Table of Contents Author Guidelines Submit a Manuscript
Clinical and Developmental Immunology
Volume 2012, Article ID 623474, 8 pages
http://dx.doi.org/10.1155/2012/623474
Review Article

Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

Département Scientifique, Stallergènes SA, 6 rue Alexis de Tocqueville, 92160 Antony, France

Received 30 May 2011; Accepted 23 September 2011

Academic Editor: Donna-Marie McCafferty

Copyright © 2012 Philippe Moingeon and Laurent Mascarell. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Noon, “Prophylactic inoculation against hay fever,” The Lancet, vol. 177, no. 4580, pp. 1572–1573, 1911. View at Google Scholar · View at Scopus
  2. J. Freeman, “Further observations on the treatment of hay fever by hypodermic inoculations of pollen vaccine,” The Lancet, vol. 178, no. 4594, pp. 814–817, 1911. View at Google Scholar · View at Scopus
  3. J. Bousquet, R. Lockey, H. J. Malling et al., “Allergen immunotherapy: therapeutic vaccines for allergic diseases—a WHO position paper,” Journal of Allergy and Clinical Immunology, vol. 102, no. 4, pp. 558–562, 1998. View at Google Scholar · View at Scopus
  4. L. Cox, J. T. Li, H. Nelson, and R. Lockey, “Allergen immunotherapy: a practice parameter second update,” Journal of Allergy and Clinical Immunology, vol. 120, no. 3, pp. S25–S85, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. G. W. Canonica and G. Passalacqua, “Noninjection routes for immunotherapy,” Journal of Allergy and Clinical Immunology, vol. 111, no. 3, pp. 437–448, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. G. W. Canonica, J. Bousquet, T. Casale et al., “Sub-lingual immunotherapy: world allergy organization position paper 2009,” Allergy, vol. 64, no. 91, pp. 1–59, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. G. Passalacqua, C. Lombardi, C. Troise, and G. W. Canonica, “Sublingual immunotherapy: certainties, unmet needs and future directions,” European Annals of Allergy and Clinical Immunology, vol. 41, no. 6, pp. 163–170, 2009. View at Google Scholar · View at Scopus
  8. A. J. Frew, “How does sublingual immunotherapy work?” Journal of Allergy and Clinical Immunology, vol. 120, no. 3, pp. 533–536, 2007. View at Publisher · View at Google Scholar · View at PubMed
  9. L. Mayer and L. Shao, “Therapeutic potential of oral tolerance,” Nature Reviews Immunology, vol. 4, no. 6, pp. 407–419, 2004. View at Google Scholar · View at Scopus
  10. A. M. I. Mowat, L. A. Parker, H. Beacock-Sharp, O. R. Millington, and F. Chirdo, “Oral tolerance: overview and historical perspectives,” Annals of the New York Academy of Sciences, vol. 1029, pp. 1–8, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. A. M. C. Faria and H. L. Weiner, “Oral tolerance,” Immunological Reviews, vol. 206, pp. 232–259, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. R. Urbanek, K. H. Burgelin, S. Kahle, W. Kuhn, and U. Wahn, “Oral immunotherapy with grass pollen in enterosoluble capsules. A prospective study of the clinical and immunological response,” European Journal of Pediatrics, vol. 149, no. 8, pp. 545–550, 1990. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Moller, S. Dreborg, A. Lanner, and B. Bjorksten, “Oral immunotherapy of children with rhinoconjunctivitis due to birch pollen allergy. A double blind study,” Allergy, vol. 41, no. 4, pp. 271–279, 1986. View at Google Scholar · View at Scopus
  14. E. Taudorf, L. C. Laursen, and A. Lanner, “Oral immunotherapy in birch pollen hay fever,” Journal of Allergy and Clinical Immunology, vol. 80, no. 2, pp. 153–161, 1987. View at Google Scholar
  15. H. Deuschl and S. G. O. Johansson, “Hyposensitization of patients with allergic rhinitis by intranasal administration of chemically modified grass pollen allergen. A pilot study,” Acta Allergologica, vol. 32, no. 4, pp. 248–262, 1977. View at Google Scholar · View at Scopus
  16. J. A. Nickelsen, S. Goldstein, and U. Mueller, “Local intranasal immunotherapy for ragweed allergic rhinitis. I. Clinical response,” Journal of Allergy and Clinical Immunology, vol. 68, no. 1, pp. 33–40, 1981. View at Google Scholar
  17. J. W. Georgitis, R. E. Reisman, and W. F. Clayton, “Local intranasal immunotherapy for grass-allergic rhinitis,” Journal of Allergy and Clinical Immunology, vol. 71, no. 1 I, pp. 71–76, 1983. View at Google Scholar
  18. G. Senti, A. U. Freiburghaus, and T. M. Kundig, “Epicutaneous/transcutaneous allergen-specific immunotherapy: rationale and clinical trials,” Current Opinion in Allergy and Clinical Immunology, vol. 10, no. 6, pp. 582–586, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. V. Dioszeghy, L. Mondoulet, V. Dhelft et al., “Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice,” Journal of Immunology, vol. 186, no. 10, pp. 5629–5637, 2011. View at Publisher · View at Google Scholar · View at PubMed
  20. G. Senti, B. M. Prinz Vavricka, I. Erdmann et al., “Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 46, pp. 17908–17912, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. P. Moingeon, T. Batard, R. Fadel, F. Frati, J. Sieber, and L. van Overtvelt, “Immune mechanisms of allergen-specific sublingual immunotherapy,” Allergy, vol. 61, no. 2, pp. 151–165, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. P. Moingeon, “Sublingual immunotherapy: from biological extracts to recombinant allergens,” Allergy, vol. 61, no. 81, pp. 15–19, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. D. R. Wilson, M. T. Lima, and S. R. Durham, “Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis,” Allergy, vol. 60, no. 1, pp. 4–12, 2005. View at Google Scholar · View at Scopus
  24. Z. Calamita, H. Saconato, A. B. Pelá, and A. N. Atallah, “Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method,” Allergy, vol. 61, no. 10, pp. 1162–1172, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. M. Penagos, G. Passalacqua, E. Compalati et al., “Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age,” Chest, vol. 133, no. 3, pp. 599–609, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. M. Penagos, E. Compalati, F. Tarantini et al., “Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials,” Annals of Allergy, Asthma and Immunology, vol. 97, no. 2, pp. 141–148, 2006. View at Google Scholar · View at Scopus
  27. A. Pipet, K. Botturi, D. Pinot, D. Vervloet, and A. Magnan, “Allergen-specific immunotherapy in allergic rhinitis and asthma. Mechanisms and proof of efficacy,” Respiratory Medicine, vol. 103, no. 6, pp. 800–812, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. R. Dahl, A. Kapp, G. Colombo et al., “Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis,” Journal of Allergy and Clinical Immunology, vol. 118, no. 2, pp. 434–440, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. Didier, H. J. Malling, M. Worm et al., “Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis,” Journal of Allergy and Clinical Immunology, vol. 120, no. 6, pp. 1338–1345, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. T. Batard, A. Hrabina, Z. B. Xue et al., “Production and proteomic characterization of pharmaceutical-grade Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts for allergy vaccines,” International Archives of Allergy and Immunology, vol. 140, no. 4, pp. 295–305, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. M. Marogna, I. Spadolini, A. Massolo, G. W. Canonica, and G. Passalacqua, “Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study,” Journal of Allergy and Clinical Immunology, vol. 126, no. 5, pp. 969–975, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. S. R. Durham, W. Emminger, A. Kapp et al., “Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet,” Journal of Allergy and Clinical Immunology, vol. 125, no. 1–3, pp. 131–138, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. L. Mascarell, V. Lombardi, A. Louise et al., “Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells,” Journal of Allergy and Clinical Immunology, vol. 122, no. 3, pp. 603–609, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. L. Mascarell, V. Lombardi, A. Zimmer et al., “Mapping of the lingual immune system reveals the presence of both regulatory and effector CD4+ T cells,” Clinical and Experimental Allergy, vol. 39, no. 12, pp. 1910–1919, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. N. Novak, J. Haberstok, T. Bieber, and J. P. Allam, “The immune privilege of the oral mucosa,” Trends in Molecular Medicine, vol. 14, no. 5, pp. 191–198, 2008. View at Publisher · View at Google Scholar · View at PubMed
  36. J. P. Allam, P. A. Würtzen, M. Reinartz 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-β1 and IL-10-producing properties,” Journal of Allergy and Clinical Immunology, vol. 126, no. 3, pp. 638–645, 2010. View at Publisher · View at Google Scholar · View at PubMed
  37. J.-P. Allam, N. Novak, C. Fuchs et al., “Characterization of dendritic cells from human oral mucosa: a new Langerhans' cell type with high constitutive FcεRI expression,” Journal of Allergy and Clinical Immunology, vol. 112, no. 1, pp. 141–148, 2003. View at Publisher · View at Google Scholar
  38. J. P. Allam, G. Stojanovski, N. Friedrichs et al., “Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy?” Allergy, vol. 63, no. 6, pp. 720–727, 2008. View at Publisher · View at Google Scholar · View at PubMed
  39. L. Mascarell, N. Saint Lu, H. Moussu et al., “A role for oral macrophage-like cells in establishing tolerance following sublingual immunization,” Mucosal Immunology. In press.
  40. C. Czerkinsky, N. Çuburu, M.-N. Kweon, F. Anjuere, and J. Holmgren, “Sublingual vaccination,” Human Vaccines, vol. 7, no. 1, pp. 110–114, 2011. View at Publisher · View at Google Scholar
  41. M. Larché, C. A. Akdis, and R. Valenta, “Immunological mechanisms of allergen-specific immunotherapy,” Nature Reviews Immunology, vol. 6, no. 10, pp. 761–771, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. M. Jutel, M. Akdis, K. Blaser, and C. A. Akdis, “Mechanisms of allergen specific immunotherapy—t-cell tolerance and more,” Allergy, vol. 61, no. 7, pp. 796–807, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. G. Scadding and S. Durham, “Mechanisms of sublingual immunotherapy,” Journal of Asthma, vol. 46, no. 4, pp. 322–334, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. R. J. J. van Neerven, T. Wikborg, G. Lund et al., “Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation,” Journal of Immunology, vol. 163, no. 5, pp. 2944–2952, 1999. View at Google Scholar
  45. P. A. Wachholz and S. R. Durham, “Induction of “blocking” IgG antibodies during immunotherapy,” Clinical and Experimental Allergy, vol. 33, no. 9, pp. 1171–1174, 2003. View at Publisher · View at Google Scholar
  46. N. N. Bahceciler, C. Arikan, A. Taylor et al., “Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites,” International Archives of Allergy and Immunology, vol. 136, no. 3, pp. 287–294, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. A. Razafindratsita, N. Saint-Lu, L. Mascarell et al., “Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation,” Journal of Allergy and Clinical Immunology, vol. 120, no. 2, pp. 278–285, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. S. R. Durham, V. A. Varney, M. Gaga et al., “Grass pollen immunotherapy decreases the number of mast cells in the skin,” Clinical and Experimental Allergy, vol. 29, no. 11, pp. 1490–1496, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. D. R. Wilson, A. M. Irani, S. M. Walker et al., “Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium,” Clinical and Experimental Allergy, vol. 31, no. 11, pp. 1705–1713, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. O. Iliopoulos, D. Proud, N. F. Adkinson et al., “Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells,” Journal of Allergy and Clinical Immunology, vol. 87, no. 4, pp. 855–866, 1991. View at Google Scholar · View at Scopus
  51. G. Ciprandi, D. Fenoglio, I. Cirillo et al., “Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report,” Annals of Allergy, Asthma and Immunology, vol. 95, no. 1, pp. 38–44, 2005. View at Google Scholar · View at Scopus
  52. B. Bohle, T. Kinaciyan, M. Gerstmayr, A. Radakovics, B. Jahn-Schmid, and C. Ebner, “Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation,” Journal of Allergy and Clinical Immunology, vol. 120, no. 3, pp. 707–713, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. R. Valenta, “The future of antigen-specific immunotherapy of allergy,” Nature Reviews Immunology, vol. 2, no. 6, pp. 446–453, 2002. View at Google Scholar · View at Scopus
  54. T. Batard, A. Didierlaurent, H. Chabre et al., “Characterization of wild-type recombinant Bet v 1a as a candidate vaccine against birch pollen allergy,” International Archives of Allergy and Immunology, vol. 136, no. 3, pp. 239–249, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. G. Pauli, T. H. Larsen, S. Rak et al., “Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis,” Journal of Allergy and Clinical Immunology, vol. 122, no. 5, pp. 951–960, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. D. Larenas-Linnemann, “Oralair Birch, a recombinant major birch pollen allergen tablet for sublingual immunotherapy of allergic rhinitis caused by birch pollen,” Current Opinion in Investigational Drugs, vol. 11, no. 5, pp. 586–596, 2010. View at Google Scholar · View at Scopus
  57. P. Moingeon, V. Lombardi, N. Saint-Lu, S. Tourdot, V. Bodo, and L. Mascarell, “Adjuvants and vector systems for allergy vaccines,” Immunology and Allergy Clinics of North America, vol. 31, no. 2, pp. 407–419, 2011. View at Publisher · View at Google Scholar · View at PubMed
  58. L. Mascarell, L. van Overtvelt, V. Lombardi et al., “A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune responses and enhances tolerance induction via the sublingual route,” Vaccine, vol. 26, no. 1, pp. 108–118, 2007. View at Publisher · View at Google Scholar · View at PubMed
  59. V. Lombardi, L. van Overtvelt, S. Horiot et al., “Toll-like receptor 2 agonist Pam3CSK4 enhances the induction of antigen-specific tolerance via the sublingual route,” Clinical and Experimental Allergy, vol. 38, no. 11, pp. 1819–1829, 2008. View at Publisher · View at Google Scholar · View at PubMed
  60. L. van Overtvelt, V. Lombardi, A. Razafindratsita et al., “IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model,” International Archives of Allergy and Immunology, vol. 145, no. 2, pp. 152–162, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. L. van Overtvelt, H. Moussu, S. Horiot et al., “Lactic acid bacteria as adjuvants for sublingual allergy vaccines,” Vaccine, vol. 28, no. 17, pp. 2986–2992, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. O. Pfaar, C. Barth, C. Jaschke, K. Hörmann, and L. Klimek, “Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study,” International Archives of Allergy and Immunology, vol. 154, no. 4, pp. 336–344, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. N. Saint-Lu, S. Tourdot, A. Razafindratsita et al., “Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance induction,” Allergy, vol. 64, no. 7, pp. 1003–1013, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. C. Möller, S. Dreborg, H. A. Ferdousi et al., “Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-Study),” Journal of Allergy and Clinical Immunology, vol. 109, no. 2, pp. 251–256, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Bousquet, P. Scheinmann, M. T. Guinnepain et al., “Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study,” Allergy, vol. 54, no. 3, pp. 249–260, 1999. View at Publisher · View at Google Scholar · View at Scopus
  66. G. B. Pajno, L. Morabito, G. Barberio, and S. Parmiani, “Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study,” Allergy, vol. 55, no. 9, pp. 842–849, 2000. View at Publisher · View at Google Scholar · View at Scopus
  67. G. Passalacqua, E. Compalati, and G. W. Canonica, “Sublingual Immunotherapy: other Indications,” Immunology and Allergy Clinics of North America, vol. 31, no. 2, pp. 279–287, 2011. View at Publisher · View at Google Scholar · View at PubMed
  68. M. Fernández-Rivas, S. Garrido Fernández, J. A. Nadal et al., “Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract,” Allergy, vol. 64, no. 6, pp. 876–883, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. E. Enrique, F. Pineda, T. Malek et al., “Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract,” Journal of Allergy and Clinical Immunology, vol. 116, no. 5, pp. 1073–1079, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. G. B. Pajno, L. Caminiti, D. Vita et al., “Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study,” Journal of Allergy and Clinical Immunology, vol. 120, no. 1, pp. 164–170, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus