsequent immediate-type hypersensitivity in the neonate. Eur J Immunol, 2000. 30(2): p. 714-8. [25]. Sudowe, S., et al., Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy. Gene Ther, 2002. 9(2): p. 147-56. [26]. Yamasaki, S., et al., A single intraduodenal administration of human adenovirus 40 vaccine effectively prevents anaphylactic shock. Clin Vaccine Immunol, 2013. 20(10): p. 1508-16. [27]. Behera, A.K., et al., Adenovirus-mediated interferon gamma gene therapy for allergic asthma: involvement of interleukin 12 and STAT4 signaling. Hum Gene Ther, 2002. 13(14): p. 1697-709. [28]. Wiley, R., et al., Expression of the Th 1 chemokine IFN-gamma-inducible protein 10 in the airway alters mucosal allergic sensitization in mice. J Immunol, 2001. 166(4): p. 2750-9. [29]. Walter, D.M., et al., Il-18 gene transfer by adenovirus prevents the development of and reverses established allergen-induced airway hyperreactivity. J Immunol, 2001. 166(10): p. 6392-8. [30]. Maecker, H.T., et al., Vaccination with allergen-IL-18 fusion DNA protects against, and reverses established, airway hyperreactivity in a murine asthma model. J Immunol, 2001. 166(2): p. 959-65. [31]. Ye, Y.L., et al., Dendritic cells modulated by cytokine-expressing adenoviruses alleviate eosinophilia and airway hyperresponsiveness in an animal model of asthma. J Allergy Clin Immunol, 2004. 114(1): p. 88-96. [32]. Wang, J., et al., CD38 gene-modified dendritic cells inhibit murine asthma development by increasing IL-12 production and promoting Th 1 cell differentiation. Mol Med Rep, 2016. 14(5): p. 4374-4382. [33]. Li, Y., et al., Adenovirus expressing IFN-lambda1 (IL-29) attenuates allergic airway inflammation and airway hyperreactivity in experimental asthma. Int Immunopharmacol, 2014. 21(1): p. 156-62. [34]. Stampfli, M.R., et al., Regulation of allergic mucosal sensitization by interleukin-12 gene transfer to the airway. Am J Respir Cell Mol Biol, 1999. 21(3): p. 317-26. [35]. Hsu, C.Y., et al., Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice. J Gene Med, 2010. 12(1): p. 11-21. [36]. Li, Y., et al., Adenovirus-mediated interleukin-35 gene transfer suppresses allergic airway inflammation in a murine model of asthma. Inflamm Res, 2015. 64(10): p. 767-74. [37]. Fu, C.L., et al., Effects of adenovirus-expressing IL-10 in alleviating airway inflammation in asthma. J Gene Med, 2006. 8(12): p. 1393-9. [38]. Stampfli, M.R., et al., Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am J Respir Cell Mol Biol, 1999. 21(5): p. 586-96. [39]. Chiba, Y., et al., Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice. Am J Respir Crit Care Med, 2006. 173(9): p. 958-64. [40]. Sato, J., et al., Adenovirus-Mediated ICOSIg Gene Therapy in a Presensitized Murine Model of Allergic Rhinitis. Adv Otorhinolaryngol, 2016. 77: p. 59-66. [41]. Becker, J., et al., Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases? Fundam Clin Pharmacol, 2006. 20(5): p. 429-47. [42]. Huang, T.H., et al., The pathophysiological function of peroxisome proliferator-activated receptor-gamma in lung-related diseases. Respir Res, 2005. 6: p. 102. [43]. Narala, V.R., et al., Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma. Respir Res, 2007. 8: p. 90. [44]. Lee, K.S., et al., PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J, 2005. 19(8): p. 1033-5. [45]. Kim, S.R., et al., Involvement of IL-10 in peroxisome proliferator-activated receptor gamma-mediated anti-inflammatory response in asthma. Mol Pharmacol, 2005. 68(6): p. 1568-75. [46]. Lee, K.S., et al., Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor gamma in a murine model of toluene diisocyanate-induced asthma. J Immunol, 2006. 177(8): p. 5248-57. [47]. Lee, K.S., et al., Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice. J Allergy Clin Immunol, 2006. 118(1): p. 120-7. [48]. Park, S., et al., Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model. Exp Mol Med, 2016. 48(9): p. e259. [49]. Chuang, Y.H., et al., Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma. Gene Ther, 2004. 11(20): p. 1497-505. [50]. Chuang, Y.H., J.L. Suen and B.L. Chiang, Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen-specific T cells and airway inflammation in a murine model of asthma. J Mol Med (Berl), 2006. 84(7): p. 595-603. [51]. Wang, C.C., et al., Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma. Gene Ther, 2006. 13(19): p. 1414-21. [52]. Yin, H., et al., Adenovirus-mediated delivery of soluble ST2 attenuates ovalbumin-induced allergic asthma in mice. Clin Exp Immunol, 2012. 170(1): p. 1-9. [53]. Hu, M., et al., KyoT2 downregulates airway remodeling in asthma. Int J Clin Exp Pathol, 2015. 8(11): p. 14171-9. [54]. Huang, G.H., et al., Adenoviral delivery of recombinant soluble human tumor necrosis factor receptor 1 partially normalized mouse model of asthma. J Investig Med, 2015. 63(5): p. 765-72. [55]. Wright, J.G. and J.W. Christman, The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy. Am J Respir Med, 2003. 2(3): p. 211-9. [56]. Donovan, C.E., et al., NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J Immunol, 1999. 163(12): p. 6827-33. [57]. Beyaert, R., K. Heyninck and S. Van Huffel, A20 and A20-binding proteins as cellular inhibitors of nuclear factor-kappa B-dependent gene expression and apoptosis. Biochem Pharmacol, 2000. 60(8): p. 1143-51. [58]. El, B.K., et al., Adenoviral gene transfer of the NF-kappa B inhibitory protein ABIN-1 decreases allergic airway inflammation in a murine asthma model. J Biol Chem, 2005. 280(18): p. 17938-44. [59]. Kang, N.I., et al., A20 attenuates allergic airway inflammation in mice. J Immunol, 2009. 183(2): p. 1488-95. [60]. Nakanishi, A., et al., Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma. Proc Natl Acad Sci U S A, 2001. 98(9): p. 5175-80. [61]. Li, Y., et al., Key points of basic theories and clinical practice in rAd-p53 ( Gendicine ) gene therapy for solid malignant tumors. Expert Opin Biol Ther, 2015. 15(3): p. 437-54. [62]. Peters, W., et al., Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-gamma T cell responses in humans. Vaccine, 2013. 31(13): p. 1752-8. [63]. Rosenbaum, M.J., J.W. Poudstone and E.A. Edwards, Acceptability and antigenicity of adjuvant soluble sub-unit adenovirus vaccines in navy recruits. Mil Med, 1976. 141(6): p. 383-8. [64]. Coomes, S.M., et al., CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation. Mucosal Immunol, 2017. 10(1): p. 150-161. [65]. Guibas, G.V., M. Makris and N.G. Papadopoulos, Key regulators of sensitization and tolerance: GM-CSF, IL-10, TGF-beta and the Notch signaling pathway in adjuvant-free experimental models of respiratory allergy. Int Rev Immunol, 2013. 32(3): p. 307-23. [66]. Ng, T.H., et al., Regulation of adaptive immunity; the role of interleukin-10. Front Immunol, 2013. 4: p. 129. [67]. Yamanaka, K., et al., Restrictive IL-10 induction by an innocuous parainfluenza virus vector ameliorates nasal allergy. J Allergy Clin Immunol, 2017. 139(2): p. 682-686.e7. [68]. Kim, A.R., et al., Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice. Sci Rep, 2016. 6: p. 19685. [69]. Kunz, S., et al., T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation. Eur J Immunol, 2016. 46(8): p. 2018-27. [70]. Mueller, C., et al., The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr-/- -dependent allergy mouse model. Gene Ther, 2009. 16(2): p. 172-83. [71]. Zhao, J., et al., Improved protection of rhesus macaques against intrarectal simian immunodeficiency virus SIV(mac251) challenge by a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen. J Virol, 2003. 77(15): p. 8354-65.

How to Cite
Ma S, Guan J. Adenovirus-mediated Gene Therapy for Allergy. ijaai. 17(6):502-16.
Review Article(s)