Skip to main content
SpringerLink
Log in

Engineering Allergy Vaccines: Approaches Towards Engineered Allergy Vaccines

  • Chapter
Allergy Frontiers: Future Perspectives

Part of the book series: Allergy Frontiers ((ALLERGY,volume 6))

  • 629 Accesses

Abstract

The basic principle of allergen specific immunotherapy conducted by subcutaneous injection is the administration of increasing doses of allergen up to a maintenance dose or a maximum tolerated dose to ameliorate IgE antibody mediated allergic inflammation and associated symptoms, and reduce the need for symptomatic medication. The magnitude of the dose is apparently important in ensuring the success of treatment. Whereas low allergen doses favor a Th2 cytokine response and a switch to IgE, high allergen doses favor induction of regulatory T-cells and modification or down-regulation of the Th2 phenotype [1]. However the administration of high doses in man carries an increased risk for the induction of undesirable side-effects, and at worst life-threatening anaphylactic reactions which are a logical risk with a causal treatment.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Larche M, Akdis CA, Valenta R (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6:761–71

    Article  PubMed  CAS  Google Scholar 

  2. Maasch HJ, Marsh DG (1987) Standardized extracts: Modified allergens — Allergoids. Clin Rev Allergy 5:89–106

    PubMed  CAS  Google Scholar 

  3. Akdis CA, Blaser K (2001) Bypassing IgE and targeting T cells for specific immunotherapy of allergy. Trends Immunol 22:175–8

    Article  PubMed  CAS  Google Scholar 

  4. Cirkovic TD, Bukilica MN, Gavrovic MD et al (1999) Physicochemical and immunologic characterization of low molecular- weight allergoids of Dactylis glomerata pollen proteins. Allergy 54:128–34

    Article  PubMed  CAS  Google Scholar 

  5. Mistrello G, Brenna O, Roncarolo D et al (1996) Monomeric chemically modified allergens: Immunologic and physicochemical characterization. Allergy 51:8–15

    PubMed  CAS  Google Scholar 

  6. Rappuoli R, Douce G, Dougan G, et al (1995) Genetic detoxification of bacterial toxins: a new approach to vaccine development. [Review]. Int Arch Allergy Immunol 108:327–33

    Article  PubMed  CAS  Google Scholar 

  7. Spangfort MD, Mirza O, Ipsen H, et al (2003) Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed muta-genesis. J Immunol 171:3084–90

    PubMed  CAS  Google Scholar 

  8. Breiteneder H, Mills EN (2005) Molecular properties of food allergens. J Allergy Clin Immunol 115:14–23

    Article  PubMed  CAS  Google Scholar 

  9. Stadler MB, Stadler BM (2003) Allergenicity prediction by protein sequence. FASEB J 17:1141–3

    PubMed  CAS  Google Scholar 

  10. Furmonaviciene R, Sewell HF, Shakib F (2000) Comparative molecular modelling identifies a common putative IgE epitope on cysteine protease allergens of diverse sources. Clin Exp Allergy 30:1307–13

    Article  PubMed  CAS  Google Scholar 

  11. Arquint O, Helbling A, Crameri R, et al (1999) Reduced in vivo allergenicity of Bet v 1d isoform, a natural component of birch pollen. J Allergy Clin Immunol 104:1239–43

    Article  PubMed  CAS  Google Scholar 

  12. Ferreira F, Ebner C, Kramer B, et al (1998) Modulation of IgE reactivity of allergens by site-directed mutagenesis: Potential use of hypoallergenic variants for immunotherapy. FASEB J 12:231–42

    PubMed  CAS  Google Scholar 

  13. Holm J, Gajhede M, Ferreras M (2004) Allergy vaccine engineering: Epitope modulation of recombinant Bet v 1 reduces IgE binding but retains protein folding pattern for induction of protective blocking-antibody responses. J Immunol 173:5258–67

    PubMed  CAS  Google Scholar 

  14. Rabjohn P, West CM, Connaughton C (2002) Modification of peanut allergen Ara h 3: Effects on IgE binding and T cell stimulation. Int Arch Allergy Immunol 128:15–23

    Article  PubMed  CAS  Google Scholar 

  15. Swoboda I, Bugajska-Schretter A, et al (2007) A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol 178:6290–6

    PubMed  CAS  Google Scholar 

  16. Haselden BM, Kay AB, Larche M (1999) Immunoglobulin E-independent major histocom-patibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med 189:1885–94

    Article  PubMed  CAS  Google Scholar 

  17. Kay AB, Larche M (2004) Allergen immunotherapy with cat allergen peptides. Springer Semin Immunopathol 25:391–9

    Article  PubMed  Google Scholar 

  18. Verhoef A, Alexander C, Kay AB, et al (2005) T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med 2:e78

    Article  PubMed  CAS  Google Scholar 

  19. Vrtala S, Hirtenlehner K, Vangelista L (1997) Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments – Candidates for a novel form of specific immunotherapy. J Clin Invest 99:1673–81

    Article  PubMed  CAS  Google Scholar 

  20. van Hage-Hamsten M, Kronqvist M, Zetterström O (1999) Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1: Results obtained with a mix of two recombinant Bet v 1 fragments and recombinant Bet v 1 trimer in a Swedish population before the birch pollen season. J Allergy Clin Immunol 104:969–77

    Article  PubMed  Google Scholar 

  21. Vrtala S, Focke M, Sperr W, et al (2001) Recombinant hypoallergenic fragments of the major Timothy grass pollen allergen, Phl p 6, for immunotherapy. J Allergy Clin Immunol 107:S257

    Google Scholar 

  22. Kinnunen T, Buhot C, Narvanen A (2003) The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells. Eur J Immunol 33:1717–26

    Article  PubMed  CAS  Google Scholar 

  23. Kinnunen T, Jutila K, Kwok WW, et al (2007) Potential of an altered peptide ligand of lipoc-alin allergen Bos d 2 for peptide immunotherapy. J Allergy Clin Immunol 119:965–72

    Article  PubMed  CAS  Google Scholar 

  24. Linhart B, Valenta R (2004) Vaccine Engineering Improved by Hybrid Technology. Int Arch Allergy Immunol 134:324–31

    Article  PubMed  CAS  Google Scholar 

  25. Hirahara K, Tatsuta T, Takatori T, et al (2001). Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens. J Allergy Clin Immunol 108:94–100

    Article  PubMed  CAS  Google Scholar 

  26. Karamloo F, Schmid-Grendelmeier P, Kussebi F (2005) Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes. Eur J Immunol 35:3268–76

    Article  PubMed  CAS  Google Scholar 

  27. Punnonen J (2000) Molecular breeding of allergy vaccines and antiallergic cytokines. Int Arch Allergy Immunol 121:173–82

    Article  PubMed  CAS  Google Scholar 

  28. Ferreira F, Wallner M, Breiteneder H et al (2002) Genetic engineering of allergens: Future therapeutic products. Int Arch Allergy Immunol 128:171–8

    Article  PubMed  CAS  Google Scholar 

  29. Gafvelin G, Parmley S, Neimert-Andersson T, et al (2007) Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens. J Biol Chem 282:3778–87

    Article  PubMed  CAS  Google Scholar 

  30. Wild C, Wallner M, Hufnagl K, et al (2007) A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities. Allergy 62:33–41

    Article  PubMed  CAS  Google Scholar 

  31. Vrtala S, Hirtenlehner K, Susani M et al (2001) Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen, Bet v 1. FASEB J 15:2045–7

    PubMed  CAS  Google Scholar 

  32. Pauli G, Purohit A, Oster JP, et al (2000) Comparison of genetically engineered hypoaller-genic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: Results obtained in a French population. Clin Exp Allergy 30:1076–84

    Article  PubMed  CAS  Google Scholar 

  33. Kahlert H, Weber B, Cromwell O, et al (2003) Evaluation of the allergenicity of hypoaller-genic recombinant derivatives of Bet v 1 using basophil activation by CD203c expression measurement. In: Marone G, editor. Clinical Immunology and Allergy in Medicine. Naples, Italy: JGC Editions, 735–40

    Google Scholar 

  34. Niederberger V, Horak F, Vrtala S, et al (2004) Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci USA 101(Suppl 2):14677–82

    Article  PubMed  CAS  Google Scholar 

  35. Reese G, Ballmer-Weber BK, Wangorsch A, et al (2007) Allergenicity and antigenicity of wild-type and mutant, monomeric, and dimeric carrot major allergen Dau c 1: Destruction of conformation, not oligomerization, is the roadmap to save allergen vaccines. J Allergy Clin Immunol 119:944–51

    Article  PubMed  CAS  Google Scholar 

  36. Linhart B, Hartl A, Jahn-Schmid B, et al (2005) A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination. J Allergy Clin Immunol 115:1010–6

    Article  PubMed  CAS  Google Scholar 

  37. Ma Y, Gadermaier G, Bohle B et al (2006) Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1. Int Arch Allergy Immunol 139:53–62

    Article  PubMed  CAS  Google Scholar 

  38. Son DY, Scheurer S, Hoffmann A, et al (1999) Pollen-related food allergy: Cloning and immunological analysis of isoforms and mutants of Mal d 1, the major apple allergen, and Bet v 1, the major birch pollen allergen. Eur J Nutr 38:201–15

    Article  PubMed  CAS  Google Scholar 

  39. Westritschnig K, Focke M, Verdino P, et al (2004) Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7. J Immunol 172:5684–92

    PubMed  CAS  Google Scholar 

  40. Smith AM, Chapman MD (1996) Reduction in IgE binding to allergen variants generated by site- directed mutagenesis: Contribution of disulfide bonds to the antigenic structure of the major house dust mite allergen Der p 2. Mol Immunol 33:399–405

    Article  PubMed  CAS  Google Scholar 

  41. Takai T, Yokota T, Yasue M, et al (1997) Engineering of the major house dust mite allergen Der f2 for allergen-specific immunotherapy. Nat Biotechnol 15:754–8

    Article  PubMed  CAS  Google Scholar 

  42. Olsson S, van Hage-Hamsten M, Whitley P (1998) Contribution of disulphide bonds to anti-genicity of Lep d 2, the major allergen of the dust mite Lepidoglyphus destructor. Mol Immunol 35:1017–23

    Article  PubMed  CAS  Google Scholar 

  43. Bonura A, Amoroso S, Locorotondo G, et al (2001) Hypoallergenic variants of the Parietaria judaica major allergen Par j 1: A member of the non-specific lipid transfer protein plant family. Int Arch Allergy Immunol 126:32–40

    Article  PubMed  CAS  Google Scholar 

  44. Drew AC, Eusebius NP, Kenins L, et al (2004) Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol 173:5872–9

    PubMed  CAS  Google Scholar 

  45. Korematsu S, Tanaka Y, Hosoi S, et al (2000) C8/119S mutation of major mite allergen Derf-2 leads to degenerate secondary structure and molecular polymerization and induces potent and exclusive Th1 cell differentiation. J Immunol 165:2895–902

    PubMed  CAS  Google Scholar 

  46. Kauppinen J, Zeiler T, Rautiainen J, et al (1999) Mutant derivatives of the main respiratory allergen of cow are less allergenic than the intact molecule. Clin Exp Allergy 29:989–96

    Article  PubMed  CAS  Google Scholar 

  47. Takai T, Ichikawa S, Yokota T, et al (2000) Unlocking the allergenic structure of the major house dust mite allergen der f 2 by elimination of key intramolecular interactions. FEBS Lett 484:102–7

    Article  PubMed  CAS  Google Scholar 

  48. Swoboda I, de Weerd N, Bhalla PL, et al (2002) Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: Candidates for grass pollen-specific immuno-therapy. Eur J Immunol 32:270–80

    Article  PubMed  CAS  Google Scholar 

  49. Schramm G, Kahlert H, Suck R, et al (1999) “Allergen engineering”: Variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity. J Immunol 162:2406–14

    PubMed  CAS  Google Scholar 

  50. Wald M, Kahlert H, Weber B, et al (2007) Generation of a low Immunoglobulin E-binding mutant of the timothy grass pollen major allergen Phl p 5a. Clin Exp Allergy 37:441–50

    Article  PubMed  CAS  Google Scholar 

  51. Marazuela EG, Rodriguez R, Barber D, et al (2007) Hypoallergenic mutants of Ole e 1, the major olive pollen allergen, as candidates for allergy vaccines. Clin Exp Allergy 37:251–60

    Article  PubMed  CAS  Google Scholar 

  52. Garcia-Ortega L, Lacadena J, Villalba M, et al (2005) Production and characterization of a noncytotoxic deletion variant of the Aspergillus fumigatus allergen Aspf1 displaying reduced IgE binding. FEBS J 272:2536–44

    Article  PubMed  CAS  Google Scholar 

  53. Reisinger J, Horak F, Pauli G, et al (2005) Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 116:347–54

    Article  PubMed  CAS  Google Scholar 

  54. Gafvelin G, Thunberg S, Kronqvist M, et al (2005) Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1. Int Arch Allergy Immunol 138:59–66

    Article  PubMed  CAS  Google Scholar 

  55. Weber B, Slamal H, Suck R (2003) Size exclusion chromatography as a tool for quality control of recombinant allergens and hypoallergenic variants. J Biochem Biophys Methods 56:219–32

    Article  PubMed  CAS  Google Scholar 

  56. Kettner J, Meyer H, Cromwell O, et al (2007) Specific immunotherapy with recombinant birch pollen allergen rBet v1-FV results of 2 years of treatment (Phase II trial). Allergy 62(Suppl 83):262

    Google Scholar 

  57. Kettner J, Meyer H, Narkus A, et al (2007) Specific immunotherapy with recombinant birch pollen allergen rBet v 1-FV is clinically efficacious — results of a Phase III study. Allergy 62(Suppl 83):33

    Google Scholar 

  58. Tighe H, Takabayashi K, Schwartz D, et al (2000) Conjugation of immunostimulatory DNA to the short ragweed allergen Amb a 1 enhances its immunogenicity and reduces its allerge-nicity. J Allergy Clin Immunol 106:124–34

    Article  PubMed  CAS  Google Scholar 

  59. Crameri R, Fluckiger S, Daigle I, et al (2007) Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines. Allergy 62:197–206

    Article  PubMed  CAS  Google Scholar 

  60. Zhu D, Kepley CL, Zhang M, et al (2002) A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epsilon RI-mediated degranulation. Nat Med 8:518–21

    Article  PubMed  CAS  Google Scholar 

  61. Zhu D, Kepley CL, Zhang K, et al (2005) A chimeric human—cat fusion protein blocks cat-induced allergy. Nat Med 11:446–9

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergopharma J. Ganzer KG, Hermann-Koerner-Str. 52, Reinbek, 21465, Germany

    Oliver Cromwell

Authors
  1. Oliver Cromwell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oliver Cromwell .

Editor information

Editors and Affiliations

  1. Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan

    Ruby Pawankar

  2. University of Southampton Southampton General Hospital, Tremona Road, Southampton, UK

    Stephen T. Holgate

  3. Children's Mercy Hospitals and Clinics UMKC School of Medicine, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Lanny J. Rosenwasser

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer

About this chapter

Cite this chapter

Cromwell, O. (2010). Engineering Allergy Vaccines: Approaches Towards Engineered Allergy Vaccines. In: Pawankar, R., Holgate, S.T., Rosenwasser, L.J. (eds) Allergy Frontiers: Future Perspectives. Allergy Frontiers, vol 6. Springer, Tokyo. https://doi.org/10.1007/978-4-431-99365-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-99365-0_3

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-99364-3

  • Online ISBN: 978-4-431-99365-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation