Skip to main content

Novel Vaccines for Type I Allergy

  • Chapter
  • First Online:
Molecular Vaccines

Abstract

Today, type I allergies affect more than 30% of the population in western industrialized countries posing an increasing burden on public health systems. In this book chapter we provide an overview on the molecular characteristics of allergens and the mechanisms of allergic sensitization. Risk factors for sensitization such as genetic predisposition or environmental factors (“hygiene hypothesis”) are discussed and the current standards of diagnosis and medication are summarized. As classical allergen-specific immunotherapy suffers from unwanted side-effects, low patient compliance as well as insufficient efficacy, this chapter focuses on novel therapeutic approaches to overcome these limitations. These include new molecules, such as recombinant (hypo-) allergens or peptides but also advanced vector vaccines, and genetic vaccines. Such vaccine types address specific receptors of the innate immune system, resulting in increased immunogenicity and modulation of unwanted TH2 type responses. Finally, alternative routes to the standard subcutaneous injection or sublingual application are presented, which target highly immunocompetent tissues such as the skin or the lymph nodes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Locksley, R.M.: Asthma and allergic inflammation. Cell 140, 777–783 (2010). doi:10.1016/j.cell.2010.03.004

    Article  PubMed  CAS  Google Scholar 

  2. Mowen, K.A., Glimcher, L.H.: Signaling pathways in Th2 development. Immunol. Rev. 202, 203–222 (2004). doi:10.1111/j.0105-2896.2004.00209.x

    Article  PubMed  CAS  Google Scholar 

  3. Turner, H., Kinet, J.P.: Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature 402, B24–B30 (1999)

    Article  PubMed  CAS  Google Scholar 

  4. Gilles, S., et al.: Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immune systems towards a T(H)2-dominated response. Allergy Asthma Clin. Immunol. 5, 3 (2009). doi:10.1186/1710-1492-5-3

    Article  PubMed  Google Scholar 

  5. Burton, O.T., Zaccone, P.: The potential role of chitin in allergic reactions. Trends Immunol. 28, 419–422 (2007). doi:10.1016/j.it.2007.08.005

    Article  PubMed  CAS  Google Scholar 

  6. Morgenstern, V., et al.: Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children. Am. J. Respir. Crit. Care Med. 177, 1331–1337 (2008). doi:10.1164/rccm.200701-036OC

    Article  PubMed  Google Scholar 

  7. Behrendt, H., Becker, W.M.: Localization, release and bioavailability of pollen allergens: the influence of environmental factors. Curr. Opin. Immunol. 13, 709–715 (2001). doi:S0952-7915(01)00283-7 [pii]

    Article  PubMed  CAS  Google Scholar 

  8. Gruijthuijsen, Y.K., et al.: Nitration enhances the allergenic potential of proteins. Int. Arch. Allergy Immunol. 141, 265–275 (2006). doi:10.1159/000095296

    Article  PubMed  CAS  Google Scholar 

  9. Williams, M.A., et al.: Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J. Immunol. 181, 4545–4559 (2008)

    PubMed  CAS  Google Scholar 

  10. Eisenbarth, S.C., et al.: Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645–1651 (2002)

    Article  PubMed  CAS  Google Scholar 

  11. Herrick, C.A., Bottomly, K.: To respond or not to respond: T cells in allergic asthma. Nat. Rev. Immunol. 3, 405–412 (2003). doi:10.1038/nri1084

    Article  PubMed  CAS  Google Scholar 

  12. Poltorak, A., et al.: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088 (1998)

    Article  PubMed  CAS  Google Scholar 

  13. Shimazu, R., et al.: MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777–1782 (1999)

    Article  PubMed  CAS  Google Scholar 

  14. Furmonaviciene, R., et al.: The protease allergen Der p 1 cleaves cell surface DC-SIGN and DC-SIGNR: experimental analysis of in silico substrate identification and implications in allergic responses. Clin. Exp. Allergy 37, 231–242 (2007). doi:10.1111/j.1365-2222.2007.02651.x

    Article  PubMed  CAS  Google Scholar 

  15. Sokol, C.L., Barton, G.M., Farr, A.G., Medzhitov, R.: A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat. Immunol. 9, 310–318 (2008). doi:10.1038/ni1558

    Article  PubMed  CAS  Google Scholar 

  16. Comeau, M.R., Ziegler, S.F.: The influence of TSLP on the allergic response. Mucosal Immunol. 3, 138–147 (2010). doi:10.1038/mi.2009.134

    Article  PubMed  CAS  Google Scholar 

  17. Trompette, A., et al.: Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009). doi:10.1038/nature07548

    Article  PubMed  CAS  Google Scholar 

  18. van Kooyk, Y.: C-type lectins on dendritic cells: key modulators for the induction of immune responses. Biochem. Soc. Trans. 36, 1478–1481 (2008). doi:10.1042/BST0361478

    Article  PubMed  Google Scholar 

  19. Royer, P.J., et al.: The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity. J. Immunol. 185, 1522–1531 (2010). doi:10.4049/jimmunol.1000774

    Article  PubMed  CAS  Google Scholar 

  20. Kjellman, N.I.: Atopic disease in seven-year-old children. Incidence in relation to family history. Acta Paediatr. Scand. 66, 465–471 (1977)

    Article  PubMed  CAS  Google Scholar 

  21. Marenholz, I., et al.: An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma. J. Allergy Clin. Immunol. 123, 911–916 (2009). doi:10.1016/j.jaci.2009.01.051

    Article  PubMed  CAS  Google Scholar 

  22. Senthilselvan, A., et al.: Association of polymorphisms of toll-like receptor 4 with a reduced prevalence of hay fever and atopy. Ann. Allergy Asthma Immunol. 100, 463–468 (2008). doi:10.1016/S1081-1206(10)60472-3

    Article  PubMed  Google Scholar 

  23. Floistrup, H., et al.: Allergic disease and sensitization in Steiner school children. J. Allergy Clin. Immunol. 117, 59–66 (2006). doi:10.1016/j.jaci.2005.09.039

    Article  PubMed  Google Scholar 

  24. von Mutius, E., Vercelli, D.: Farm living: effects on childhood asthma and allergy. Nat. Rev. Immunol. 10, 861–868 (2010). doi:10.1038/nri2871

    Article  Google Scholar 

  25. Ege, M.J., et al.: Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J. Allergy Clin. Immunol. 117, 817–823 (2006). doi:10.1016/j.jaci.2005.12.1307

    Article  PubMed  Google Scholar 

  26. Riedler, J., et al.: Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129–1133 (2001). doi:10.1016/S0140-6736(01)06252-3

    Article  PubMed  CAS  Google Scholar 

  27. Ege, M.J., et al.: Not all farming environments protect against the development of asthma and wheeze in children. J. Allergy Clin. Immunol. 119, 1140–1147 (2007). doi:10.1016/j.jaci.2007.01.037

    Article  PubMed  Google Scholar 

  28. van Strien, R.T., et al.: Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health. J. Allergy Clin. Immunol. 113, 860–867 (2004). doi:10.1016/j.jaci.2004.01.783

    Article  PubMed  Google Scholar 

  29. Vogel, K., et al.: Animal shed Bacillus licheniformis spores possess allergy-protective as well as inflammatory properties. J. Allergy Clin. Immunol. 122, 307–312, 312 e301–e308 (2008). doi:10.1016/j.jaci.2008.05.016

  30. Lauener, R.P., et al.: Expression of CD14 and Toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet 360, 465–466 (2002). doi:10.1016/S0140-6736(02)09641-1

    Article  PubMed  CAS  Google Scholar 

  31. Pfefferle, P.I., et al.: Cord blood allergen-specific IgE is associated with reduced IFN-gamma production by cord blood cells: the Protection against Allergy-Study in Rural Environments (PASTURE) Study. J. Allergy Clin. Immunol. 122, 711–716 (2008). doi:10.1016/j.jaci.2008.06.035

    Article  PubMed  CAS  Google Scholar 

  32. Romagnani, S.: The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both? Immunology 112, 352–363 (2004). doi:10.1111/j.1365-2567.2004.01925.x

    Article  PubMed  CAS  Google Scholar 

  33. Chang, T.W., Wu, P.C., Hsu, C.L., Hung, A.F.: Anti-IgE antibodies for the treatment of IgE-mediated allergic diseases. Adv. Immunol. 93, 63–119 (2007). doi:10.1016/S0065-2776(06)93002-8

    Article  PubMed  CAS  Google Scholar 

  34. Scheinfeld, N.: Omalizumab: a recombinant humanized monoclonal IgE-blocking antibody. Dermatol. Online J. 11, 2 (2005)

    PubMed  Google Scholar 

  35. Calderon, M., Cardona, V., Demoly, P.: One hundred years of allergen immunotherapy European Academy of Allergy and Clinical Immunology celebration: review of unanswered questions. Allergy 67, 462–476 (2012). doi:10.1111/j.1398-9995.2012.02785.x

    Article  PubMed  CAS  Google Scholar 

  36. Cox, L., Calderon, M.A.: Subcutaneous specific immunotherapy for seasonal allergic rhinitis: a review of treatment practices in the US and Europe. Curr. Med. Res. Opin. 26, 2723–2733 (2010). doi:10.1185/03007995.2010.528647

    Article  PubMed  Google Scholar 

  37. Frew, A.J.: Allergen immunotherapy. J. Allergy Clin. Immunol. 125, S306–S313 (2010). doi:10.1016/j.jaci.2009.10.064

    Article  PubMed  Google Scholar 

  38. Canonica, G.W., et al.: Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy 64(Suppl 91), 1–59 (2009). doi:10.1111/j.1398-9995.2009.02309.x

    PubMed  Google Scholar 

  39. Frew, A.J.: Sublingual immunotherapy. N. Engl. J. Med. 358, 2259–2264 (2008). doi:10.1056/NEJMct0708337

    Article  PubMed  CAS  Google Scholar 

  40. Razafindratsita, A., et al.: Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation. J. Allergy Clin. Immunol. 120, 278–285 (2007). doi:10.1016/j.jaci.2007.04.009

    Article  PubMed  CAS  Google Scholar 

  41. Ball, T., et al.: Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy. Eur. J. Immunol. 29, 2026–2036 (1999). doi:10.1002/(SICI)1521-4141(199906)29:06<2026::AID-IMMU2026>3.0.CO;2-2

    Google Scholar 

  42. Pauli, G., Malling, H.J.: The current state of recombinant allergens for immunotherapy. Curr. Opin. Allergy Clin. Immunol. 10, 575–581 (2010). doi:10.1097/ACI.0b013e32833fd6c5

    Article  PubMed  CAS  Google Scholar 

  43. Bauer, R., et al.: Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy. J. Allergy Clin. Immunol. 118, 269–276 (2006). doi:10.1016/j.jaci.2006.03.033

    Article  PubMed  CAS  Google Scholar 

  44. Purohit, A., et al.: Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin. Exp. Allergy 38, 1514–1525 (2008). doi:10.1111/j.1365-2222.2008.03042.x

    Article  PubMed  CAS  Google Scholar 

  45. Thalhamer, T., et al.: Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening. J. Allergy Clin. Immunol. 125, 926–934, e910 (2010). doi:10.1016/j.jaci.2010.01.031

  46. Haselden, B.M., Kay, A.B., Larche, M.: Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J. Exp. Med. 189, 1885–1894 (1999)

    Article  PubMed  CAS  Google Scholar 

  47. Albrecht, M., et al.: Vaccination with a Modified Vaccinia Virus Ankara-based vaccine protects mice from allergic sensitization. J. Gene Med. 10, 1324–1333 (2008). doi:10.1002/jgm.1256

    Article  PubMed  CAS  Google Scholar 

  48. Kumar, M., Behera, A.K., Matsuse, H., Lockey, R.F., Mohapatra, S.S.: A recombinant BCG vaccine generates a Th1-like response and inhibits IgE synthesis in BALB/c mice. Immunology 97, 515–521 (1999)

    Article  PubMed  CAS  Google Scholar 

  49. Rigaux, P., et al.: Immunomodulatory properties of Lactobacillus plantarum and its use as a recombinant vaccine against mite allergy. Allergy 64, 406–414 (2009). doi:10.1111/j.1398-9995.2008.01825.x

    Article  PubMed  CAS  Google Scholar 

  50. Schmitz, N., et al.: Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy. J. Exp. Med. 206, 1941–1955 (2009). doi:10.1084/jem.20090199

    Article  PubMed  CAS  Google Scholar 

  51. Weiss, R., et al.: Is genetic vaccination against allergy possible? Int. Arch. Allergy Immunol. 139, 332–345 (2006). doi:10.1159/000091946

    Article  PubMed  CAS  Google Scholar 

  52. Roesler, E., et al.: Immunize and disappear-safety-optimized mRNA vaccination with a panel of 29 allergens. J. Allergy Clin. Immunol. 124, 1070–1077, e1071-1011, doi:10.1016/j.jaci.2009.06.036 (2009).

  53. Weiss, R., Scheiblhofer, S., Roesler, E., Weinberger, E., Thalhamer, J.: mRNA vaccination as a safe approach for specific protection from type I allergy. Expert Rev. Vaccines 11, 55–67 (2012). doi:10.1586/erv.11.168

    Article  PubMed  CAS  Google Scholar 

  54. Gabler, M., et al.: Immunization with a low-dose replicon DNA vaccine encoding Phl p 5 effectively prevents allergic sensitization. J. Allergy Clin. Immunol. 118, 734–741 (2006). doi:10.1016/j.jaci.2006.04.048. S0091-6749(06)00943-2 [pii]

    Article  PubMed  CAS  Google Scholar 

  55. Scheiblhofer, S., et al.: Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines. Allergy 61, 828–835 (2006). doi:10.1111/j.1398-9995.2006.01142.x. ALL1142 [pii]

    Article  PubMed  CAS  Google Scholar 

  56. Leitner, W.W., Bergmann-Leitner, E.S., Hwang, L.N., Restifo, N.P.: Type I Interferons are essential for the efficacy of replicase-based DNA vaccines. Vaccine 24, 5110–5118 (2006). doi:10.1016/j.vaccine.2006.04.059

    Article  PubMed  CAS  Google Scholar 

  57. Eifan, A.O., Shamji, M.H., Durham, S.R.: Long-term clinical and immunological effects of allergen immunotherapy. Curr. Opin. Allergy Clin. Immunol. 11, 586–593 (2011). doi:10.1097/ACI.0b013e32834cb994

    Article  PubMed  CAS  Google Scholar 

  58. Bal, S.M., Ding, Z., Jiskoot, W., Bouwstra, J.A.: Advances in transcutaneous vaccine delivery: do all ways lead to Rome? J. Control. Release 148, 266–282 (2010). doi:10.1016/j.jconrel.2010.09.018

    Article  PubMed  CAS  Google Scholar 

  59. Gutowska-Owsiak, D., Ogg, G.S.: The epidermis as an adjuvant. J. Invest. Dermatol. 132, 940–948 (2012). doi:10.1038/jid.2011.398

    Article  PubMed  CAS  Google Scholar 

  60. Blamoutier, P., Blamoutier, J., Guibert, L.: Treatment of pollinosis with pollen extracts by the method of cutaneous quadrille ruling. Presse Med. 67, 2299–2301 (1959)

    PubMed  CAS  Google Scholar 

  61. Senti, G., et al.: Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J. Allergy Clin. Immunol. 124, 997–1002 (2009). doi:10.1016/j.jaci.2009.07.019

    Article  PubMed  CAS  Google Scholar 

  62. Senti, G., et al.: Epicutaneous allergen-specific immunotherapy ameliorates grass pollen-induced rhinoconjunctivitis: a double-blind, placebo-controlled dose escalation study. J. Allergy Clin. Immunol. 129, 128–135 (2012). doi:10.1016/j.jaci.2011.08.036

    Article  PubMed  CAS  Google Scholar 

  63. Dupont, C., et al.: Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J. Allergy Clin. Immunol. 125, 1165–1167 (2010). doi:10.1016/j.jaci.2010.02.029

    Article  PubMed  CAS  Google Scholar 

  64. Weiss, R., et al.: Transcutaneous vaccination via laser microporation. J. Control. Release (2012). doi:10.1016/j.jconrel.2012.06.031

  65. Bach, D., et al.: Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5-sensitized mice. Allergy (2012). doi:10.1111/all.12005

  66. Senti, G., et al.: Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J. Allergy Clin. Immunol. 129, 1290–1296 (2012). doi:10.1016/j.jaci.2012.02.026

    Article  PubMed  CAS  Google Scholar 

  67. Senti, G., et al.: Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc. Natl. Acad. Sci. U. S. A. 105, 17908–17912 (2008). doi:10.1073/pnas.0803725105

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Weiss PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Scheiblhofer, S., Thalhamer, J., Weiss, R. (2014). Novel Vaccines for Type I Allergy. In: Giese, M. (eds) Molecular Vaccines. Springer, Cham. https://doi.org/10.1007/978-3-319-00978-0_4

Download citation

Publish with us

Policies and ethics