Skip to main content

Advertisement

SpringerLink
Log in

The Role of Synthetic Peptide Immuno-Regulatory Epitope (SPIRE) in the Treatment of Allergic Disease

  • Specific Immunotherapy (L Cox, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Opinion statement

Immunotherapy has been used for over a century for the treatment of allergic rhinitis, starting with the administration of whole allergens which are still in use today. Up-titration of allergen concentrations is thought to induce immune-tolerance, reducing symptoms upon exposure of the same allergen in the natural environment. More recently, peptide immunotherapy research aims to reduce sensitization to the allergen while utilizing a much shorter treatment schedule and avoiding the risk of anaphylactic reactions associated with whole allergen administration. Other immunotherapies undergoing clinical trials utilize linear joined peptides of the natural antigen, which are thought to avoid triggering anaphylaxis by selectively joining non-IgE binding allergen proteins. These novel therapies have been investigated using a variety of methods, including at controlled allergen challenge facilities (CACF) and in phase 3 trials in the “real world” setting. Experimental phase 2 trial designs were also used, the nasal allergen challenge (NAC) protocols, involving the direct exposure of the nasal mucosa to the allergen. The mechanism of action of peptide immunotherapies is thought to vary from that of conventional immunotherapies, though more research is needed to understand how desensitization occurs in each case. A shift from CD4+ to CD8+ Th cells is thought to be one way to explain this and is backed by change in cytokine expression in various experimental models.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

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

  1. Keith P, Desrosiers M, Laister T, Schellenberg R, Waserman S. The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients. Allergy, Asthma Clin Immunol. 2012;8(1):7. doi:10.1186/1710-1492-8-7.

    Article  Google Scholar 

  2. Reisacher WR, Suurna MV, Rochlin K, Bremberg MG, Tropper G. Oral mucosal immunotherapy for allergic rhinitis: a pilot study. Allergy Rhinol (Providence). 2016;7(1):21–8. doi:10.2500/ar.2016.7.0150.

    Article  Google Scholar 

  3. Reisacher W, Rudner S, Kotik V. Oral mucosal immunotherapy using a toothpaste delivery system for the treatment of allergic rhinitis. Int J Pharm Compd. 2014;18(4):287–90.

    Google Scholar 

  4. Senti G, Kündig TM. Intralymphatic immunotherapy. World Allergy Organ J. 2015;8(1):9. doi:10.1186/s40413-014-0047-7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. •• Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013;131(2):412–20. doi:10.1016/j.jaci.2012.10.056.Highlighting the rationale and effectiveness of intra-lymphatic injection of pollen allergen immunotherapy.

    Article  CAS  PubMed  Google Scholar 

  6. •• Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WCJ, Rutten-van Molken MPMH. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132(2):353–60.e2. doi:10.1016/j.jaci.2013.03.013.Study highlighting the difference in treatment adherence between clinical trials and real life where the average adherence to either SCIT or SLIT was at 18% over a 3 year treatment period.

    Article  PubMed  Google Scholar 

  7. •• Cox L, Compalati E, Kundig T, Larche M. New directions in immunotherapy. Curr Allergy Asthma Rep. 2013;13(2):178–95. doi:10.1007/s11882-012-0335-7.Review of the key difference between various routes for allergen immunotherapy administration.

    Article  CAS  PubMed  Google Scholar 

  8. • Maloney J, Berman G, Gagnon R, et al. Sequential treatment initiation with timothy grass and ragweed sublingual immunotherapy tablets followed by simultaneous treatment is well tolerated. J allergy Clin Immunol Pract. 2016;4(2):301–9.e2. doi:10.1016/j.jaip.2015.11.004.Investigating the effectiveness of administering SLIT tablets for 2 different allergens at the same time. Current recommendations advise against such protocols, mainly due to lack of adequate safety data. This study might provide an appropriate way for such administration.

    Article  PubMed  Google Scholar 

  9. •• Verhoef A, Alexander C, Kay AB, Larche M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2005;2(3):e78. doi:10.1371/journal.pmed.0020078.This study investigated the mechanism of immuno-tolerance induction by peptide immunotherapy. The main finding highlights the induction of CD4+ regulatory T cells.

    Article  PubMed  PubMed Central  Google Scholar 

  10. •• Niespodziana K, Focke-Tejkl M, Linhart B, et al. A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. J Allergy Clin Immunol. 2016;127(6):1562–1570.e6. doi:10.1016/j.jaci.2011.02.004.A study of the effectiveness of fusion protein immunotherapy derived from fusing hepatitis B virus derived proteins with non-allergenic portions of Fel d1 protein. The protein's effect in reducing IgE and Tcell medicated side effects were observed in animal models.

    Article  Google Scholar 

  11. Norman PS, Ohman Jr JL, Long AA, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med. 1996;154:1623–8.

    Article  CAS  PubMed  Google Scholar 

  12. Creticos PS. Advances in synthetic peptide immuno-regulatory epitopes. World Allergy Organ J. 2014;7(1) doi:10.1186/1939-4551-7-30.

  13. • Devillier P, Le Gall M, Horak F. The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy. Allergy. 2011;66(2):163–9. doi:10.1111/j.1398-9995.2010.02473.x.Describing the value of Controlled Allergen Challenge Facilities (CACFs) for testing and developing novel allergen immunotherapies.

    Article  CAS  PubMed  Google Scholar 

  14. • North M, Soliman M, Walker T, Steacy L, Ellis A. Controlled allergen challenge facilities and their unique contributions to allergic rhinitis research. Curr Allergy Asthma Rep. 2015;15(4):1–10. doi:10.1007/s11882-015-0514-4.Review of recent and historic use of Controlled Allergen Challenge Facilities (CACFs) internationally in evaluating various allergy therapies including allergen immunotherapies.

    Article  CAS  Google Scholar 

  15. •• Patel D, Couroux P, Hickey P, 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;131:103–7.Describing the use of a CACF in evaluating a novel Fel d1 peptide immunotherapy in a randomized controlled trial one year after the start of dosing.

    Article  CAS  PubMed  Google Scholar 

  16. •• Couroux P, Patel D, Armstrong K, Larche 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; doi:10.1111/cea.12488.Evaluating the effect of a novel Fel d1 peptide immunotherapy 2 years following treatment.

    PubMed  Google Scholar 

  17. Hafner R, Couroux P, Armstrong K, Patel D, Larche ML. Two year persistent treatment effect achieved after 4 doses of cat-peptide antigen desensitization (cat-PAD) in an environmental exposure chamber (EEC) model of cat allergy. J Allergy Clin Immunol. 2016;131(2):AB147. doi:10.1016/j.jaci.2012.12.1185.

    Google Scholar 

  18. Circassia announces top-line results from cat allergy phase III study. http://www.circassia.com/media/press-releases/circassia-announces-top-line-results-from-cat-allergy-phase-iii-study/.

  19. Neighbour H, Larché M, Steacy L, et al. The nasal allergen challenge protocol of the allergic rhinitis clinical investigator collaborative (AR-CIC): validation in a clinical trial of cat synthetic peptide immunoregulatory epitopes (Cat-SPIRE). J Allergy Clin Immunol. 2015;135(2):AB142. doi:10.1016/j.jaci.2014.12.1401.

    Article  Google Scholar 

  20. • Ellis AK, Soliman M, Steacy L, et al. The Allergic Rhinitis—Clinical Investigator Collaborative (AR-CIC): nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies. Allergy, Asthma Clin Immunol. 2015;11(1):16. doi:10.1186/s13223-015-0082-0.Highlighting key design features of phase 2 clinical trials utilizing Nasal Allergen Challenge method developed by the Allergic Rhinitis - Clinical Investigator Collaborative.

    Article  Google Scholar 

  21. Soliman M, North ML, Steacy LM, Thiele J, Adams DE, Ellis AK. Nasal allergen challenge studies of allergic rhinitis: a guide for the practicing clinician. Ann Allergy Asthma Immunol. 2014;113(3):250–6. doi:10.1016/j.anai.2014.06.018.

    Article  PubMed  Google Scholar 

  22. Narkus A, Lehnigk U, Haefner D, Klinger R, Pfaar O, Worm M. The placebo effect in allergen-specific immunotherapy trials. Clin Transl Allergy. 2013;3:42.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Larche M, Hickey P, Hebert J, Hafner R. Safety and tolerability of escalating doses of house dust mite-peptide antigen desensitization (HDM-PAD). J Allergy Clin Immunol. 2016;131(2):AB37. doi:10.1016/j.jaci.2012.12.814.

    Google Scholar 

  24. •• 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. 2016;129(2):AB368. doi:10.1016/j.jaci.2012.01.017.Describing a study of a novel peptide immunotherapy for Amb a1 (ragweed).

    Google Scholar 

  25. Hafner R, Couroux P, Armstrong K, Salapatek A, Patel D, Larche M. Persistent treatment effect achieved at one year after four doses of der p derived synthetic peptide immuno-regulatory epitopes in an exposure chamber model of house dust mite allergy. J Allergy Clin Immunol. 2016;133(2):AB289. doi:10.1016/j.jaci.2013.12.1023.

    Article  Google Scholar 

  26. Ellis A, Frankish C, O’Hehir R, et al. Treatment with grass synthetic peptides improves symptoms of grass-pollen-induced allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2017. In press

  27. • Ellis A, Frankish CW, Armstrong K, et al. Persistent treatment effect with grass synthetic peptide immuno-regulatory epitopes in grass allergy symptoms in an environmental exposure unit challenge after a second season of natural pollen exposure. J Allergy Clin Immunol. 2015;135(2):AB158. doi:10.1016/j.jaci.2014.12.1457.A CACF study highlighting the sustained clinical effectiveness of grass peptide immunotherapy following 2 years from the end of treatment and 2 seasons of natural exposure to grass pollen.

    Article  Google Scholar 

  28. Focke-Tejkl M, Weber M, Niespodziana K, et al. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy. J Allergy Clin Immunol. 2015;135(5):1207–1217.e11. doi:10.1016/j.jaci.2014.09.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Swoboda I, Balic N, Klug C, et al. A general strategy for the generation of hypoallergenic molecules for the immunotherapy of fish allergy. J Allergy Clin Immunol. 2013;132(4):979–81.e1. doi:10.1016/j.jaci.2013.04.027.

    Article  CAS  PubMed  Google Scholar 

  30. Marth K, Focke-Tejkl M, Lupinek C, Valenta R, Niederberger V. Allergen peptides, recombinant allergens and hypoallergens for allergen-specific immunotherapy. Curr Treat Options Allergy. 2014;1(1):91–106. doi:10.1007/s40521-013-0006-5.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Smith TRF, Alexander C, Kay AB, Larche M, Robinson DS. Cat allergen peptide immunotherapy reduces CD4(+) T cell responses to cat allergen but does not alter suppression by CD4(+) CD25(+) T cells: a double-blind placebo-controlled study. Allergy. 2004;59(10):1097–101. doi:10.1111/j.1398-9995.2004.00601.x.

    Article  CAS  PubMed  Google Scholar 

  32. Alexander C, Ying S, Kay AB, Larché M. Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-γ + T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin Exp Allergy. 2005;35(1):52–8. doi:10.1111/j.1365-2222.2005.02143.x.

    Article  CAS  PubMed  Google Scholar 

  33. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–55. doi:10.1016/j.jaci.2010.09.034.

    Article  PubMed  Google Scholar 

  34. Campbell JD, Buckland KF, McMillan SJ, et al. Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med. 2009;206(7):1535–47. doi:10.1084/jem.20082901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Walker MR, Kasprowicz DJ, Gersuk VH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+ CD25- T cells. J Clin Invest. 2003;112:1437–43.

    Article  CAS  PubMed  Google Scholar 

  36. •• Alexander C, Barkans J, Forsyth L, et al. Allergen-derived T-cell peptide immunotherapy in allergic asthmatic individuals is associated with induction of CD4+ IFN-gamma+/CD4+ CD25+ T cells and enhanced expression of TGF-beta and Notch-1 ligands at sites of cutaneous allergen challenge. J Allergy Clin Immunol. 2016;111(2):S197. doi:10.1016/S0091-6749(03)80677-2.This study highlights a possible mechanism of tolerance induction with treatment using peptide immunotherapy through increase CD4+ IFN-gamma+/CD4+CD25+ T cells.

    Article  Google Scholar 

  37. Moldaver DM, Bharhani MS, Wattie JN, et al. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35. Mucosal Immunol. 2014;7:379–390. doi:10.1038/mi.2013.56.

  38. •• Müller U, Akdis CA, Fricker M, et al. Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol. 1998;101(6):747–54. doi:10.1016/S0091-6749(98)70402-6.Study of bee venom peptide immunotherapy and a hypothesis of possible role for increased IgG4 as blocking anti-bodies.

    Article  PubMed  Google Scholar 

  39. Nouri-Aria KT, Wachholz PA, Francis JN, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol. 2004;172:3252–9.

    Article  CAS  PubMed  Google Scholar 

  40. Aalberse R. The role of IgG antibodies in allergy and immunotherapy. Allergy. 2011;66:28–30. doi:10.1111/j.1398-9995.2011.02628.x.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Research Unit, Kingston General Hospital, Kingston, ON, Canada

    Mena Soliman MBChB, MSc & Anne K Ellis MD, MSc, FRCPC

  2. Division of Allergy and Immunology, Department of Medicine, Queen’s University, Watkins 1D 76 Stuart Street, Kingston, ON, K7L 2V7, Canada

    Anne K Ellis MD, MSc, FRCPC

Authors
  1. Mena Soliman MBChB, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne K Ellis MD, MSc, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne K Ellis MD, MSc, FRCPC.

Ethics declarations

Conflict of Interest

Mena Soliman declares no conflicts of interest. Dr. Anne K Ellis declares grants to institution from Novartis, Pfizer, and GSK; Speaker’s Bureau from Novartis, Pfizer, Takeda, Meda, and Astra Zeneca; and is an Advisory Board Member for Novartis, Circassia Ltd and GSK.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Specific Immunotherapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soliman, M., Ellis, A.K. The Role of Synthetic Peptide Immuno-Regulatory Epitope (SPIRE) in the Treatment of Allergic Disease. Curr Treat Options Allergy 4, 22–29 (2017). https://doi.org/10.1007/s40521-017-0115-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-017-0115-7

Keywords

Search

Navigation