Abstract
Genetically engineered recombinant allergens have the ability to improve allergy diagnosis and are used as reference standards for analytical methods. In addition, the use of recombinant allergens in allergen-specific immunotherapy has long been considered potentially superior compared with the use of conventional extracts. The advantages are clear: A complex natural substance that is difficult to characterize is replaced by only those components relevant for treatment, which can be reproduced in very high quality. The challenges faced here include selecting the necessary allergen molecules and establishing a production method that meets all the regulatory requirements of marketing authorization. In addition to unmodified recombinant allergens, hypoallergenic variants with lower IgE reactivity can also be produced using genetic engineering techniques; proof of concept has been demonstrated for both these concepts in clinical trials.
The present chapter is based on, and modified from, an article by the authors published in 2015 in Allergo Journal International (Nandy A, Häfner D, Klysner S: Recombinant allergens for specific immunotherapy: Current concepts and developments. Allergo J Int 2015; 24:143–151).
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References
Cromwell O, Fiebig H, Suck R, et al. Strategies for recombinant allergen vaccines and fruitful results from first clinical trials. Immunol Allergy Clin North Am. 2006;26:261–81.
Cromwell O, Häfner D, Nandy A. Recombinant allergens for specific immunotherapy. J Allergy Clin Immunol. 2011;127:865–72.
Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016;137:339–49.
European Commission, editor. EudraLex: the rules governing medicinal products in the European Union, Volume 4: EU guidelines for good manufacturing practice for medicinal products for human and veterinary use, annex 2, manufacture of biological active substances and medicinal products for human use. 2010.
European Medicines Agency, Committee for Medicinal Products for Human Use.Guideline on Allergen Products: production and quality issues; note for guidance on specifications: test procedures and acceptance criteria for biotechnological/biological products CPMP/ICH/365/96 [Q6B]. 2008.
Fallrath JM, Kettner A, Dufour N, et al. Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: Results of a phase I trial. J Allergy Clin Immunol. 2003;111:854–56.
Hansen S, Mußler S, Meyer H, et al. First long-term efficacy data of subcutaneous specific immunotherapy with a recombinant birch pollen product. Allergy. 2011;66:62.
Jutel M, Jaeger L, Suck R, et al. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116:608–13.
Kahlert H, Suck R, Weber B, et al. Characterization of a hypoallergenic recombinant Bet v 1 variant as a candidate for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2008;145:193–206.
Kettner J, Meyer H, Narkus A, et al. Specific immunotherapy with recombinant birch pollen allergen rBet v 1-FV is clinically efficacious—results of a phase III study [abstract]. Allergy. 2007a;62:33.
Kettner J, Meyer H, Cromwell O, et al. Specific immunotherapy with recombinant birch pollen allergen Bet v 1-FV. Results of 2 years treatment (Phase II Trial) [Abstract]. Allergy. 2007b;62:262.
Klimek L, Schendzielorz P, Pinol R, et al. Specific subcutaneous immunotherapy with recombinant grass pollen allergens: first randomized dose-ranging safety study. Clin Exp Allergy. 2012;42:936–45.
Klimek L, Bachert C, Lukat KF, et al. Allergy immunotherapy with a hypoallergenic recombinant birch pollen allergen rBet v 1-FV in a randomized controlled trial. Clin Transl Allergy. 2015;5:28.
Marth K, Focke-Tejkl M, Lupinek C, et al. Allergen peptides, recombinant allergens and hypoallergens for allergen-specific immunotherapy. Curr Treat Options Allergy. 2014;1:91–106.
Meyer W, Narkus A, Salapatek A, et al. Efficacy and safety of four dose regimes of a hypoallergenic recombinant birch pollen major allergen (rBet v 1-FV) in birch pollen allergic patients studied in an environmental exposure chamber [Abstract]. Allergy. 2012;67:89.
Narkus A, Kniest F, Menzel A et al. Clinical trials with recombinant allergens—three perspectives: industry. Arbeiten aus dem Paul-Ehrlich-Institut, 12th International Paul-Ehrlich-Seminar, Bad Homburg. Chmielorz, Wiesbaden; 2008. p. 270–8.
Niederberger V, Horak F, Vrtala S, et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Nat Acad Sci USA. 2004;101 Suppl 2:14677–82.
Niederberger V, Marth K, Eckl-Dorna J, et al. Skin test evaluation of a novel peptide carrier-based vaccine, BM32, in grass pollen-allergic patients. J Allergy Clin Immunol. 2015;136:1101–3.
Pauli G, Larsen TH, Rak S, et al. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2008;122:951–60.
Pellaton C, Perrin Y, Boudousquie C, et al. Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides. Clin Transl Allergy. 2013;3:17.
Purohit A, Niederberger V, Kronquist M, et al. Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin Exp Allergy. 2008;38:1514–25.
Radauer C, Nandy A, Ferreira F, et al. Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences. Allergy. 2014;69:413–9.
Rak S, De Blay F, Worm M, et al. Efficacy and safety of recombinant Bet v 1 (rBet v 1) tablets in sublingual immunotherapy [abstract]. Allergy. 2010;65 Suppl 65:4.
Senti G, Kuster D, Martinez-Gomez J, et al. 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 [abstract]. Allergy. 2009;64 Suppl 90:74.
Senti G, Crameri R, Kuster D, et al. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012;129:1290–6.
Suck R, Kamionka T, Schaffer B, et al. Bacterially expressed and optimized recombinant Phl p 1 is immunobiochemically equivalent to natural Phl p 1. Biochim Biophy Acta. 2006;1764:1701–9.
Spertini F, Perrin Y, Audran R, et al. Safety and immunogenicity of immunotherapy with Bet v 1-derived contiguous overlapping peptides. J Allergy Clin Immunol. 2014;134:239–40.
Swoboda I, Bugajska-Schretter A, Linhart B, et al. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol. 2007;178:6290–6.
Valenta R, Lidholm J, Niederberger V, et al. The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy. 1999;29:896–904.
Winther L, Poulsen LK, Robin B, et al. Safety and tolerability of recombinant Bet v 1 (rBet v 1) tablets in sublingual immunotherapy SLIT [abstract]. J Allergy Clin Immunol. 2009;123(Suppl):S215.
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Nandy, A., Creticos, P.S., Häfner, D. (2017). Recombinant Allergens in Specific Immunotherapy. In: Kleine-Tebbe, J., Jakob, T. (eds) Molecular Allergy Diagnostics. Springer, Cham. https://doi.org/10.1007/978-3-319-42499-6_26
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DOI: https://doi.org/10.1007/978-3-319-42499-6_26
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