Advertisement

Could This Be IT? Epicutaneous, Sublingual, and Subcutaneous Immunotherapy for the Treatment of Food Allergies

  • Mary Grace Baker
  • Julie WangEmail author
Food Allergy (E Kim, Section Editor)
  • 42 Downloads
Part of the following topical collections:
  1. Topical Collection on Food Allergy

Abstract

Purpose of Review

Over the last decade, there has been a spark in innovation in the development of therapies for food allergy. Herein, we describe the background and recent advances for food-specific immunotherapies including epicutaneous (EPIT), sublingual (SLIT), and subcutaneous (SCIT).

Recent Findings

Studies have progressed most quickly for the treatment of peanut allergy. Data from the phase 3 EPIT trial add to the accumulating evidence that this will be a viable therapy for peanut allergy. Studies for SLIT and SCIT remain in earlier phases with promising results.

Summary

This is an exciting era for the treatment of food allergy. Multiple therapies are under investigation, each with their own potential advantages. Specific strengths and limitations of each of these therapies may provide an opportunity to personalize the choice of therapy for individual patients.

Keywords

Food allergy Food hypersensitivity Anaphylaxis Peanut hypersensitivity Nut and Peanut hypersensitivity 

Abbreviations

APC

Antigen-presenting cell

DBPCFC

Double-blind, placebo-controlled food challenge

ED

Eliciting dose

EPIT

Epicutaneous immunotherapy

EVP

Epicutaneous Viaskin® Patch

IgE

Immunoglobulin E

IgG4

Immunoglobulin G4

IT

Immunotherapy

OIT

Oral immunotherapy

SCIT

Subcutaneous immunotherapy

SLIT

Sublingual immunotherapy

TH1

T helper cell type 1

TH2

T helper cell type 2

Treg

T regulatory cell

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Wang received research support from NIAID, Aimmune, DBV Therapeutics, Regeneron; consultancy fees from ALK Abello and DBV Technologies; and royalties from UpToDate.

Dr. Baker was supported in part by the Louis and Rachel Rudin Foundation.

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.

References

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

  1. 1.
    Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention and management. J Allergy Clin Immunol. 2018;141(1):41–58.  https://doi.org/10.1016/j.jaci.2017.11.003.CrossRefPubMedGoogle Scholar
  2. 2.
    National Academies of Sciences E, Medicine, Health, Medicine D, Food, Nutrition B, et al. In: Oria MP, Stallings VA, editors. Finding a path to safety in food allergy: assessment of the Global Burden, Causes, Prevention, Management, and Public Policy. Washington (DC): National Academies Press (US); 2016.Google Scholar
  3. 3.
    Osborne NJ, Koplin JJ, Martin PE, Gurrin LC, Lowe AJ, Matheson MC, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 2011;127(3):668–76.e1–2.  https://doi.org/10.1016/j.jaci.2011.01.039.CrossRefPubMedGoogle Scholar
  4. 4.
    King RM, Knibb RC, Hourihane JOB. Impact of peanut allergy on quality of life, stress and anxiety in the family. Allergy. 2009;64(3):461–8.  https://doi.org/10.1111/j.1398-9995.2008.01843.x.CrossRefPubMedGoogle Scholar
  5. 5.
    Flokstra-de Blok BM, Dubois AE, Vlieg-Boerstra BJ, Oude Elberink JN, Raat H, DunnGalvin A, et al. Health-related quality of life of food allergic patients: comparison with the general population and other diseases. Allergy. 2010;65(2):238–44.  https://doi.org/10.1111/j.1398-9995.2009.02121.x.CrossRefPubMedGoogle Scholar
  6. 6.
    Simonte SJ, Ma S, Mofidi S, Sicherer SH. Relevance of casual contact with peanut butter in children with peanut allergy. J Allergy Clin Immunol. 2003;112(1):180–2.  https://doi.org/10.1067/mai.2003.1486.CrossRefPubMedGoogle Scholar
  7. 7.
    Weinberger T, Annunziato R, Riklin E, Shemesh E, Sicherer SH. A randomized controlled trial to reduce food allergy anxiety about casual exposure by holding the allergen: TOUCH study. J Allergy Clin Immunol Pract. 2019;7(6):2039–42.e14.  https://doi.org/10.1016/j.jaip.2019.01.018.CrossRefPubMedGoogle Scholar
  8. 8.
    Wang J, Bingemann T, Russell AF, Young MC, Sicherer SH. The allergist’s role in anaphylaxis and food allergy management in the school and childcare setting. J Allergy Clin Immunol Pract. 2018;6(2):427–35.  https://doi.org/10.1016/j.jaip.2017.11.022.CrossRefPubMedGoogle Scholar
  9. 9.
    Lieberman JA, Weiss C, Furlong TJ, Sicherer M, Sicherer SH. Bullying among pediatric patients with food allergy. Ann Allergy Asthma Immunol. 2010;105(4):282–6.  https://doi.org/10.1016/j.anai.2010.07.011.CrossRefPubMedGoogle Scholar
  10. 10.
    • Baumert JL, Taylor SL, Koppelman SJ. Quantitative assessment of the safety benefits associated with increasing clinical peanut thresholds through immunotherapy. J Allergy Clin Immunol Pract. 2018;6(2):457–65.e4.  https://doi.org/10.1016/j.jaip.2017.05.006 Model of US food consumption data and estimated peanut contamination suggesting protective peanut threshold. CrossRefPubMedGoogle Scholar
  11. 11.
    Remington BC, Krone T, Koppelman SJ. Quantitative risk reduction through peanut immunotherapy: safety benefits of an increased threshold in Europe. Pediatr Allergy Immunol. 2018;29(7):762–72.  https://doi.org/10.1111/pai.12961.CrossRefPubMedGoogle Scholar
  12. 12.
    Jones SM, Agbotounou WK, Fleischer DM, Burks AW, Pesek RD, Harris MW, et al. Safety of epicutaneous immunotherapy for the treatment of peanut allergy: a phase 1 study using the Viaskin patch. J Allergy Clin Immunol. 2016;137(4):1258–61.e10.  https://doi.org/10.1016/j.jaci.2016.01.008.CrossRefPubMedGoogle Scholar
  13. 13.
    • Jones SM, Sicherer SH, Burks AW, Leung DYM, Lindblad RW, Dawson P, et al. Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults. J Allergy Clin Immunol. 2017;139(4):1242–52.e9.  https://doi.org/10.1016/j.jaci.2016.08.017 Phase 2b study of peanut patch. CrossRefPubMedGoogle Scholar
  14. 14.
    • Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, et al. Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: a randomized clinical trial. JAMA. 2017;318(18):1798–809.  https://doi.org/10.1001/jama.2017.16591 Phase 2b study of peanut patch. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    •• Fleischer DM, Greenhawt M, Sussman G, Begin P, Nowak-Wegrzyn A, Petroni D, et al. Effect of epicutaneous immunotherapy vs placebo on reaction to peanut protein ingestion among children with peanut allergy: the PEPITES randomized clinical trial. JAMA. 2019.  https://doi.org/10.1001/jama.2019.1113 Phase 3 study of peanut patch.CrossRefGoogle Scholar
  16. 16.
    Kim EH, Bird JA, Kulis M, Laubach S, Pons L, Shreffler W, et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol. 2011;127(3):640–6.e1.  https://doi.org/10.1016/j.jaci.2010.12.1083.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, et al. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013;131(1):119–27.e1–7.  https://doi.org/10.1016/j.jaci.2012.11.011.CrossRefPubMedGoogle Scholar
  18. 18.
    Chin SJ, Vickery BP, Kulis MD, Kim EH, Varshney P, Steele P, et al. Sublingual versus oral immunotherapy for peanut-allergic children: a retrospective comparison. J Allergy Clin Immunol. 2013;132(2):476–8.e2.  https://doi.org/10.1016/j.jaci.2013.02.017.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2015;135(5):1275–82.e1–6.  https://doi.org/10.1016/j.jaci.2014.11.005.CrossRefPubMedGoogle Scholar
  20. 20.
    • Bindslev-Jensen C, de Kam P-J, van Twuijver E, Boot DB, El Galta R, Mose AP, et al. SCIT-treatment with a chemically modified, aluminum hydroxide adsorbed peanut extract (HAL-MPE1) was generally safe and well tolerated and showed immunological changes in peanut allergic patients. J Allergy Clin Immunol. 2017;139(2, Supplement):AB191.  https://doi.org/10.1016/j.jaci.2016.12.623 Phase 1 safety study of recombinant peanut vaccine HAL-MPE1. CrossRefGoogle Scholar
  21. 21.
    Li X-M, Song Y, Su Y, Heiland T, Sampson HA. Immunization with ARA h1,2,3-LAMP-Vax peanut vaccine blocked IgE mediated-anaphylaxis in a peanut allergic murine model. J Allergy Clin Immunol. 2015;135(2):AB167.  https://doi.org/10.1016/j.jaci.2014.12.1482.CrossRefGoogle Scholar
  22. 22.
    Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165–7.  https://doi.org/10.1016/j.jaci.2010.02.029.CrossRefPubMedGoogle Scholar
  23. 23.
    Rutault K, Agbotounou W, Peillon A, Thébault C, Vincent F, Martin L, et al. Safety of Viaskin milk epicutaneous immunotherapy (EPIT) in IgE-mediated cow’s milk allergy (CMA) in children (MILES study). J Allergy Clin Immunol. 2016;137(2):AB132.  https://doi.org/10.1016/j.jaci.2015.12.566.CrossRefGoogle Scholar
  24. 24.
    de Boissieu D, Dupont C. Sublingual immunotherapy for cow’s milk protein allergy: a preliminary report. Allergy. 2006;61(10):1238–9.  https://doi.org/10.1111/j.1398-9995.2006.01196.x.CrossRefPubMedGoogle Scholar
  25. 25.
    Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129(2):448–55, 55.e1–5.  https://doi.org/10.1016/j.jaci.2011.10.023.CrossRefPubMedGoogle Scholar
  26. 26.
    Vallery-Radot P, Hangenau J. Asthme d’origine equine. Essai de desensibilisation par des cutireactions repetees. Bull Soc Med Hop Paris. 1921;45:1251–60.Google Scholar
  27. 27.
    Wang J, Sampson HA. Safety and efficacy of epicutaneous immunotherapy for food allergy. Pediatr Allergy Immunol. 2018;29(4):341–9.  https://doi.org/10.1111/pai.12869.CrossRefPubMedGoogle Scholar
  28. 28.
    Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest. 1992;90(2):482–7.  https://doi.org/10.1172/jci115884.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Brough HA, Liu AH, Sicherer S, Makinson K, Douiri A, Brown SJ, et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol. 2015;135(1):164–70.  https://doi.org/10.1016/j.jaci.2014.10.007.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Venkataraman D, Soto-Ramirez N, Kurukulaaratchy RJ, Holloway JW, Karmaus W, Ewart SL, et al. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J Allergy Clin Immunol. 2014;134(4):876–82.e4.  https://doi.org/10.1016/j.jaci.2014.07.033.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Mondoulet L, Dioszeghy V, Puteaux E, Ligouis M, Dhelft V, Letourneur F, et al. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice. Clin Transl Allergy. 2012;2(1):22.  https://doi.org/10.1186/2045-7022-2-22.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH. Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy. 2010;40(4):659–67.  https://doi.org/10.1111/j.1365-2222.2009.03430.x.CrossRefPubMedGoogle Scholar
  33. 33.
    Dioszeghy V, Mondoulet L, Laoubi L, Dhelft V, Plaquet C, Bouzereau A, et al. Antigen uptake by Langerhans cells is required for the induction of regulatory T cells and the acquisition of tolerance during epicutaneous immunotherapy in OVA-sensitized mice. Front Immunol. 2018;9:1951.  https://doi.org/10.3389/fimmu.2018.01951.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J Immunol (Baltimore, Md : 1950). 2011;186(10):5629–37.  https://doi.org/10.4049/jimmunol.1003134.CrossRefGoogle Scholar
  35. 35.
    Tordesillas L, Mondoulet L, Blazquez AB, Benhamou PH, Sampson HA, Berin MC. Epicutaneous immunotherapy induces gastrointestinal LAP(+) regulatory T cells and prevents food-induced anaphylaxis. J Allergy Clin Immunol. 2017;139(1):189–201.e4.  https://doi.org/10.1016/j.jaci.2016.03.057.CrossRefPubMedGoogle Scholar
  36. 36.
    Dioszeghy V, Mondoulet L, Puteaux E, Dhelft V, Ligouis M, Plaquet C, et al. Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut. Cell Mol Immunol. 2017;14(9):770–82.  https://doi.org/10.1038/cmi.2016.14.CrossRefPubMedGoogle Scholar
  37. 37.
    Mondoulet L, Dioszeghy V, Vanoirbeek JA, Nemery B, Dupont C, Benhamou PH. Epicutaneous immunotherapy using a new epicutaneous delivery system in mice sensitized to peanuts. Int Arch Allergy Immunol. 2011;154(4):299–309.  https://doi.org/10.1159/000321822.CrossRefPubMedGoogle Scholar
  38. 38.
    Remington B, Krone T, Koppelman S. Quantitative risk reduction through epicutaneous immunotherapy (EPIT): results from the PEPITES phase III trial. Ann Allergy Asthma Immunol. 2018;121(5):S11.  https://doi.org/10.1016/j.anai.2018.09.032.CrossRefGoogle Scholar
  39. 39.
    Mondoulet L, Dioszeghy V, Larcher T, Ligouis M, Dhelft V, Puteaux E, et al. Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice. PLoS One. 2012;7(2):e31967-e.  https://doi.org/10.1371/journal.pone.0031967.CrossRefGoogle Scholar
  40. 40.
    Mondoulet L, Kalach N, Dhelft V, Larcher T, Delayre-Orthez C, Benhamou PH, et al. Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts. Clin Exp Allergy. 2017;47(12):1640–7.  https://doi.org/10.1111/cea.13037.CrossRefPubMedGoogle Scholar
  41. 41.
    Spergel JM, Elci OU, Muir AB, Liacouras CA, Wilkins BJ, Burke D, et al. Efficacy of epicutaneous immunotherapy in children with milk-induced eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2019.  https://doi.org/10.1016/j.cgh.2019.05.014.
  42. 42.
    Cox LS. Sublingual immunotherapy: historical perspective and practical guidance. J Allergy Clin Immunol Pract. 2017;5(1):63–5.  https://doi.org/10.1016/j.jaip.2016.11.016.CrossRefPubMedGoogle Scholar
  43. 43.
    Mahler V, Esch RE, Kleine-Tebbe J, Lavery WJ, Plunkett G, Vieths S, et al. Understanding differences in allergen immunotherapy products and practices in North America and Europe. J Allergy Clin Immunol. 2019;143(3):813–28.  https://doi.org/10.1016/j.jaci.2019.01.024.CrossRefPubMedGoogle Scholar
  44. 44.
    Jay DC, Nadeau KC. Immune mechanisms of sublingual immunotherapy. Curr Allergy Asthma Rep. 2014;14(11):473.  https://doi.org/10.1007/s11882-014-0473-1.CrossRefPubMedGoogle Scholar
  45. 45.
    Marcucci F, Incorvaia C, Sensi L, Di Cara G, Cadario G, Cavaliere A, et al. Lack of inflammatory cells in the oral mucosa of subjects undergoing sublingual immunotherapy. Int J Immunopathol Pharmacol. 2008;21(3):609–13.  https://doi.org/10.1177/039463200802100314.CrossRefPubMedGoogle Scholar
  46. 46.
    Fujita H, Soyka MB, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy. 2012;2(1):2.  https://doi.org/10.1186/2045-7022-2-2.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Akdis CA, Barlan IB, Bahceciler N, Akdis M. Immunological mechanisms of sublingual immunotherapy. Allergy. 2006;61(Suppl 81):11–4.  https://doi.org/10.1111/j.1398-9995.2006.01159.x.CrossRefPubMedGoogle Scholar
  48. 48.
    Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R, et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116(5):1073–9.  https://doi.org/10.1016/j.jaci.2005.08.027.CrossRefPubMedGoogle Scholar
  49. 49.
    Cafone J, Capucilli P, Hill DA, Spergel JM. Eosinophilic esophagitis during sublingual and oral allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2019.  https://doi.org/10.1097/aci.0000000000000537.CrossRefGoogle Scholar
  50. 50.
    Lawrence MG, Steinke JW, Borish L. Basic science for the clinician: mechanisms of sublingual and subcutaneous immunotherapy. Ann Allergy Asthma Immunol. 2016;117(2):138–42.  https://doi.org/10.1016/j.anai.2016.06.027.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    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):S1–55.  https://doi.org/10.1016/j.jaci.2010.09.034.CrossRefPubMedGoogle Scholar
  52. 52.
    Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992;90(2):256–62.CrossRefGoogle Scholar
  53. 53.
    Nelson HS, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol. 1997;99(6 Pt 1):744–51.CrossRefGoogle Scholar
  54. 54.
    Wood RA, Sicherer SH, Burks AW, Grishin A, Henning AK, Lindblad R, et al. A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. Allergy. 2013;68(6):803–8.  https://doi.org/10.1111/all.12158.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Feuille E, Nowak-Wegrzyn A. Allergen-specific immunotherapies for food allergy. Allergy, Asthma Immunol Res. 2018;10(3):189–206.  https://doi.org/10.4168/aair.2018.10.3.189.CrossRefGoogle Scholar
  56. 56.
    Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med. 2000;192(9):1213–22.  https://doi.org/10.1084/jem.192.9.1213.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    van der Kleij HPM, Warmenhoven HJM, van Ree R, Versteeg SA, Pieters RHH, Dreskin SC, et al. Chemically modified peanut extract shows increased safety while maintaining immunogenicity. Allergy. 2018.  https://doi.org/10.1111/all.13687.CrossRefGoogle Scholar
  58. 58.
    Palmer GW, Dibbern DA Jr, Burks AW, Bannon GA, Bock SA, Porterfield HS, et al. Comparative potency of Ara h 1 and Ara h 2 in immunochemical and functional assays of allergenicity. Clin Immunol (Orlando, Fla). 2005;115(3):302–12.  https://doi.org/10.1016/j.clim.2005.02.011.CrossRefGoogle Scholar
  59. 59.
    Porterfield HS, Murray KS, Schlichting DG, Chen X, Hansen KC, Duncan MW, et al. Effector activity of peanut allergens: a critical role for Ara h 2, Ara h 6, and their variants. Clin Exp Allergy. 2009;39(7):1099–108.  https://doi.org/10.1111/j.1365-2222.2009.03273.x.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Kulis M, Chen X, Lew J, Wang Q, Patel OP, Zhuang Y, et al. The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice. Clin Exp Allergy. 2012;42(2):326–36.  https://doi.org/10.1111/j.1365-2222.2011.03934.x.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Chen X, Wang Q, El-Mezayen R, Zhuang Y, Dreskin SC. Ara h 2 and Ara h 6 have similar allergenic activity and are substantially redundant. Int Arch Allergy Immunol. 2013;160(3):251–8.  https://doi.org/10.1159/000341642.CrossRefPubMedGoogle Scholar
  62. 62.
    Wilcock LK, Francis JN, Durham SR. Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells. Clin Exp Allergy. 2004;34(9):1373–8.  https://doi.org/10.1111/j.1365-2222.2004.02052.x.CrossRefPubMedGoogle Scholar
  63. 63.
    Tang DC, DeVit M, Johnston SA. Genetic immunization is a simple method for eliciting an immune response. Nature. 1992;356(6365):152–4.  https://doi.org/10.1038/356152a0.CrossRefPubMedGoogle Scholar
  64. 64.
    Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993;259(5102):1745–9.  https://doi.org/10.1126/science.8456302.CrossRefPubMedGoogle Scholar
  65. 65.
    Liu MA. DNA vaccines: an historical perspective and view to the future. Immunol Rev. 2011;239(1):62–84.  https://doi.org/10.1111/j.1600-065X.2010.00980.x.CrossRefPubMedGoogle Scholar
  66. 66.
    Su Y, Connolly M, Marketon A, Heiland T. CryJ-LAMP DNA vaccines for Japanese red cedar allergy induce robust Th1-type immune responses in murine model. J Immunol Res. 2016;2016:4857869.  https://doi.org/10.1155/2016/4857869.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Su Y, Romeu-Bonilla E, Anagnostou A, Fitz-Patrick D, Hearl W, Heiland T. Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: a phase I study. Hum Vaccin Immunother. 2017;13(12):2804–13.  https://doi.org/10.1080/21645515.2017.1329070.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Gunawardana NC, Durham SR. New approaches to allergen immunotherapy. Ann Allergy Asthma Immunol. 2018;121(3):293–305.  https://doi.org/10.1016/j.anai.2018.07.014.CrossRefPubMedGoogle Scholar
  69. 69.
    Johnson-Weaver BT, Staats HF, Burks AW, Kulis MD. Adjuvanted immunotherapy approaches for peanut allergy. Front Immunol. 2018;9:2156.  https://doi.org/10.3389/fimmu.2018.02156.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Kramer MF, Heath MD. Aluminium in allergen-specific subcutaneous immunotherapy--a German perspective. Vaccine. 2014;32(33):4140–8.  https://doi.org/10.1016/j.vaccine.2014.05.063.CrossRefPubMedGoogle Scholar
  71. 71.
    Jensen-Jarolim E. Aluminium in allergies and allergen immunotherapy. World Allergy Organ J. 2015;8(1):7.  https://doi.org/10.1186/s40413-015-0060-5.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hong S-J, Michael JG, Fehringer A, Leung DYM. Pepsin-digested peanut contains T-cell epitopes but no IgE epitopes. J Allergy Clin Immunol. 1999;104(2):473–7.  https://doi.org/10.1016/S0091-6749(99)70396-9.CrossRefPubMedGoogle Scholar
  73. 73.
    Li S, Li X, Burks A, Bannon G, Sampson H. Modulation of peanut allergy by peptide-based immunotherapy. J Allergy Clin Immunol. 2001;107(2).Google Scholar
  74. 74.
    Prickett SR, Voskamp AL, Dacumos-Hill A, Symons K, Rolland JM, O’Hehir RE. Ara h 2 peptides containing dominant CD4+ T-cell epitopes: candidates for a peanut allergy therapeutic. J Allergy Clin Immunol. 2011;127(3):608–15.e5.  https://doi.org/10.1016/j.jaci.2010.09.027.CrossRefPubMedGoogle Scholar
  75. 75.
    Kulis M, MacQueen I, Li Y, Guo R, Zhong X-P, Burks AW. Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy. J Allergy Clin Immunol. 2012;130(3):716–23.  https://doi.org/10.1016/j.jaci.2012.05.044.CrossRefPubMedGoogle Scholar
  76. 76.
    Shen W, Marketon A, Su Y, Macauley J, Heiland T. Development of LAMP-based vaccine for cashew allergy immunotherapy. J Immunol. 2016;196(1 Supplement):215.8–.8.Google Scholar
  77. 77.
    Greenhawt M, Marsh R, Gilbert H, Sicherer S, DunnGalvin A, Matlock D. Understanding caregiver goals, benefits, and acceptable risks of peanut allergy therapies. Ann Allergy Asthma Immunol. 2018;121(5):575–9.  https://doi.org/10.1016/j.anai.2018.06.018.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pediatric Allergy & Immunology, Department of PediatricsElliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations