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Clinical Experience with Recombinant Molecules for Allergy Vaccination

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Vaccines against Allergies

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 352))

Abstract

Numerous allergens have been cloned and produced by the use of recombinant DNA technology. In several cases recombinant variants with reduced IgE-reactivity have also been developed as candidates for allergen specific immunotherapy. Only very few of these proteins have as yet been tested in the clinic, and the major focus has been on birch and grass pollen, two of the most common causes of IgE-mediated allergic disease. This article serves to justify the rational for using recombinant products and reviews the progress that has been made to date with their clinical assessment.

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References

  • Akdis CA, Blaser K (2001) Bypassing IgE and targeting T cells for specific immunotherapy of allergy. Trends Immunol 22:175–178

    Article  CAS  PubMed  Google Scholar 

  • Akdis CA, Blesken T, Akdis M et al (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102:98–106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Akdis M, Verhagen J, Taylor A et al (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 199:1567–1575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Allergome (2009) A platform for allergen knowledge, http://www.allergome.org

  • Andersson K, Lidholm J (2003) Characteristics and immunobiology of grass pollen allergens. Int Arch Allergy Immunol 130:87–107

    Article  CAS  PubMed  Google Scholar 

  • Breiteneder H, Hassfeld W, Pettenburger K et al (1988) Isolation and characterization of messenger RNA from male inflorescences and pollen of the white birch (Betula verrucosa). Int Arch Allergy Appl Immunol 87:19–24

    Article  CAS  PubMed  Google Scholar 

  • Breiteneder H, Pettenburger K, Bito A et al (1989) The gene coding for the major birch allergen, Bet vI, is highly homologous to a pea disease resistance response gene. EMBO J 8:1935–1938

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carballido JM, Carballido-Perrig N, Terres G et al (1992) Bee venom phospholipase A2-specific T cell clones from human allergic and non-allergic individuals: cytokine patterns change in response to the antigen concentration. Eur J Immunol 22:1357–1363

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Creticos PS, Schroeder JT, Hamilton RG et al (2006) Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. New Engl J Med 355:1445–1455

    Article  CAS  PubMed  Google Scholar 

  • Dahl R, Kapp A, Colombo G et al (2008) Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol 121:512–518

    Article  CAS  PubMed  Google Scholar 

  • Didier A, Malling HJ, Worm M et al (2007) Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 120:1338–1345

    Article  CAS  PubMed  Google Scholar 

  • Ferreira F, Briza P, Infuhr D et al (2006) Modified recombinant allergens for safer immunotherapy. Inflamm Allergy Drug Targets 5:5–14

    Article  CAS  PubMed  Google Scholar 

  • Frew AJ, Powell RJ, Corrigan CJ, Durham SR (2006) Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 117:319–325

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Grönlund H, Bergman T, Sandström K et al (2003) Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli. J Biol Chem 278:40144–40151

    Article  PubMed  Google Scholar 

  • Johansen N, Weber RW, Ipsen H et al (2009) Extensive IgE cross-reactivity towards the Pooideae grasses substantiated for a large number of grass-pollen-sensitized subjects. Int Arch Allergy Immunol 150:325–334

    Article  CAS  PubMed  Google Scholar 

  • Juniper EF, Guyatt GH (1991) Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis. Clin Exp Allergy 21:77–83

    Article  CAS  PubMed  Google Scholar 

  • Jutel M, Akdis M, Budak F et al (2003) IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205–1214

    Article  CAS  PubMed  Google Scholar 

  • Jutel M, Jaeger L, Suck R et al (2005) Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 116:608–613

    Article  CAS  PubMed  Google Scholar 

  • Kahlert H, Weber B, Cromwell O, Fiebig H (2003) Evaluation of the allergenicity of hypoallergenic recombinant derivatives of Bet v 1 using basophil activation vy CD203c expression measurement. In: Marone G (ed) Clinical immunology and allergy in medicine. JGC Editions, Naples, pp 735–740

    Google Scholar 

  • Kahlert H, Suck R, Weber B et al (2008) Characterization of a hypoallergenic recombinant Bet v 1 variant as a candidate for allergen-specific immunotherapy. Int Arch Allergy Immunol 145:193–206

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  • Kettner J, Meyer H, Narkus A et al (2007b) 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 (Abstract)

    Google Scholar 

  • Klimek L, Bachert C, Doemer C et al (2005) Specific immunotherapy with recombinant birch pollen allergen rBet v1-FV is clinically efficacious. Allergy Clin Immunol Int. Suppl 1:15 (Abstract)

    Google Scholar 

  • Larche M, Akdis CA, Valenta R (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6:761–771

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Martinez-Gomez JM, Johansen P, Rose H et al (2009) Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy. Allergy 64:172–178

    Article  CAS  PubMed  Google Scholar 

  • Moverare R, Elfman L, Vesterinen E et al (2002) Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP System. Allergy 57:423–430

    Article  CAS  PubMed  Google Scholar 

  • Narkus A, Kniest F, Menzel A et al. (2009) Clinical trials with recombinant allergens - three perspectives: industry. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe. Frankfurt AM 96:270–278

    Google Scholar 

  • Niederberger V, Valenta R (2006) Molecular approaches for new vaccines against allergy. Expert Rev Vaccines 5:103–110

    Article  CAS  PubMed  Google Scholar 

  • Niederberger V, Horak F, Vrtala S et al (2004) Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Nat Acad Sci USA 101:14677–14682

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Niederberger V, Reisinger J, Valent P et al (2007) Vaccination with genetically modified birch pollen allergens: Immune and clinical effects on oral allergy syndrome. J Allergy Clin Immunol 119:1013–1019

    Article  CAS  PubMed  Google Scholar 

  • Pauli G, Purohit A, Oster JP et al (2000) Comparison of genetically engineered hypoallergenic 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 30:1076–1084

    Article  CAS  PubMed  Google Scholar 

  • Pauli G, Larsen TH, Rak S et al (2008) Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol 122:951–960

    Article  CAS  PubMed  Google Scholar 

  • Purohit A, Niederberger V, Kronqvist M et al (2008) Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin Exp Allergy 38:1514–1525

    Article  CAS  PubMed  Google Scholar 

  • Rappuoli R, Douce G, Dougan G, Pizza M (1995) Genetic detoxification of bacterial toxins: a new approach to vaccine development. Int Arch Allergy Immunol 108:327–333 [Review] [39 refs]

    Article  CAS  PubMed  Google Scholar 

  • 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 116:347–354

    Article  CAS  PubMed  Google Scholar 

  • Ruedl C, Bachmann MF, Kopf M (2000) The antigen dose determines T helper cell subset development by regulation of CD40 ligand. Eur J Immunol 30:2056–2064

    Article  CAS  PubMed  Google Scholar 

  • Senti G, Kuster D, Martinez-Gomez JM et al (2009) Intralymphatic allergen specific immunotherapy using modified recombinant allergen targeting the MHC class II pathway: a double-blind placebo-controlled clinical trial in cat dander allergic patients. Allergy 64(Suppl 90):74 (Abstract)

    Google Scholar 

  • Sprung V, Pfaar O, Klimek L et al (2009) Safety and efficacy of recombinant grass pollen allergens: a dose – response study. Allergy 64(Suppl 90):147 [Abstract]

    Google Scholar 

  • 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 allergenicity. J Allergy Clin Immunol 106:124–134

    Article  CAS  PubMed  Google Scholar 

  • Tryba M (1994) Akuttherapie anaphylaktoider Reaktionen. Ergebnis einer interdisziplinären Konsensuskonferenz. Allergo J 3:211–224

    Google Scholar 

  • van der Heijden FL, van Neerven RJJ, van Katwijk M et al (1993) Serum-IgE-facilitated allergen presentation in atopic disease. J Immunol 150:3643–3650

    PubMed  Google Scholar 

  • van Hage-Hamsten M, Kronqvist M, Zetterström O et al (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 104:969–977

    Article  PubMed  Google Scholar 

  • Vrtala S, Hirtenlehner K, Vangelista L et al (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 99:1673–1681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vrtala S, Akdis CA, Budak F et al (2001a) T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies. J Immunol 165:6653–6659

    Google Scholar 

  • Vrtala S, Hirtenlehner K, Susani M et al (2001b) Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen, Bet v 1. FASEB J 15:2045–2047

    CAS  PubMed  Google Scholar 

  • 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 Meth 56:219–232

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Allergopharma Joachim Ganzer KG, Hermann-Koerner-Strasse 52, 21465, Reinbek, Germany

    Oliver Cromwell & Helmut Fiebig

  2. Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria

    Verena Niederberger

  3. ENT University Clinic, University of Vienna, Vienna, Austria

    Friedrich Horak

Authors
  1. Oliver Cromwell
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  2. Verena Niederberger
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  3. Friedrich Horak
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  4. Helmut Fiebig
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Corresponding author

Correspondence to Oliver Cromwell .

Editor information

Editors and Affiliations

  1. Christian Doppler Laboratory for Allergy, Medical University of Vienna, Vienna, Austria

    Rudolf Valenta

  2. Dynavax Technologies, Berkeley, California, USA

    Robert L. Coffman

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© 2011 Springer-Verlag Berlin Heidelberg

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Cromwell, O., Niederberger, V., Horak, F., Fiebig, H. (2011). Clinical Experience with Recombinant Molecules for Allergy Vaccination. In: Valenta, R., Coffman, R. (eds) Vaccines against Allergies. Current Topics in Microbiology and Immunology, vol 352. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_129

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