Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Strategies of mucosal immunotherapy for allergic diseases

Cellular & Molecular Immunology volume 8, pages 453–461 (2011)Cite this article

Abstract

Incidences of allergic disease have recently increased worldwide. Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases. Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT), there remains a risk of severe and sometimes fatal anaphylaxis. Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J . Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy 2006; 36: 402–425.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Togias A . Mechanisms of nose-lung interaction. Allergy 1999; 54 ( Suppl 57): 94–105.

    PubMed  Google Scholar 

  3. Passalacqua G, Ciprandi G, Canonica GW . United airways disease: therapeutic aspects. Thorax 2000; 55 ( Suppl 2): S26–S27.

    PubMed  PubMed Central  Google Scholar 

  4. Passalacqua G, Ciprandi G, Canonica GW . The nose–lung interaction in allergic rhinitis and asthma: united airways disease. Curr Opin Allergy Clin Immunol 2001; 1: 7–13.

    CAS  PubMed  Google Scholar 

  5. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008; 63 ( Suppl 86): 8–160.

    PubMed  Google Scholar 

  6. Linneberg A, Henrik Nielsen N, Frolund L, Madsen F, Dirksen A, Jorgensen T . The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study. Allergy 2002; 57: 1048–1052.

    CAS  PubMed  Google Scholar 

  7. Zheng T, Yu J, Oh MH, Zhu Z . The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res 2011; 3: 67–73.

    PubMed  PubMed Central  Google Scholar 

  8. Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol 2006; 118: 152–169.

    PubMed  Google Scholar 

  9. Greiner AN, Meltzer EO . Overview of the treatment of allergic rhinitis and nonallergic rhinopathy. Proc Am Thorac Soc 2011; 8: 121–131.

    CAS  PubMed  Google Scholar 

  10. Chung KF, Caramori G, Adcock IM . Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future. Eur J Clin Pharmacol 2009; 65: 853–871.

    CAS  PubMed  Google Scholar 

  11. Papi A . Treatment strategies in mild asthma. Curr Opin Pulm Med 2009; 15: 29034.

    PubMed  Google Scholar 

  12. Pedersen S . Do inhaled corticosteroids inhibit growth in children? Am J Respir Crit Care Med 2001; 164: 521–535.

    CAS  PubMed  Google Scholar 

  13. Heaney LG, Robinson DS . Severe asthma treatment: need for characterising patients. Lancet 2005; 365: 974–976.

    PubMed  Google Scholar 

  14. Wenzel S . Severe asthma in adults. Am J Respir Crit Care Med 2005; 172: 149–160.

    PubMed  Google Scholar 

  15. Nagai H, Teramachi H, Tuchiya T . Recent advances in the development of anti-allergic drugs. Allergol Int 2006; 55: 35–42.

    CAS  PubMed  Google Scholar 

  16. Chen Y, Inobe J, Marks R, Gonnella P, Kuchroo VK, Weiner HL . Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 1995; 376: 177–180.

    CAS  PubMed  Google Scholar 

  17. Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1998; 81: 401–405.

    CAS  PubMed  Google Scholar 

  18. Marth T, Zeitz Z, Ludviksson B, Strober W, Kelsall B . Murine model of oral tolerance. Induction of Fas-mediated apoptosis by blockade of interleukin-12. Ann NY Acad Sci 1998; 859: 290–294.

    CAS  PubMed  Google Scholar 

  19. Inobe J, Slavin AJ, Komagata Y, Chen Y, Liu L, Weiner HL . IL-4 is a differentiation factor for transforming growth factor-beta secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. Eur J Immunol 1998; 28: 2780–2790.

    CAS  PubMed  Google Scholar 

  20. Weiner HL . Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 2001; 182: 207–214.

    CAS  PubMed  Google Scholar 

  21. Abramson MJ, Puy RM, Weiner JM . Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev 2010; (8): CD001186.

    Google Scholar 

  22. Rank MA, Li JT . Allergen immunotherapy. Mayo Clin Proc 2007; 82: 1119–1123.

    PubMed  Google Scholar 

  23. Passalacqua G, Durham SR . Allergic rhinitis and its impact on asthma update: allergen immunotherapy. J Allergy Clin Immunol 2007; 119: 881–891.

    PubMed  Google Scholar 

  24. Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy 2006; 61: 202–205.

    CAS  PubMed  Google Scholar 

  25. Holmgren J, Czerkinsky C . Mucosal immunity and vaccines. Nat Med 2005; 11: S45–S53.

    CAS  PubMed  Google Scholar 

  26. Akbari O, DeKruyff RH, Umetsu DT . Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001; 2: 725–731.

    CAS  PubMed  Google Scholar 

  27. Schroder NW . The role of innate immunity in the pathogenesis of asthma. Curr Opin Allergy Clin Immunol 2009; 9: 38–43.

    PubMed  Google Scholar 

  28. Holgate ST . Pathogenesis of asthma. Clin Exp Allergy 2008; 38: 872–897.

    CAS  PubMed  Google Scholar 

  29. Hufnagl K, Focke M, Gruber F, Hufnagl P, Loupal G, Scheiner O et al. Airway inflammation induced after allergic poly-sensitization can be prevented by mucosal but not by systemic administration of poly-peptides. Clin Exp Allergy 2008; 38: 1192–1202.

    CAS  PubMed  Google Scholar 

  30. Mowat AM . Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003; 3: 331–341.

    CAS  PubMed  Google Scholar 

  31. Wu HY, Weiner HL . Oral tolerance. Immunol Res 2003; 28: 265–284.

    PubMed  Google Scholar 

  32. Mayer L, Shao L . Therapeutic potential of oral tolerance. Nat Rev Immunol 2004; 4: 407–419.

    CAS  PubMed  Google Scholar 

  33. Appleman LJ, Boussiotis VA . T cell anergy and costimulation. Immunol Rev 2003; 192: 161–180.

    CAS  PubMed  Google Scholar 

  34. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737–742.

    CAS  PubMed  Google Scholar 

  35. Battaglia M, Blazar BR, Roncarolo MG . The puzzling world of murine T regulatory cells. Microbes Infect 2002; 4: 559–566.

    CAS  PubMed  Google Scholar 

  36. Groux H . Type 1 T-regulatory cells: their role in the control of immune responses. Transplantation 2003; 75: 8S–12S.

    CAS  PubMed  Google Scholar 

  37. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001; 182: 18–32.

    CAS  PubMed  Google Scholar 

  38. Thorstenson KM, Khoruts A . Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J Immunol 2001; 167: 188–195.

    CAS  PubMed  Google Scholar 

  39. Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL, Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992; 89: 421–425.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Horwitz DA, Zheng SG, Gray JD . The role of the combination of IL-2 and TGF-beta or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets. J Leukoc Biol 2003; 74: 471–478.

    CAS  PubMed  Google Scholar 

  41. Wan YY . Regulatory T cells: immune suppression and beyond. Cell Mol Immunol 2010; 7: 204–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Valenta R, Lidholm J, Niederberger V, Hayek B, Kraft D, Gronlund H . The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999; 29: 896–904.

    CAS  PubMed  Google Scholar 

  43. Wiedermann U . Prophylaxis and therapy of allergy by mucosal tolerance induction with recombinant allergens or allergen constructs. Curr Drug Targets Inflamm Allergy 2005; 4: 577–583.

    CAS  PubMed  Google Scholar 

  44. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci USA 2004; 101 ( Suppl 2): 14677–14682.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hoyne GF, O'Hehir RE, Wraith DC, Thomas WR, Lamb JR . Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice. J Exp Med 1993; 178: 1783–1788.

    CAS  PubMed  Google Scholar 

  46. Hufnagl K, Winkler B, Focke M, Valenta R, Scheiner O, Renz H et al. Intranasal tolerance induction with polypeptides derived from 3 noncross-reactive major aeroallergens prevents allergic polysensitization in mice. J Allergy Clin Immunol 2005; 116: 370–376.

    CAS  PubMed  Google Scholar 

  47. Petrarca C, Lazzarin F, Pannellini T, Iezzi M, Braga M, Mistrello G et al. Monomeric allergoid intragastric administration induces local and systemic tolerogenic response involving IL-10-producing CD4+CD25+ T regulatory cells in mice. Int J Immunopathol Pharmacol 2010; 23: 1021–1031.

    CAS  PubMed  Google Scholar 

  48. Gammeri E, Arena A, D'Anneo R, La Grutta S . Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma. Allergol Immunopathol (Madr) 2005; 33: 221–223.

    CAS  Google Scholar 

  49. Gammeri E, Arena A, D'Anneo R, La Grutta S . Safety and tolerability of ultra-Rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma. Allergol Immunopathol (Madr) 2005; 33: 142–144.

    CAS  Google Scholar 

  50. Takagi H, Hiroi T, Yang L, Tada Y, Yuki Y, Takamura K et al. A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proc Natl Acad Sci USA 2005; 102: 17525–17530.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Sun JB, Holmgren J, Czerkinsky C . Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance. Proc Natl Acad Sci USA 1994; 91: 10795–10799.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Smits HH, Gloudemans AK, van Nimwegen M, Willart MA, Soullie T, Muskens F et al. Cholera toxin B suppresses allergic inflammation through induction of secretory IgA. Mucosal Immunol 2009; 2: 331–339.

    CAS  PubMed  Google Scholar 

  53. Hirose I, Tanaka H, Takahashi G, Wakahara K, Tamari M, Sakamoto T et al. Immunomodulatory effects of CpG oligodeoxynucleotides on house dust mite-induced airway inflammation in mice. Int Arch Allergy Immunol 2008; 147: 6–16.

    CAS  PubMed  Google Scholar 

  54. Krieg AM . CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 709–760.

    CAS  PubMed  Google Scholar 

  55. Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM . CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. Proc Natl Acad Sci USA 1996; 93: 2879–2883.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Fonseca DE, Kline JN . Use of CpG oligonucleotides in treatment of asthma and allergic disease. Adv Drug Deliv Rev 2009; 61: 256–262.

    CAS  PubMed  Google Scholar 

  57. Shirota H, Sano K, Kikuchi T, Tamura G, Shirato K . Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs. Am J Respir Cell Mol Biol 2000; 22: 176–182.

    CAS  PubMed  Google Scholar 

  58. Hayashi T, Beck L, Rossetto C, Gong X, Takikawa O, Takabayashi K et al. Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. J Clin Invest 2004; 114: 270–279.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ et al. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J Immunol 2004; 173: 4433–4442.

    CAS  PubMed  Google Scholar 

  60. Oldenhove G, de Heusch M, Urbain-Vansanten G, Urbain J, Maliszewski C, Leo O et al. CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo. J Exp Med 2003; 198: 259–266.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Ramaprakash H, Hogaboam CM . Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner. Int Arch Allergy Immunol 2009; 152: 98–112.

    PubMed  PubMed Central  Google Scholar 

  62. Tulic MK, Fiset PO, Christodoulopoulos P, Vaillancourt P, Desrosiers M, Lavigne F et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol 2004; 113: 235–241.

    CAS  PubMed  Google Scholar 

  63. Allergen immunotherapy: therapeutic vaccines for allergic diseases. Geneva: January 27–29 1997. Allergy 1998; 53 ( Suppl 44) : 1–42.

  64. Gauvreau GM, Hessel EM, Boulet LP, Coffman RL, O'Byrne PM . Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am J Respir Crit Care Med 2006; 174: 15–20.

    CAS  PubMed  Google Scholar 

  65. Davis HL, Suparto II, Weeratna RR, Jumintarto, Iskandriati DD, Chamzah SS et al. CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans. Vaccine 2000; 18: 1920–1924.

    CAS  PubMed  Google Scholar 

  66. Vollmer J . Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9. Expert Opin Biol Ther 2005; 5: 673–682.

    CAS  PubMed  Google Scholar 

  67. Synowiecki J, Al-Khateeb NA . Production, properties, and some new applications of chitin and its derivatives. Crit Rev Food Sci Nutr 2003; 43: 145–171.

    CAS  PubMed  Google Scholar 

  68. Biagini G, Muzzarelli RA, Giardino R, Castaldini C . Advances in Chitin and Chitosan. New York: Elsevier Applied Science, 1992.

    Google Scholar 

  69. Burton OT, Zaccone P . The potential role of chitin in allergic reactions. Trends Immunol 2007; 28: 419–422.

    CAS  PubMed  Google Scholar 

  70. Shibata Y, Foster LA, Bradfield JF, Myrvik QN . Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse. J Immunol 2000; 164: 1314–1321.

    CAS  PubMed  Google Scholar 

  71. Strong P, Clark H, Reid K . Intranasal application of chitin microparticles down-regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy. Clin Exp Allergy 2002; 32: 1794–1800.

    CAS  PubMed  Google Scholar 

  72. Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L et al. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science 2004; 304: 1678–1682.

    CAS  PubMed  Google Scholar 

  73. Reese TA, Liang HE, Tager AM, Luster AD, van Rooijen N, Voehringer D et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 2007; 447: 92–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Lee CG . Chitin, chitinases and chitinase-like proteins in allergic inflammation and tissue remodeling. Yonsei Med J 2009; 50: 22–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Tsigos I, Bouriotis V . Purification and characterization of chitin deacetylase from Colletotrichum lindemuthianum. J Biol Chem 1995; 270: 26286–26291.

    CAS  PubMed  Google Scholar 

  76. Angelova N, Hunkeler D . Effect of preparation conditions on properties and permeability of chitosan–sodium hexametaphosphate capsules. J Biomater Sci Polym Ed 2001; 12: 1317–1337.

    CAS  PubMed  Google Scholar 

  77. Chen CL, Wang YM, Liu CF, Wang JY . The effect of water-soluble chitosan on macrophage activation and the attenuation of mite allergen-induced airway inflammation. Biomaterials 2008; 29: 2173–2182.

    CAS  PubMed  Google Scholar 

  78. Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME . Probiotics and immunity. J Gastroenterol 2009; 44: 26–46.

    PubMed  Google Scholar 

  79. Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, MacDermott RP et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 1993; 94: 174–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E . Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001; 357: 1076–1079.

    CAS  PubMed  Google Scholar 

  81. Feleszko W, Jaworska J, Rha RD, Steinhausen S, Avagyan A, Jaudszus A et al. Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 2007; 37: 498–505.

    CAS  PubMed  Google Scholar 

  82. Forsythe P, Inman MD, Bienenstock J . Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med 2007; 175: 561–569.

    PubMed  Google Scholar 

  83. Penders J, Stobberingh EE, van den Brandt PA, Thijs C . The role of the intestinal microbiota in the development of atopic disorders. Allergy 2007; 62: 1223–1236.

    CAS  PubMed  Google Scholar 

  84. Lee J, Seto D, Bielory L . Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol 2008; 121: 116–121.

    PubMed  Google Scholar 

  85. Kawase M, He F, Kubota A, Hiramatsu M, Saito H, Ishii T et al. Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study. Int J Food Microbiol 2009; 128: 429–434.

    CAS  PubMed  Google Scholar 

  86. Nagata Y, Yoshida M, Kitazawa H, Araki E, Gomyo T . Improvements in seasonal allergic disease with Lactobacillus plantarum No. 14. Biosci Biotechnol Biochem 2010; 74: 1869–1877.

    CAS  PubMed  Google Scholar 

  87. Tang ML, Lahtinen SJ, Boyle RJ . Probiotics and prebiotics: clinical effects in allergic disease. Curr Opin Pediatr 2010; 22: 626–634.

    PubMed  Google Scholar 

  88. van de Pol MA, Lutter R, Smids BS, Weersink EJ, van der Zee JS . Synbiotics reduce allergen-induced T-helper 2 response and improve peak expiratory flow in allergic asthmatics. Allergy 2011; 66: 39–47.

    CAS  PubMed  Google Scholar 

  89. Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E . High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatr Allergy Immunol 2010; 21 ( Pt 1): 67–73.

    PubMed  Google Scholar 

  90. Pan SJ, Kuo CH, Lam KP, Chu YT, Wang WL, Hung CH . Probiotics and allergy in children—an update review. Pediatr Allergy Immunol 2010; 21: e659–e666.

    PubMed  Google Scholar 

  91. Rask C, Holmgren J, Fredriksson M, Lindblad M, Nordstrom I, Sun JB et al. Prolonged oral treatment with low doses of allergen conjugated to cholera toxin B subunit suppresses immunoglobulin E antibody responses in sensitized mice. Clin Exp Allergy 2000; 30: 1024–1032.

    CAS  PubMed  Google Scholar 

  92. Lee CH, Mo JH . Recent advances in immunotherapy of allergic rhinitis. Curr Allergy Asthma Rep 2008; 8: 269–271.

    CAS  PubMed  Google Scholar 

  93. Wiedermann U, Jahn-Schmid B, Lindblad M, Rask C, Holmgren J, Kraft D et al. Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy. Int Immunol 1999; 11: 1131–1138.

    CAS  PubMed  Google Scholar 

  94. Sun JB, Czerkinsky C, Holmgren J . Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit. Scand J Immunol 2010; 71: 1–11.

    CAS  PubMed  Google Scholar 

  95. Shirota H, Sano K, Kikuchi T, Tamura G, Shirato K . Regulation of murine airway eosinophilia and Th2 cells by antigen-conjugated CpG oligodeoxynucleotides as a novel antigen-specific immunomodulator. J Immunol 2000; 164: 5575–5582.

    CAS  PubMed  Google Scholar 

  96. Hussain I, Kline JN . DNA, the immune system, and atopic disease. J Investig Dermatol Symp Proc 2004; 9: 23–28.

    CAS  PubMed  Google Scholar 

  97. Gupta GK, Agrawal DK . CpG oligodeoxynucleotides as TLR9 agonists: therapeutic application in allergy and asthma. BioDrugs 2010; 24: 225–235.

    CAS  PubMed  Google Scholar 

  98. Liu Z, Guo H, Wu Y, Yu H, Yang H, Li J . Local nasal immunotherapy: efficacy of Dermatophagoides farinae–chitosan vaccine in murine asthma. Int Arch Allergy Immunol 2009; 150: 221–228.

    CAS  PubMed  Google Scholar 

  99. Saint-Lu N, Tourdot S, Razafindratsita A, Mascarell L, Berjont N, Chabre H et al. Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance induction. Allergy 2009; 64: 1003–1013.

    CAS  PubMed  Google Scholar 

  100. 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: 45–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Chew JL, Wolfowicz CB, Mao HQ, Leong KW, Chua KY . Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine 2003; 21: 2720–2729.

    CAS  PubMed  Google Scholar 

  102. Matsuzaki T, Yamazaki R, Hashimoto S, Yokokura T . The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice. J Dairy Sci 1998; 81: 48–53.

    CAS  PubMed  Google Scholar 

  103. Shida K, Takahashi R, Iwadate E, Takamizawa K, Yasui H, Sato T et al. Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model. Clin Exp Allergy 2002; 32: 563–570.

    CAS  PubMed  Google Scholar 

  104. Repa A, Grangette C, Daniel C, Hochreiter R, Hoffmann-Sommergruber K, Thalhamer J et al. Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy. Vaccine 2003; 22: 87–95.

    CAS  PubMed  Google Scholar 

  105. Kruisselbrink A, Heijne Den Bak-Glashouwer MJ, Havenith CE, Thole JE, Janssen R . Recombinant Lactobacillus plantarum inhibits house dust mite-specific T-cell responses. Clin Exp Immunol 2001; 126: 2–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Daniel C, Repa A, Mercenier A, Wiedermann U, Wells J . The European LABDEL project and its relevance to the prevention and treatment of allergies. Allergy 2007; 62: 1237–1242.

    CAS  PubMed  Google Scholar 

  107. Daniel C, Repa A, Wild C, Pollak A, Pot B, Breiteneder H et al. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1. Allergy 2006; 61: 812–819.

    CAS  PubMed  Google Scholar 

  108. Ma Y, Ma AG, Peng Z . A potential immunotherapy approach: mucosal immunization with an IL-13 peptide-based virus-like particle vaccine in a mouse asthma model. Vaccine 2007; 25: 8091–8099.

    CAS  PubMed  Google Scholar 

  109. Kumar M, Kong X, Behera AK, Hellermann GR, Lockey RF, Mohapatra SS . Chitosan IFN-gamma-pDNA nanoparticle (CIN) therapy for allergic asthma. Genet Vaccines Ther 2003; 1: 3.

    PubMed  PubMed Central  Google Scholar 

  110. Cortes-Perez NG, Ah-Leung S, Bermudez-Humaran LG, Corthier G, Wal JM, Langella P et al. Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice. Clin Vaccine Immunol 2007; 14: 226–233.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. van Overtvelt L, Lombardi V, Razafindratsita A, Saint-Lu N, Horiot S, Moussu H et al. IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model. Int Arch Allergy Immunol 2008; 145: 152–162.

    CAS  PubMed  Google Scholar 

  112. Tighe H, Corr M, Roman M, Raz E . Gene vaccination: plasmid DNA is more than just a blueprint. Immunol Today 1998; 19: 89–97.

    CAS  PubMed  Google Scholar 

  113. Shin JH, Kang JM, Kim SW, Cho JH, Park YJ . Effect of oral tolerance in a mouse model of allergic rhinitis. Otolaryngol Head Neck Surg 2010; 142: 370–375.

    PubMed  Google Scholar 

  114. Xie QM, Wu X, Wu HM, Deng YM, Zhang SJ, Zhu JP et al. Oral administration of allergen extracts from Dermatophagoides farinae desensitizes specific allergen-induced inflammation and airway hyperresponsiveness in rats. Int Immunopharmacol 2008; 8: 1639–1645.

    CAS  PubMed  Google Scholar 

  115. Faria AM, Weiner HL . Oral tolerance. Immunol Rev 2005; 206: 232–259.

    CAS  PubMed  Google Scholar 

  116. Faria AM, Maron R, Ficker SM, Slavin AJ, Spahn T, Weiner HL . Oral tolerance induced by continuous feeding: enhanced up-regulation of transforming growth factor-beta/interleukin-10 and suppression of experimental autoimmune encephalomyelitis. J Autoimmun 2003; 20: 135–145.

    CAS  PubMed  Google Scholar 

  117. Slavin AJ, Maron R, Weiner HL . Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes. Int Immunol 2001; 13: 825–833.

    CAS  PubMed  Google Scholar 

  118. Marth T, Strober W, Kelsall BL . High dose oral tolerance in ovalbumin TCR-transgenic mice: systemic neutralization of IL-12 augments TGF-beta secretion and T cell apoptosis. J Immunol 1996; 157: 2348–2357.

    CAS  PubMed  Google Scholar 

  119. Thorbecke GJ, Schwarcz R, Leu J, Huang C, Simmons WJ . Modulation by cytokines of induction of oral tolerance to type II collagen. Arthritis Rheum 1999; 42: 110–118.

    CAS  PubMed  Google Scholar 

  120. Edwan JH, Perry G, Talmadge JE, Agrawal DK . Flt-3 ligand reverses late allergic response and airway hyper-responsiveness in a mouse model of allergic inflammation. J Immunol 2004; 172: 5016–5023.

    CAS  PubMed  Google Scholar 

  121. Hanninen A, Martinez NR, Davey GM, Heath WR, Harrison LC . Transient blockade of CD40 ligand dissociates pathogenic from protective mucosal immunity. J Clin Invest 2002; 109: 261–267.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Allam JP, Wurtzen PA, Reinartz M, Winter J, Vrtala S, Chen KW et al. Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties. J Allergy Clin Immunol 2010; 126: 638–645.

    CAS  PubMed  Google Scholar 

  123. Taudorf E, Laursen LC, Djurup R, Kappelgaard E, Pedersen CT, Soborg M et al. Oral administration of grass pollen to hay fever patients. An efficacy study in oral hyposensitization. Allergy 1985; 40: 321–335.

    CAS  PubMed  Google Scholar 

  124. Taudorf E, Laursen LC, Lanner A, Bjorksten B, Dreborg S, Soborg M et al. Oral immunotherapy in birch pollen hay fever. J Allergy Clin Immunol 1987; 80: 153–161.

    CAS  PubMed  Google Scholar 

  125. Canonica GW, Passalacqua G . Noninjection routes for immunotherapy. J Allergy Clin Immunol 2003; 111: 437–448.

    PubMed  Google Scholar 

  126. Haneda K, Sano K, Tamura G, Shirota H, Ohkawara Y, Sato T et al. Transforming growth factor-beta secreted from CD4+ T cells ameliorates antigen-induced eosinophilic inflammation. A novel high-dose tolerance in the trachea. Am J Respir Cell Mol Biol 1999; 21: 268–274.

    CAS  PubMed  Google Scholar 

  127. Hoyne GF, Askonas BA, Hetzel C, Thomas WR, Lamb JR . Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. Int Immunol 1996; 8: 335–342.

    CAS  PubMed  Google Scholar 

  128. Hoyne GF, O'Hehir RE, Wraith DC, Thomas WR, Lamb JR . Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice. J Exp Med 1993; 178: 1783–1788.

    CAS  PubMed  Google Scholar 

  129. Marcucci F, Sensi LG, Caffarelli C, Cavagni G, Bernardini R, Tiri A et al. Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides. Allergy 2002; 57: 23–28.

    CAS  PubMed  Google Scholar 

  130. Pocobelli D, del Bono A, Venuti L, Falagiani P, Venuti A . Nasal immunotherapy at constant dosage: a double-blind, placebo-controlled study in grass-allergic rhinoconjunctivitis. J Investig Allergol Clin Immunol 2001; 11: 79–88.

    CAS  PubMed  Google Scholar 

  131. Bjorksten B . Local immunotherapy is not documented for clinical use. Allergy 1994; 49: 299–301.

    CAS  PubMed  Google Scholar 

  132. Crimi E, Voltolini S, Troise C, Gianiorio P, Crimi P, Brusasco V et al. Local immunotherapy with Dermatophagoides extract in asthma. J Allergy Clin Immunol 1991; 87: 721–728.

    CAS  PubMed  Google Scholar 

  133. Tari MG, Mancino M, Monti G . Immunotherapy by inhalation of allergen in powder in house dust allergic asthma—a double-blind study. J Investig Allergol Clin Immunol 1992; 2: 59–67.

    CAS  PubMed  Google Scholar 

  134. Markert UR . Local immunotherapy in allergy: prospects for the future. Chem Immunol Allergy 2003; 82: 127–135.

    PubMed  Google Scholar 

  135. Ozdemir C . An immunological overview of allergen specific immunotherapy—subcutaneous and sublingual routes. Ther Adv Respir Dis 2009; 3: 253–262.

    PubMed  Google Scholar 

  136. O'Hehir RE, Sandrini A, Anderson GP, Rolland JM . Sublingual allergen immunotherapy: immunological mechanisms and prospects for refined vaccine preparation. Curr Med Chem 2007; 14: 2235–2244.

    CAS  PubMed  Google Scholar 

  137. Bohle B, Kinaciyan T, Gerstmayr M, Radakovics A, Jahn-Schmid B, Ebner C . Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol 2007; 120: 707–713.

    CAS  PubMed  Google Scholar 

  138. Akdis CA, Barlan IB, Bahceciler N, Akdis M . Immunological mechanisms of sublingual immunotherapy. Allergy 2006; 61 ( Suppl 81): 11–14.

    PubMed  Google Scholar 

  139. O'Hehir RE, Gardner LM, de Leon MP, Hales BJ, Biondo M, Douglass JA et al. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. Am J Respir Crit Care Med 2009; 180: 936–947.

    CAS  PubMed  Google Scholar 

  140. Scadding G, Durham S . Mechanisms of sublingual immunotherapy. J Asthma 2009; 46: 322–334.

    CAS  PubMed  Google Scholar 

  141. Brimnes J, Kildsgaard J, Jacobi H, Lund K . Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis. Clin Exp Allergy 2007; 37: 488–497.

    CAS  PubMed  Google Scholar 

  142. Eberlein-Konig B, Jung C, Rakoski J, Ring J . Immunohistochemical investigation of the cellular infiltrates at the sites of allergoid-induced late-phase cutaneous reactions associated with pollen allergen-specific immunotherapy. Clin Exp Allergy 1999; 29: 1641–1647.

    CAS  PubMed  Google Scholar 

  143. Wilson DR, Lima MT, Durham SR . Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 2005; 60: 4–12.

    CAS  PubMed  Google Scholar 

  144. Marcucci F, Sensi L, Incorvaia C, Di Cara G, Moingeon P, Frati F . Oral reactions to sublingual immunotherapy: a bioptic study. Allergy 2007; 62: 1475–1477.

    CAS  PubMed  Google Scholar 

  145. Marcucci F, Sensi L, Di Cara G, Gidaro G, Incorvaia C, Frati F . Sublingual reactivity to rBET V1 and rPHL P1 in patients with oral allergy syndrome. Int J Immunopathol Pharmacol 2006; 19: 141–148.

    CAS  PubMed  Google Scholar 

  146. Stelmach I, Kaczmarek-Wozniak J, Majak P, Olszowiec-Chlebna M, Jerzynska J . Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen. Clin Exp Allergy 2009; 39: 401–408.

    CAS  PubMed  Google Scholar 

  147. Cao LF, Lu Q, Gu HL, Chen YP, Zhang Y, Lu M et al. Clinical evaluation for sublingual immunotherapy of allergic asthma and atopic rhinitis with Dermatophagoides Farinae Drops. Zhonghua Er Ke Za Zhi 2007; 45: 736–741. Chinese.

    PubMed  Google Scholar 

  148. Agostinis F, Foglia C, Landi M, Cottini M, Lombardi C, Canonica GW et al. The safety of sublingual immunotherapy with one or multiple pollen allergens in children. Allergy 2008; 63: 1637–1639.

    CAS  PubMed  Google Scholar 

  149. Cochard MM, Eigenmann PA . Sublingual immunotherapy is not always a safe alternative to subcutaneous immunotherapy. J Allergy Clin Immunol 2009; 124: 378–379.

    PubMed  Google Scholar 

  150. Larenas-Linnemann D . Sublingual immunotherapy in children: complete and updated review supporting evidence of effect. Curr Opin Allergy Clin Immunol 2009; 9: 168–176.

    PubMed  Google Scholar 

  151. Esch RE, Bush RK, Peden D, Lockey RF . Sublingual-oral administration of standardized allergenic extracts: phase 1 safety and dosing results. Ann Allergy Asthma Immunol 2008; 100: 475–481.

    PubMed  Google Scholar 

  152. Nuhoglu Y, Ozumut SS, Ozdemir C, Ozdemir M, Nuhoglu C, Erguven M . Sublingual immunotherapy to house dust mite in pediatric patients with allergic rhinitis and asthma: a retrospective analysis of clinical course over a 3-year follow-up period. J Investig Allergol Clin Immunol 2007; 17: 375–378.

    CAS  PubMed  Google Scholar 

  153. Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de Beaumont O et al. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol 2009; 123: 160–166.

    CAS  PubMed  Google Scholar 

  154. Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 2009; 123: 167–173.

    CAS  PubMed  Google Scholar 

  155. Fiocchi A, Fox AT . Preventing progression of allergic rhinitis: the role of specific immunotherapy. Arch Dis Child Educ Pract Ed 2011; 96: 91–100.

    PubMed  Google Scholar 

  156. Broide DH . Immunomodulation of allergic disease. Annu Rev Med 2009; 60: 279–291.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 2010; 40: 922–932.

    CAS  PubMed  Google Scholar 

  158. Pham-Thi N, Scheinmann P, Fadel R, Combebias A, Andre C . Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures. Pediatr Allergy Immunol 2007; 18: 47–57.

    PubMed  Google Scholar 

  159. Compalati E, Passalacqua G, Bonini M, Canonica GW . The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis. Allergy 2009; 64: 1570–1579.

    CAS  PubMed  Google Scholar 

  160. Rodriguez Santos O . Sublingual immunotherapy in allergic rhinitis and asthma in 2–5 year-old children sensitized to mites. Rev Alerg Mex 2008; 55: 71–75. Spanish.

    PubMed  Google Scholar 

  161. Alche JD, Castro AJ, Jimenez-Lopez JC, Morales S, Zafra A, Hamman-Khalifa AM et al. Differential characteristics of olive pollen from different cultivars: biological and clinical implications. J Investig Allergol Clin Immunol 2007; 17 ( Suppl 1): 17–23.

    CAS  PubMed  Google Scholar 

  162. Radulovic S, Wilson D, Calderon M, Durham S . Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66: 740–752.

    CAS  PubMed  Google Scholar 

  163. Marogna M, Colombo F, Cerra C, Bruno M, Massolo A, Canonica GW et al. The clinical efficacy of a sublingual monomeric allergoid at different maintenance doses: a randomized controlled trial. Int J Immunopathol Pharmacol 2010; 23: 937–945.

    CAS  PubMed  Google Scholar 

  164. Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol 2007; 120: 164–170.

    CAS  PubMed  Google Scholar 

  165. Takai T, Ikeda S . Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases. Allergol Int 2011; 60: 25–35.

    CAS  PubMed  Google Scholar 

  166. Akdis M, Blaser K, Akdis CA . T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol 2005; 116: 961–968.

    CAS  PubMed  Google Scholar 

  167. Wohlleben G, Erb KJ . Atopic disorders: a vaccine around the corner? Trends Immunol 2001; 22: 618–626.

    CAS  PubMed  Google Scholar 

  168. Lee CC, Chiang BL . RNA interference: new therapeutics in allergic diseases. Curr Gene Ther 2008; 8: 236–246.

    CAS  PubMed  Google Scholar 

  169. Wang LC, Lee JH, Yang YH, Lin YT, Chiang BL . New biological approaches in asthma: DNA-based therapy. Curr Med Chem 2007; 14: 1607–1618.

    CAS  PubMed  Google Scholar 

  170. Chuang YH, Yang YH, Wu SJ, Chiang BL . Gene therapy for allergic diseases. Curr Gene Ther 2009; 9: 185–191.

    CAS  PubMed  Google Scholar 

  171. Alton EW, Griesenbach U, Geddes DM . Gene therapy for asthma: inspired research or unnecessary effort? Gene Ther 1999; 6: 155–156.

    CAS  PubMed  Google Scholar 

  172. Casanovas M, Martin R, Jimenez C, Caballero R, Fernandez-Caldas E . Safety of immunotherapy with therapeutic vaccines containing depigmented and polymerized allergen extracts. Clin Exp Allergy 2007; 37: 434–440.

    CAS  PubMed  Google Scholar 

  173. Valenta R, Niederberger V . Recombinant allergens for immunotherapy. J Allergy Clin Immunol 2007; 119: 826–830.

    CAS  PubMed  Google Scholar 

  174. Nelson HS . Allergen immunotherapy: where is it now? J Allergy Clin Immunol 2007; 119: 769–779.

    CAS  PubMed  Google Scholar 

  175. Crameri R, Rhyner C . Novel vaccines and adjuvants for allergen-specific immunotherapy. Curr Opin Immunol 2006; 18: 761–768.

    CAS  PubMed  Google Scholar 

  176. Wagner A, Forster-Waldl E, Garner-Spitzer E, Schabussova I, Kundi M, Pollak A et al. Immunoregulation by Toxoplasma gondii infection prevents allergic immune responses in mice. Int J Parasitol 2009; 39: 465–472.

    CAS  PubMed  Google Scholar 

  177. Taher YA, van Esch BC, Hofman GA, Henricks PA, van Oosterhout AJ . 1alpha,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol 2008; 180: 5211–5221.

    CAS  PubMed  Google Scholar 

  178. Hsieh KH . Evaluation of efficacy of traditional Chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study. Taiwan Asthma Study Group. Pediatr Allergy Immunol 1996; 7: 130–140.

    CAS  PubMed  Google Scholar 

  179. Xiang YZ, Shang HC, Gao XM, Zhang BL . A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 2008; 22: 851–858.

    PubMed  Google Scholar 

  180. Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Host A et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007; 62: 943–948.

    CAS  PubMed  Google Scholar 

  181. Canonica GW, Baena-Cagnani CE, Bousquet J, Bousquet PJ, Lockey RF, Malling HJ et al. Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy 2007; 62: 317–324.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology, National Formosa University, Yunlin, Taiwan

    Yi-Ling Ye

  2. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan

    Ya-Hui Chuang

  3. Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan

    Bor-Luen Chiang

Authors
  1. Yi-Ling Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ya-Hui Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bor-Luen Chiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bor-Luen Chiang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ye, YL., Chuang, YH. & Chiang, BL. Strategies of mucosal immunotherapy for allergic diseases. Cell Mol Immunol 8, 453–461 (2011). https://doi.org/10.1038/cmi.2011.17

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2011.17

Keywords

This article is cited by

Search

Advanced search

Quick links