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Utility and Comparative Efficacy of Recombinant Allergens Versus Allergen Extract

  • Asthma (WJ Calhoun and V Ortega, Section Editors)
  • Published:
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Abstract

Allergy immunotherapy (AIT) is the only disease-modifying therapy for the treatment of allergic diseases. Although its efficacy and utility are well-established, the potential for serious adverse events, cumbersome and lengthy treatment protocols, and variability of natural allergen preparations have limited its widespread application. Recent advances in recombinant technology have opened new avenues for the development of AIT vaccines. The purpose of this review is to highlight recent evidence on the use of novel recombinant vaccines and review the mechanisms, efficacy, safety, and limitations of AIT. Emerging evidence suggests that recombinant vaccines may provide a viable treatment alternative that improves on the limitations of natural extract therapy while maintaining efficacy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Platts-Mills TAE. The allergy epidemics: 1870−2010. J Allergy Clin Immunol. 2015;136(1):3–13. doi:10.1016/j.jaci.2015.03.048.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Freeman J. Further observations on the treatment of hay fever by hypodermic inoculations of pollen vaccine. Lancet. 1911;178(4594):814–7. doi:10.1016/S0140-6736(01)40417-X.

    Article  Google Scholar 

  3. Noon L. Prophylactic inoculation against hayfever. Lancet. 1911;1(4580):1572–3. doi:10.1016/S0140-6736(00)78276-6.

    Article  Google Scholar 

  4. Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6(10):761–71. doi:10.1038/nri1934.

    Article  PubMed  Google Scholar 

  5. Canonica GW, Passalacqua G. Noninjection routes for immunotherapy. J Allergy Clin Immunol. 2003;111(3):437–48. doi:10.1067/mai.2003.129.

    Article  PubMed  Google Scholar 

  6. Calderón MA, Casale TB, Togias A, Bousquet J, Durham SR, Demoly P. Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to registration and beyond. J Allergy Clin Immunol. 2011;127(1):30–8. doi:10.1016/j.jaci.2010.08.024.

    Article  PubMed  Google Scholar 

  7. Alvarez-Cuesta E, Cuesta-Herranz J, Puyana-Ruiz J, Cuesta-Herranz C, Blanco-Quirós A. Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study. J Allergy Clin Immunol. 1994;93(3):556–66. doi:10.1016/S0091-6749(94)70067-2.

    Article  CAS  PubMed  Google Scholar 

  8. Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. Sub-lingual immunotherapy. World Allergy Organization J. 2009;2(11):233–6. doi:10.1097/WOX.0b013e3181c6c379.

    Article  Google Scholar 

  9. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 SUPPL):S1–S55. doi:10.1016/j.jaci.2010.09.034.

    Article  PubMed  Google Scholar 

  10. • Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergen immunotherapy II: mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016;137(2):358–68. doi:10.1016/j.jaci.2015.12.1300. Comprehensive International consenus statement on allergen immunotherapy focusing on key mechanisms of AIT-triggered tolerance, requirements in allergen standardizaiton, and regulatory guidance

    Article  PubMed  Google Scholar 

  11. • Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136(3):556–68. doi:10.1016/j.jaci.2015.04.047. Comprehensive International consensus statement on best AIT practices

    Article  PubMed  Google Scholar 

  12. Linhart B, Hartl A, Jahn-Schmid B, Verdino P, Keller W, Krauth MT, et al. A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination. J Allergy Clin Immunol. 2005;115(5):1010–6. doi:10.1016/j.jaci.2004.12.1142.

    Article  CAS  PubMed  Google Scholar 

  13. Linhart B, Jahn-Schmid B, Verdino P, Keller W, Ebner C, Kraft D, et al. Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity. FASEB J. 2002;16(10):1301–3. doi:10.1096/fj.01-1012fje.

    CAS  PubMed  Google Scholar 

  14. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116(3):608–13. doi:10.1016/j.jaci.2005.06.004.

    Article  CAS  PubMed  Google Scholar 

  15. • Pauli G, Larsen TH, Rak S, Horak F, Pastorello E, Valenta R, et al. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2008;122(5):951–60. doi:10.1016/j.jaci.2008.09.017. Multicenter, randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of recombinant birch pollen vaccine, natural birch pollen, and placebo in 134 patients.

    Article  CAS  PubMed  Google Scholar 

  16. Purohit A, Niederberger V, Kronqvist M, Horak F, Grönneberg R, Suck R, et al. Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin Exp Allergy. 2008;38(9):1514–25. doi:10.1111/j.1365-2222.2008.03042.x.

    Article  CAS  PubMed  Google Scholar 

  17. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci U S A. 2004;101(Suppl):14677–82. doi:10.1073/pnas.0404735101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Reisinger J, Horak F, Pauli G, Van Hage M, Cromwell O, König F, et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005;116(2):347–54. doi:10.1016/j.jaci.2005.04.003.

    Article  CAS  PubMed  Google Scholar 

  19. Kahlert H, Suck R, Weber B, Nandy A, Wald M, Keller W, et al. Characterization of a hypoallergenic recombinant Bet v 1 variant as a candidate for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2008;145(3):193–206. doi:10.1159/000109288.

    Article  CAS  PubMed  Google Scholar 

  20. Chen KW, Blatt K, Thomas WR, Swoboda I, Valent P, Valenta R, et al. Hypoallergenic der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy. J Allergy Clin Immunol. 2012;130(2):435–43. doi:10.1016/j.jaci.2012.05.035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Meyer W, Narkus A, Salapatek AM, Häfner D. Double-blind, placebo-controlled, dose-ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber. Allergy. 2013;68(6):724–31. doi:10.1111/all.12148.

    Article  CAS  PubMed  Google Scholar 

  22. Linhart B, Focke-Tejkl M, Weber M, Narayanan M, Neubauer A, Mayrhofer H, et al. Molecular evolution of hypoallergenic hybrid proteins for vaccination against grass pollen allergy. J Immunol (Baltimore, MD: 1950). 2015;194(8):4008–18. doi:10.4049/jimmunol.1400402.

    Article  CAS  Google Scholar 

  23. Norman PS, Ohman JL Jr, Long AA, Creticos PS, Gefter MA, Shaked Z, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med. 1996;154(6):1623–8. doi:10.1164/ajrccm.154.6.8970345.

    Article  CAS  PubMed  Google Scholar 

  24. Simons FE, Imada M, Li Y, Watson WT, HayGlass KT. Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol. 1996;8(12):1937–45.

    Article  CAS  PubMed  Google Scholar 

  25. Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu DT. The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin Immunol (Orlando, Fla). 1999;93(3):222–31. doi:10.1006/clim.1999.4795.

    Article  CAS  Google Scholar 

  26. Oldfield WLG, Larché M, Kay AB. Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet. 2002;360(9326):47–53. doi:10.1016/S0140-6736(02)09332-7.

    Article  CAS  PubMed  Google Scholar 

  27. Worm M, Lee HH, Kleine-Tebbe J, Hafner RP, Laidler P, Healey D, et al. Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. J Allergy Clin Immunol. 2011;127(1) doi:10.1016/j.jaci.2010.11.029.

  28. Patel D, Couroux P, Hickey P, Salapatek AM, Laidler P, Larché M, et al. Fel d 1-derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: a randomized, placebo-controlled study. J Allergy Clin Immunol. 2013;131(1):103-9.e1-7. doi:10.1016/j.jaci.2012.07.028.

    Article  PubMed  Google Scholar 

  29. Couroux P, Patel D, Armstrong K, Larché M, Hafner RP. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects. Clin Exp Allergy. 2015;45(5):974–81. doi:10.1111/cea.12488.

    Article  CAS  PubMed  Google Scholar 

  30. • Ellis AK, Frankish CW, O'Hehir RE, Armstrong K, Steacy L, Larché M, et al. Treatment with grass allergen peptides improves symptoms of grass pollen–induced allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2017:1–11. doi:10.1016/j.jaci.2016.11.043. Multicenter, randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of Grass-SPIRE vs. placebo in 282 patients.

  31. Pellaton C, Perrin Y, Boudousquié C, Barbier N, Wassenberg J, Corradin G, et al. Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides. Clin Trans Allergy. 2013;3(1):17. doi:10.1186/2045-7022-3-17.

    Article  CAS  Google Scholar 

  32. • Spertini F, DellaCorte G, Kettner A, de Blay F, Jacobsen L, Jutel M, et al. Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1–derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: results of a phase IIb study. J Allergy Clin Immunol. 2016;138(1):162–8. doi:10.1016/j.jaci.2016.02.044. Multicenter, randomized, double-blind, placebo-controlled phase IIb trial comparing the safety and efficacy of birch-COP immunotherapy versus placebo in 239 patients.

    Article  CAS  PubMed  Google Scholar 

  33. Campana R, Vrtala S, Maderegger B, Jertschin P, Stegfellner G, Swoboda I, et al. Hypoallergenic derivatives of the major birch pollen allergen Bet v 1 obtained by rational sequence reassembly. J Allergy Clin Immunol. 2010;126(5):1024–31.e8. doi:10.1016/j.jaci.2010.05.023.

    Article  CAS  PubMed  Google Scholar 

  34. Niespodziana K, Focke-Tejkl M, Linhart B, Civaj V, Blatt K, Valent P, et al. A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. J Allergy Clin Immunol. 2011;127(6):1562–70. doi:10.1016/j.jaci.2011.02.004.

    Article  CAS  PubMed  Google Scholar 

  35. Marth K, Breyer I, Focke-Tejkl M, Blatt K, Shamji MH, Layhadi J, et al. A nonallergenic birch pollen allergy vaccine consisting of hepatitis PreS-fused Bet v 1 peptides focuses blocking IgG toward IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype. J Immunol (Baltimore, MD: 1950). 2013;190(7):3068–78. doi:10.4049/jimmunol.1202441.

    Article  CAS  Google Scholar 

  36. Banerjee S, Weber M, Blatt K, Swoboda I, Focke-Tejkl M, Valent P, et al. Conversion of Der p 23, a new major house dust mite allergen, into a hypoallergenic vaccine. J Immunol (Baltimore, MD: 1950). 2014;192(10):4867–75. doi:10.4049/jimmunol.1400064.

    Article  CAS  Google Scholar 

  37. Focke-Tejkl M, Weber M, Niespodziana K, Neubauer A, Huber H, Henning R, et al. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy. J Allergy Clin Immunol. 2015;135(5):1207–11e11. doi:10.1016/j.jaci.2014.09.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. • Zieglmayer P, Focke-Tejkl M, Schmutz R, Lemell P, Zieglmayer R, Weber M, et al. Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy. EBioMedicine. 2016;11:43–57. doi:10.1016/j.ebiom.2016.08.022. Randomized, double-blind, placebo-controlled trial to determine the safety, clinical efficacy, and immunologic mechanisms of B-cell epitope based vaccine for grass pollen allergy in 70 patients.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Fujita H, Soyka MB, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. Clin Trans Allergy. 2012;2:2. doi:10.1186/2045-7022-2-2.

    Article  CAS  Google Scholar 

  40. Han D, Wang C, Lou W, Gu Y, Wang Y, Zhang L. Allergen-specific IL-10-secreting type I T regulatory cells, but not CD4(+)CD25(+)Foxp3(+) T cells, are decreased in peripheral blood of patients with persistent allergic rhinitis. Clin Immunol. 2010;136(2):292–301. doi:10.1016/j.clim.2010.03.006.

    Article  CAS  PubMed  Google Scholar 

  41. • Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133(3):621–31. doi:10.1016/j.jaci.2013.12.1088. Comprehensive review on the role of suppressor cells in immune tolerance to allergens.

    Article  CAS  PubMed  Google Scholar 

  42. Aktories K, Fakultät M, Pharmakologie K, Albert AI, Freiburg L-U, Compans RW, et al. Vaccines against allergies. Current topics in microbiology and immunology. Berlin: Springer Berlin Heidelberg; 2011.

    Google Scholar 

  43. Jutel M, Akdis CA. Immunological mechanisms of allergen-specific immunotherapy. Allergy. 2011;66(6):725–32. doi:10.1111/j.1398-9995.2011.02589.x.

    Article  CAS  PubMed  Google Scholar 

  44. Lou W, Wang C, Wang Y, Han D, Zhang L. Responses of CD4+ CD25+ Foxp3+ and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children. Pediatr Allergy Immunol. 2012;23(2):141–50. doi:10.1111/j.1399-3038.2011.01249.x.

    Article  Google Scholar 

  45. Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol. 2012;30:221–41. doi:10.1146/annurev-immunol-020711-074934.

    Article  CAS  PubMed  Google Scholar 

  46. Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M. Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy. 2008;63(11):1455–63. doi:10.1111/j.1398-9995.2008.01774.x.

    Article  CAS  PubMed  Google Scholar 

  47. Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131(5):1288–96.e3. doi:10.1016/j.jaci.2013.01.049.

    Article  PubMed  Google Scholar 

  48. Jutel M, Kosowska A, Smolinska S. Allergen immunotherapy: past, present, and future. Allergy, Asthma Immunol Res. 2016;8(3):191–7. doi:10.4168/aair.2016.8.3.191.

    Article  Google Scholar 

  49. Bae JM, Choi YY, Park CO, Chung KY, Lee KH. Efficacy of allergen-specific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. 2013;132(1):110–7. doi:10.1016/j.jaci.2013.02.044.

    Article  PubMed  Google Scholar 

  50. Calderon MMA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S, et al. Allergen injection immunotherapy for seasonal allergic rhinitis ( review ) allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Rev J. 2009;5(1):1279–379. doi:10.1002/14651858.CD001936.pub2.Copyright.

    Google Scholar 

  51. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database of Systematic Reviews. 2010; (8). doi:10.1002/14651858.CD001186.pub2.

  52. Frew AJ, Powell RJ, Corrigan CJ, Durham SR. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006;117(2):319–25. doi:10.1016/j.jaci.2005.11.014.

    Article  CAS  PubMed  Google Scholar 

  53. Möller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002;109(2):251–6. doi:10.1067/mai.2002.121317.

    Article  PubMed  Google Scholar 

  54. Inal A, Altintas DU, Yilmaz M, Karakoc GB, Kendirli SG, Sertdemir Y. Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite. J Investig Allergol Clin Immunol. 2007;17(2):85–91.

    CAS  PubMed  Google Scholar 

  55. Des Roches A, Paradis L, Menardo JL, Bouges S, Daures JP, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol. 1997;99(4):450–3.

    Article  CAS  PubMed  Google Scholar 

  56. Linhart B, Valenta R. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives. Vaccine. 2012;30(29):4328–35. doi:10.1016/j.vaccine.2011.11.011.

    Article  CAS  PubMed  Google Scholar 

  57. Grier TJ. How's my dosing? A one-step, math-free guide for comparing your clinic’s maintenance immunotherapy doses to current practice parameter recommendations. Ann Allergy Asthma Immunol. 2012;108(3):201–5. doi:10.1016/j.anai.2012.01.011.

    Article  PubMed  Google Scholar 

  58. Passalacqua G, Canonica GW. Allergen immunotherapy: history and future developments. Immunol Allergy Clin N Am. 2016;36(1):1–12.

    Article  Google Scholar 

  59. Lockey RF, Nicoara-Kasti GL, Theodoropoulos DS, Bukantz SC. Systemic reactions and fatalities associated with allergen immunotherapy. Ann Allergy Asthma Immunol. 2001;87(1 Suppl 1):47–55. doi:10.1016/S1081-1206(10)62195-3.

    Article  CAS  PubMed  Google Scholar 

  60. Nettis E, Giordano D, Ferrannini A, Tursi A. Systemic reactions to allergen immunotherapy: a review of the literature. Immunopharmacol Immunotoxicol. 2003;25(1):1–11. doi:10.1081/IPH-120018279.

    Article  PubMed  Google Scholar 

  61. Miehlke S, Alpan O, Schröder S, Straumann A. Induction of eosinophilic esophagitis by sublingual pollen immunotherapy. Case Reps Gastroenterol. 2013;7(3):363–8. doi:10.1159/000355161.

    Article  Google Scholar 

  62. • Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. AAAAI/ACAAI surveillance study of subcutaneous immunotherapy, years 2008–2012: an update on fatal and nonfatal systemic allergic reactions. J Allergy Clin Immunol. 2014;2(2):161–7.e3. doi:10.1016/j.jaip.2014.01.004. Summary of annual survey results from 2008-2012 of AAAAI and ACAAI members on SCIT-related fatal and nonfatal systemic reactions of varying severity.

    Article  Google Scholar 

  63. Cox LS, Linnemann DL, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol. 2006;117(5):1021–35. doi:10.1016/j.jaci.2006.02.040.

    Article  PubMed  Google Scholar 

  64. Larché M. Peptide therapy for allergic diseases: basic mechanisms and new clinical approaches. Pharmacol Ther. 2005;108(3):353–61. doi:10.1016/j.pharmthera.2005.05.004.

    Article  PubMed  Google Scholar 

  65. Henmar H, Lund G, Lund L, Petersen A, Wurtzen PA. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin Exp Immunol. 2008;153(3):316–23. doi:10.1111/j.1365-2249.2008.03710.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Casale TB, Stokes JR. Future forms of immunotherapy. J Allergy Clin Immunol. 2011;127(1):8–15. doi:10.1016/j.jaci.2010.10.034.

    Article  PubMed  Google Scholar 

  67. Valenta R, Niederberger V. Recombinant allergens for immunotherapy. J Allergy Clin Immunol. 2007;119(4):826–30. doi:10.1016/j.jaci.2007.01.025.

    Article  CAS  PubMed  Google Scholar 

  68. • O’Hehir RE, Prickett SR, Rolland JM. T cell epitope peptide therapy for allergic diseases. Curr Allergy Asthma Rep. 2016;16(2):1–9. doi:10.1007/s11882-015-0587-0. Comprehensive review on the mechanisms and studies on T-cell epitope peptide therapy for allergic diseases.

    Google Scholar 

  69. Valenta R, Niespodziana K, Focke-Tejkl M, Marth K, Huber H, Neubauer A, et al. Recombinant allergens: what does the future hold? J Allergy Clin Immunol. 2011;127(4):860–4. doi:10.1016/j.jaci.2011.02.016.

    Article  CAS  PubMed  Google Scholar 

  70. Klimek L, Schendzielorz P, Pinol R, Pfaar O. Specific subcutaneous immunotherapy with recombinant grass pollen allergens: first randomized dose-ranging safety study. Clin Exp Allergy. 2012;42(6):936–45. doi:10.1111/j.1365-2222.2012.03971.x.

    Article  CAS  PubMed  Google Scholar 

  71. Chapman MD, Smith AM, Vailes LD, Arruda LK, Dhanaraj V, Pomés A, et al. Recombinant allergens for diagnosis and therapy of allergic disease. J Allergy Clin Immunol. 2000;106:409–18.

    Article  CAS  PubMed  Google Scholar 

  72. Valenta R, Campana R, Marth K, van Hage M. Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic approaches. J Intern Med. 2012;272(2):144–57. doi:10.1111/j.1365-2796.2012.02556.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gafvelin G, Thunberg S, Kronqvist M, Gronlund H, Gronneberg R, Troye-Blomberg M, et al. 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. 2005;138(1):59–66. doi:10.1159/000087358.

    Article  CAS  PubMed  Google Scholar 

  74. Nony E, Bouley J, Le Mignon M, Lemoine P, Jain K, Horiot S, et al. Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen-allergic patients. Allergy. 2015;70(7):795–804. doi:10.1111/all.12622.

    Article  CAS  PubMed  Google Scholar 

  75. Mothes-Luksch N, Stumvoll S, Linhart B, Focke M, Krauth M-T, Hauswirth A, et al. Disruption of allergenic activity of the major grass pollen allergen Phl p 2 by reassembly as a mosaic protein. J Immunol (Baltimore, MD: 1950). 2008;181(7):4864–73. doi:10.4049/jimmunol.181.7.4864.

    Article  CAS  Google Scholar 

  76. Campana R, Vrtala S, Maderegger B, Dall'Antonia Y, Zafred D, Blatt K, et al. Altered IgE epitope presentation: a model for hypoallergenic activity revealed for Bet v 1 trimer. Mol Immunol. 2011;48(4):431–41. doi:10.1016/j.molimm.2010.09.016.

    Article  CAS  PubMed  Google Scholar 

  77. Larché M. Mechanisms of peptide immunotherapy in allergic airways disease. Ann Am Thoracic Soc. 2014;11:S292–S6. doi:10.1513/AnnalsATS.201402-090AW.

    Article  Google Scholar 

  78. Hoffmann HJ, Valovirta E, Pfaar O, Moingeon P, Schmid JM, Skaarup SH, et al. Novel approaches and perspectives in allergen immunotherapy. Allergy. 2017;38(1):42–9. doi:10.1111/all.13135.

    Google Scholar 

  79. Incorvaia C, Montagni M, Ridolo E. The efficiency of peptide immunotherapy for respiratory allergy. Expert Rev Clin Pharmacol. 2016;2433:1–7. doi:10.1586/17512433.2016.1157017.

    Google Scholar 

  80. Haselden BM, Kay AB, Larché M. Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med. 1999;189(12):1885–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hafner RP, Salapatek A, Patel D, Larché M, Laidler P. Validation of peptide immunotherapy as a new approach in the treatment of allergic rhinoconjunctivitis: the clinical benefits of treatment with Amb a 1 derived T cell epitopes. J Allergy Clin Immunol. 2012;129(2):AB368–AB. doi:10.1016/j.jaci.2012.01.017.

    Article  Google Scholar 

  82. Shamji M, Kasche E, Zadoyan G, editors. Hydrolyzed Lolium perenne peptide fragments administered subcutaneously to hay fever patients induce allergen-specific IgG4 and blocking antibodies after two or more weeks of treatment. EAACI Annual Meeting, Barcelona, 2015.

  83. Pene J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF, et al. Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol. 1998;102(4 I):571–8. doi:10.1016/S0091-6749(98)70294-5.

    Article  CAS  PubMed  Google Scholar 

  84. Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, et al. Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy. 2006;36(4):465–74. doi:10.1111/j.1365-2222.2006.02469.x.

    Article  CAS  PubMed  Google Scholar 

  85. Verhoef A, Alexander C, Kay AB, Larché M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2005;2(3):0253–61. doi:10.1371/journal.pmed.0020078.

    Article  CAS  Google Scholar 

  86. Fellrath JM, Kettner A, Dufour N, Frigerio C, Schneeberger D, Leimgruber A, 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(4):854–61. doi:10.1067/mai.2003.1337.

    Article  CAS  PubMed  Google Scholar 

  87. Kämmerer R, Chvatchko Y, Kettner A, Dufour N, Corradin G, Spertini F. Modulation of T-cell response to phospholipase A2 and phospholipase A2-derived peptides by conventional bee venom immunotherapy. J Allergy Clin Immunol. 1997;100(1):96–103. doi:10.1016/S0091-6749(97)70200-8.

    Article  PubMed  Google Scholar 

  88. Spertini F, Jutel M, Jacobsen L, de Blay F, Worm M, Della Corte G, et al. Sustained efficacy of allert allergy vaccine after a second birch pollen season: a phase IIb. J Allergy Clin Immunol. 2015;135(2):AB143–AB. doi:10.1016/j.jaci.2014.12.1402.

    Article  Google Scholar 

  89. Spertini F, Perrin Y, Audran R, Pellaton C, Boudousquié C, Barbier N, et al. Safety and immunogenicity of immunotherapy with Bet v 1-derived contiguous overlapping peptides. J Allergy Clin Immunol. 2014;134(1):239–40 doi:10.1016/j.jaci.2014.04.001.

    Article  CAS  PubMed  Google Scholar 

  90. Focke M, Mahler V, Ball T, Sperr WR, Majlesi Y, Valent P, et al. Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination. FASEB J. 2001;15(11):2042–4. doi:10.1096/fj.01-0016fje.

    CAS  PubMed  Google Scholar 

  91. Focke M, Swoboda I, Marth K, Valenta R. Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin e and T cell reactivity. Clin Exp Allergy. 2010;40(3):385–97. doi:10.1111/j.1365-2222.2009.03443.x.

    Article  CAS  PubMed  Google Scholar 

  92. Focke M, Linhart B, Hartl A, Wiedermann U, Sperr WR, Valent P et al. Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination. Clinical and Experimental Allergy. 2004;34(10):1525-33. doi:10.1111/j.1365-2222.2004.02081.x.

  93. Valenta R, Campana R, Focke-Tejkl M, Niederberger V. Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: lessons from the past and novel mechanisms of action for the future. J Allergy Clin Immunol. 2016;137(2):351–7. doi:10.1016/j.jaci.2015.12.1299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. William Calhoun for his critical review of this manuscript.

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  1. Patel and Chambliss contributed equally to this work

Authors and Affiliations

  1. Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Hardik D. Patel

  2. Department of Pediatrics, Division of Clinical and Experimental Immunology and Infectious Disease, University of Texas Medical Branch, 301 University Blvd, Route 0372, Galveston, TX, 77555, USA

    Jeffrey M. Chambliss & Meera R. Gupta

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  1. Hardik D. Patel
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  2. Jeffrey M. Chambliss
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  3. Meera R. Gupta
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Correspondence to Meera R. Gupta.

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This article is part of the Topical Collection on Asthma

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Patel, H.D., Chambliss, J.M. & Gupta, M.R. Utility and Comparative Efficacy of Recombinant Allergens Versus Allergen Extract. Curr Allergy Asthma Rep 17, 63 (2017). https://doi.org/10.1007/s11882-017-0727-9

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