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Potency of T-Cell Epitope-Based Peptide Vaccines in Food Allergy Treatment

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Nutrition and Immunity

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Abstract

The prevalence of food allergy is increasing with cow’s milk and peanut being major culprit foods, particularly in young children. Currently, only allergen avoidance or drugs that aid symptom relief are available for food allergy treatment. As allergen immunotherapy (AIT) is the only treatment that really tackles the cause of allergy, there is an urgent need for improved cow’s milk and peanut-specific AIT. Although AIT with whole allergen extracts is already used for the treatment of allergies to many aeroallergens, its potential for food allergy treatment is often questioned due to safety, efficacy, and compliance issues of these conventional types of AIT. Based on the central role of T cells in orchestrating allergic responses, AIT with T-cell epitope-based peptide vaccines may provide a better alternative in treating peanut allergy than conventional AIT with whole allergen extracts. These peptide vaccines comprise allergen peptides that consist of dominant T-cell epitopes that are too short to cross-link mast cell-bound allergen-specific immunoglobulin (Ig) E antibodies. Therefore, these vaccines are considered unable to induce adverse allergic responses. The aim of this literature review is to assess the potency of peptide-based immunotherapy in cow’s milk and peanut allergy treatment by focusing on its safety, efficacy, underlying immunological mechanisms of action, and practical applicability. Peptide vaccine treatment influences T-cell polarization by establishing alterations at the level of interacting immune cells upon allergen exposure. There are four major potential underlying mechanisms by which these altered immune cell interactions favor tolerance induction. These mechanisms are indicated to be an immune deviation, anergy, deletion, and active suppression. Peptide vaccine treatment alters immune cell interactions in such a way that tolerance is induced. These vaccines establish these altered interactions by their characteristic physical form, their tolerance-favoring route of administration, and high-dose allergen exposure. The results of trials focusing on peptide vaccine treatment are truly encouraging. Nevertheless, further research is needed to evaluate whether these results are of predictive value for the potency of these peptide vaccines in allergy treatment. Much of what has been learned about peptide vaccines in cow’s milk and peanut allergy can be applied in the treatment of other food allergies with severe allergic manifestation, like tree nuts and fish and shellfish allergies. Although peptide-based AIT has the potential for treating food-allergic individuals in the future, strict avoidance of allergens remains the standard approach for food allergy management for now.

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References

  1. Wells HG. Studies on the chemistry of anaphylaxis (III). Experiments with isolated proteins, especially those of the hen’s egg. J Infect Dis. 1911;9:147–71.

    Article  CAS  Google Scholar 

  2. Chase MW. Inhibition of experimental drug allergy by prior feeding of the sensitizing agent. Proc Soc Exp Biol Med. 1946;61(3):257–9.

    Article  CAS  PubMed  Google Scholar 

  3. Burks AW, Laubach S, Jones SM. Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol. 2008;121(6):1344–50.

    Article  CAS  PubMed  Google Scholar 

  4. Weiner HL, da Cunha AP, Quintana F, Wu H. Oral tolerance. Immunol Rev. 2011;241(1):241–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Berin MC, Sampson HA. Food allergy: an enigmatic epidemic. Trends Immunol. 2013;34(8):390–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. Philadelphia: Elsevier Health Sciences; 2014.

    Google Scholar 

  7. Wieder E. Dendritic cells: a basic review. International Society for Cellular Therapy. 2003.

    Google Scholar 

  8. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu Y-J, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18(1):767–811.

    Article  CAS  PubMed  Google Scholar 

  9. Perdijk O, van Neerven RJ, Meijer B, Savelkoul HF, Brugman S. Induction of human tolerogenic dendritic cells by 3’-sialyllactose via TLR4 is explained by LPS contamination. Glycobiology. 2018;28:126–30.

    Article  CAS  PubMed  Google Scholar 

  10. Martínez-Borra J, López-Larrea C. The emergence of the major histocompatilibility complex. In: Self and nonself. New York: Springer; 2012. p. 277–89.

    Chapter  Google Scholar 

  11. Grewal IS, Flavell RA. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev. 1996;153(1):85–106.

    Article  CAS  PubMed  Google Scholar 

  12. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Salomon BT, Bluestone JA. Cutting edge: LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. J Immunol. 1998;161(10):5138–42.

    CAS  PubMed  Google Scholar 

  15. Stutman O, Cells T. Contemporary topics in immunobiology, vol. 7. New York: Plenum Press; 1977. p. 1–386.

    Book  Google Scholar 

  16. Curtsinger JM, Mescher MF. Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol. 2010;22(3):333–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cala CM, Moseley CE, Steele C, Dowdy SM, Cutter GR, Ness JM, et al. T cell cytokine signatures: biomarkers in pediatric multiple sclerosis. J Neuroimmunol. 2016;297:1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Conrad ML, Renz H, Blaser K. Immunological approaches for tolerance induction in allergy. In: Vaccines against allergies. Berlin: Springer; 2011. p. 1–26.

    Google Scholar 

  19. Jutel M, Akdis M, Blaser K, Akdis C. Mechanisms of allergen specific immunotherapy–T-cell tolerance and more. Allergy. 2006;61(7):796–807.

    Article  CAS  PubMed  Google Scholar 

  20. Valenta R, Coffman RL. Vaccines against allergies. Berlin: Springer; 2011.

    Book  Google Scholar 

  21. Gregory JA, Shepley-McTaggart A, Umpierrez M, Hurlburt BK, Maleki SJ, Sampson HA, et al. Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice. Plant Biotechnol J. 2016;14:1541–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Anagnostou K. Recent advances in immunotherapy and vaccine development for peanut allergy. Ther Adv Vaccines. 2015;3(3):55–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. O’Hehir RE, Prickett SR, Rolland JM. T cell epitope peptide therapy for allergic diseases. Curr Allergy Asthma Rep. 2016;16(2):1–9.

    Article  CAS  Google Scholar 

  24. Commins SP, Kim EH, Orgel K, Kulis M. Peanut allergy: new developments and clinical implications. Curr Allergy Asthma Rep. 2016;16(5):1–6.

    Article  CAS  Google Scholar 

  25. Avery NJ, King RM, Knight S, Hourihane JOB. Assessment of quality of life in children with peanut allergy. Pediatr Allergy Immunol. 2003;14(5):378–82.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. Bublin M, Breiteneder H. Developing therapies for peanut allergy. Int Arch Allergy Immunol. 2014;165(3):179–94.

    Article  CAS  PubMed  Google Scholar 

  28. Stahl MC, Rans TS. Potential therapies for peanut allergy. Ann Allergy Asthma Immunol. 2011;106(3):179–87.

    Article  CAS  PubMed  Google Scholar 

  29. Ramesh M, Yuenyongviwat A, Konstantinou GN, Lieberman J, Pascal M, Masilamani M, et al. Peanut T-cell epitope discovery: Ara h 1. J Allergy Clin Immunol. 2016;137:1764–1771.e4.

    Article  CAS  PubMed  Google Scholar 

  30. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 5th ed. New York: Garland Science; 2007. Search PubMed 2002:813–78.

    Book  Google Scholar 

  31. Worbs T, Bode U, Yan S, Hoffmann MW, Hintzen G, Bernhardt G, et al. Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med. 2006;203(3):519–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Valenta R, Hochwallner H, Linhart B, Pahr S. Food allergies: the basics. Gastroenterology. 2015;148(6):1120–31.e4.

    Article  CAS  PubMed  Google Scholar 

  33. Nowak-Wegrzyn A. Food allergy to proteins. 2007.

    Book  Google Scholar 

  34. Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454(7203):445–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ali FR, Kay AB, Larché M. The potential of peptide immunotherapy in allergy and asthma. Curr Allergy Asthma Rep. 2002;2(2):151–8.

    Article  PubMed  Google Scholar 

  36. Saarinen KM, Pelkonen AS, Mäkelä MJ, Savilahti E. Clinical course and prognosis of cow’s milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol. 2005;116(4):869–75.

    Article  CAS  PubMed  Google Scholar 

  37. Vanto T, Helppilä S, Juntunen-Backman K, Kalimo K, Klemola T, Korpela R, et al. Prediction of the development of tolerance to milk in children with cow's milk hypersensitivity. J Pediatr. 2004;144(2):218–22.

    Article  PubMed  Google Scholar 

  38. Høst A, Halken S, Jacobsen HP, Christensen AE, Herskind AM, Plesner K. Clinical course of cow’s milk protein allergy/intolerance and atopic diseases in childhood. Pediatr Allergy Immunol. 2002;13(s15):23–8.

    Article  PubMed  Google Scholar 

  39. Venter C, Arshad SH. Epidemiology of food allergy. Pediatr Clin. 2011;58(2):327–49.

    Google Scholar 

  40. Lam HY, Van Hoffen E, Michelsen A, Guikers K, Van Der Tas C, Bruijnzeel-Koomen C, et al. Cow’s milk allergy in adults is rare but severe: both casein and whey proteins are involved. Clin Exp Allergy. 2008;38(6):995–1002.

    Article  PubMed  Google Scholar 

  41. Crittenden RG, Bennett LE. Cow’s milk allergy: a complex disorder. J Am Coll Nutr. 2005;24(sup6):582S–91S.

    Article  CAS  PubMed  Google Scholar 

  42. Fiocchi A, Schünemann HJ, Brozek J, Restani P, Beyer K, Troncone R, et al. Diagnosis and rationale for action against cow’s milk allergy (DRACMA): a summary report. J Allergy Clin Immunol. 2010;126(6):1119–28.e12.

    Article  PubMed  Google Scholar 

  43. Koletzko S, Niggemann B, Arató A, Dias J, Heuschkel R, Husby S, et al. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 2012;55(2):221–9.

    Article  CAS  PubMed  Google Scholar 

  44. Wal JM. Cow’s milk allergens. Allergy. 1998;53(11):1013–22.

    Article  CAS  PubMed  Google Scholar 

  45. Restani P, Ballabio C, Di Lorenzo C, Tripodi S, Fiocchi A. Molecular aspects of milk allergens and their role in clinical events. Anal Bioanal Chem. 2009;395(1):47–56.

    Article  CAS  PubMed  Google Scholar 

  46. Shek L, Bardina L, Castro R, Sampson H, Beyer K. Humoral and cellular responses to cow milk proteins in patients with milk-induced IgE-mediated and non-IgE-mediated disorders. Allergy. 2005;60(7):912–9.

    Article  CAS  PubMed  Google Scholar 

  47. Boyano-Martínez T, García-Ara C, Pedrosa M, Díaz-Pena JM, Quirce S. Accidental allergic reactions in children allergic to cow’s milk proteins. J Allergy Clin Immunol. 2009;123(4):883–8.

    Article  PubMed  CAS  Google Scholar 

  48. Jansson S-A, Heibert-Arnlind M, Middelveld RJ, Bengtsson UJ, Sundqvist A-C, Kallström-Bengtsson I, et al. Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods. Clin Transl Allergy. 2013;3(1):21.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wassenberg J, Cochard MM, DunnGalvin A, Ballabeni P, Flokstra-de Blok BM, Newman CJ, et al. Parent perceived quality of life is age-dependent in children with food allergy. Pediatr Allergy Immunol. 2012;23(5):412–9.

    Article  PubMed  Google Scholar 

  50. Yeung JP, Kloda LA, McDevitt J, Ben-Shoshan M, Alizadehfar R. Oral immunotherapy for milk allergy. Cochrane Database Syst Rev. 2012:11.

    Google Scholar 

  51. Exl B-M, Fritsché R. Cow’s milk protein allergy and possible means for its prevention. Nutrition. 2001;17(7):642–51.

    Article  CAS  PubMed  Google Scholar 

  52. Zeiger RS. Food allergen avoidance in the prevention of food allergy in infants and children. Pediatrics. 2003;111(Supplement 3):1662–71.

    PubMed  Google Scholar 

  53. Hays T, Wood RA. A systematic review of the role of hydrolyzed infant formulas in allergy prevention. Arch Pediatr Adolesc Med. 2005;159(9):810–6.

    Article  PubMed  Google Scholar 

  54. Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121(1):183–91.

    Article  PubMed  Google Scholar 

  55. Commission directive 2006/141/EC of 22 december 2006 on infant formula and follow-on formula and amending directive 1999/21/EC. Official Journal of the European Union. 2006;L 401:1-33.

    Google Scholar 

  56. Metcalfe J, Prescott SL, Palmer DJ. Randomized controlled trials investigating the role of allergen exposure in food allergy: where are we now? Curr Opin Allergy Clin Immunol. 2013;13(3):296–305.

    Article  CAS  PubMed  Google Scholar 

  57. Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122(5):984–91.

    Article  PubMed  CAS  Google Scholar 

  58. Poole JA, Barriga K, Leung DY, Hoffman M, Eisenbarth GS, Rewers M, et al. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics. 2006;117(6):2175–82.

    Article  PubMed  Google Scholar 

  59. Arshad SH, Matthews S, Gant C, Hide D. Effect of allergen avoidance on development of allergic disorders in infancy. The Lancet. 1992;339(8808):1493–7.

    Article  CAS  Google Scholar 

  60. Zeiger RS, Heller S, Mellon MH, Forsythe AB, O’Connor RD, Hamburger RN, et al. Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study. J Allergy Clin Immunol. 1989;84(1):72–89.

    Article  CAS  PubMed  Google Scholar 

  61. van Esch BC, Schouten B, de Kivit S, Hofman GA, Knippels LM, Willemsen LE, et al. Oral tolerance induction by partially hydrolyzed whey protein in mice is associated with enhanced numbers of Foxp3+ regulatory T-cells in the mesenteric lymph nodes. Pediatr Allergy Immunol. 2011;22(8):820–6.

    Article  PubMed  Google Scholar 

  62. Peng HJ, Su SN, Tsai JJ, Tsai LC, Kuo HL, Kuo SW. Effect of ingestion of cow’s milk hydrolysed formulas on whey protein-specific Th2 immune responses in naïve and sensitized mice. Clin Exp Allergy. 2004;34(4):663–70.

    Article  CAS  PubMed  Google Scholar 

  63. Fritsché R, Pahud JJ, Pecquet S, Pfeifer A. Induction of systemic immunologic tolerance to β-lactoglobulin by oral administration of a whey protein hydrolysate. J Allergy Clin Immunol. 1997;100(2):266–73.

    Article  PubMed  Google Scholar 

  64. Iskedjian M, Szajewska H, Spieldenner J, Farah B, Berbari J. Meta-analysis of a partially hydrolysed 100%-whey infant formula vs. extensively hydrolysed infant formulas in the prevention of atopic dermatitis. Curr Med Res Opin. 2010;26(11):2599–606.

    Article  CAS  PubMed  Google Scholar 

  65. Osborn DA, Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. 2003:4.

    Google Scholar 

  66. Halken S, Hansen KS, Jacobsen HP, Estmann A, Christensen AEF, Hansen LG, et al. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Pediatr Allergy Immunol. 2000;11(3):149–61.

    Article  CAS  PubMed  Google Scholar 

  67. Halken S, Høst A, Hansen LG, Østerballe O. Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study. Pediatr Allergy Immunol. 1993;4(4):173–81.

    Article  CAS  PubMed  Google Scholar 

  68. Brożek J, Terracciano L, Hsu J, Kreis J, Compalati E, Santesso N, et al. Oral immunotherapy for IgE-mediated cow’s milk allergy: a systematic review and meta-analysis. Clin Exp Allergy. 2012;42(3):363–74.

    Article  PubMed  CAS  Google Scholar 

  69. Fleischer DM. The natural history of peanut and tree nut allergy. Curr Allergy Asthma Rep. 2007;7(3):175–81.

    Article  CAS  PubMed  Google Scholar 

  70. Sampson HA. Peanut allergy. N Engl J Med. 2002;346(17):1294–9.

    Article  PubMed  Google Scholar 

  71. Sicherer SH, Wood RA, Stablein D, Lindblad R, Burks AW, Liu AH, et al. Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants. J Allergy Clin Immunol. 2010;126(6):1191–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mayer ML, Sandborg CI, Mellins ED. Role of pediatric and internist rheumatologists in treating children with rheumatic diseases. Pediatrics. 2004;113(3):e173–e81.

    Article  PubMed  Google Scholar 

  73. Wang J, Sampson HA. Treatments for food allergy: how close are we? Immunol Res. 2012;54(1–3):83–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Chelladurai Y, Suarez-Cuervo C, Erekosima N, Kim JM, Ramanathan M, Segal JB, et al. Effectiveness of subcutaneous versus sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. J Allergy Clin Immunol Pract. 2013;1(4):361–9.

    Article  PubMed  Google Scholar 

  75. Pauli G, Malling H-J. Allergen-specific immunotherapy with recombinant allergens. In: Vaccines against allergies. Berlin: Springer; 2011. p. 43–54.

    Chapter  Google Scholar 

  76. Anagnostou K, Clark A. Peanut immunotherapy. Clin Transl Allergy. 2014;4:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Yee CS, Rachid R. The heterogeneity of oral immunotherapy clinical trials: implications and future directions. Curr Allergy Asthma Rep. 2016;16(4):1–19.

    Article  CAS  Google Scholar 

  78. Bauer CS, Rank MA. Comparative efficacy and safety of subcutaneous versus sublingual immunotherapy. J Allergy Clin Immunol. 2014;134(3):765.

    Article  PubMed  Google Scholar 

  79. Prickett S, Rolland J, O’Hehir R. Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy. Clin Exp Allergy. 2015;45(6):1015–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Moldaver D, Larché M. Immunotherapy with peptides. Allergy. 2011;66(6):784–91.

    Article  CAS  PubMed  Google Scholar 

  81. Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J Allergy Clin Immunol. 2004;113(6):1025–34.

    Article  CAS  PubMed  Google Scholar 

  82. Gorelik M, Narisety SD, Guerrerio AL, Chichester KL, Keet CA, Bieneman AP, et al. Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol. 2015;135(5):1283–92.

    Article  CAS  PubMed  Google Scholar 

  83. Kiel MA, Röder E, van Wijk RG, Al MJ, Hop WC, Rutten-van Mölken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132(2):353–60.e2.

    Article  PubMed  Google Scholar 

  84. De Leon MP, Rolland JM, O’Hehir RE. The peanut allergy epidemic: allergen molecular characterisation and prospects for specific therapy. Expert Rev Mol Med. 2007;9(01):1–18.

    Article  PubMed  Google Scholar 

  85. Vila L, Beyer K, Järvinen KM, Chatchatee P, Bardina L, Sampson H. Role of conformational and linear epitopes in the achievement of tolerance in cow’s milk allergy. Clin Exp Allergy. 2001;31(10):1599–606.

    Article  CAS  PubMed  Google Scholar 

  86. Cromwell O, Niederberger V, Horak F, Fiebig H. Clinical experience with recombinant molecules for allergy vaccination. In: Vaccines against allergies. Berlin: Springer; 2011. p. 27–42.

    Chapter  Google Scholar 

  87. Larche M. Peptide immunotherapy for allergic diseases. Allergy. 2007;62(3):325–31.

    Article  CAS  PubMed  Google Scholar 

  88. Murphy KM, Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol. 2010;11(8):674–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wedderburn LR, O’Hehir RE, Hewitt C, Lamb JR, Owen MJ. In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens. Proc Natl Acad Sci. 1993;90(17):8214–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. O’hehir R, Lake R, Schall T, Yssel H, Panagiotopoulou E, Lamb J. Regulation of cytokine and chemokine transcription in a human TH2 type T-cell clone during the induction phase of anergy. Clin Exp Allergy. 1996;26(1):20–7.

    Article  PubMed  Google Scholar 

  91. Lamb JR, Skidmore BJ, Green N, Chiller JM, Feldmann M. Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med. 1983;157(5):1434–47.

    Article  CAS  PubMed  Google Scholar 

  92. Kearney ER, Pape KA, Loh DY, Jenkins MK. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity. 1994;1(4):327–39.

    Article  CAS  PubMed  Google Scholar 

  93. Groux H, Bigler M, De Vries J, Roncarolo M-G. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med. 1996;184(1):19–29.

    Article  CAS  PubMed  Google Scholar 

  94. Haselden BM, Kay AB, Larché M. Peptide-mediated immune responses in specific immunotherapy. Int Arch Allergy Immunol. 2000;122(4):229–37.

    Article  CAS  PubMed  Google Scholar 

  95. Pipet A, Botturi K, Pinot D, Vervloet D, Magnan A. Allergen-specific immunotherapy in allergic rhinitis and asthma. Mechanisms and proof of efficacy. Respir Med. 2009;103(6):800–12.

    Article  PubMed  Google Scholar 

  96. Creticos PS. Advances in synthetic peptide immuno-regulatory epitopes. World Allergy Organ J. 2014;7(1):1–6.

    Google Scholar 

  97. Lin J, Bruni FM, Fu Z, Maloney J, Bardina L, Boner AL, et al. A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay. J Allergy Clin Immunol. 2012;129(5):1321–8.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. DeLong JH, Simpson KH, Wambre E, James EA, Robinson D, Kwok WW. Ara h 1–reactive T cells in individuals with peanut allergy. J Allergy Clin Immunol. 2011;127(5):1211–8.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Constant SL, Bottomly K. Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol. 1997;15(1):297–322.

    Article  CAS  PubMed  Google Scholar 

  100. Bluestone JA. New perspectives of C1328-137-mediated T cell costimulation. Immunity. 1995;2(6):555–9.

    Article  CAS  PubMed  Google Scholar 

  101. Workman CJ, Szymczak-Workman AL, Collison LW, Pillai MR, Vignali DA. The development and function of regulatory T cells. Cell Mol Life Sci. 2009;66(16):2603–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Carballido J, Carballido-Perrig N, Oberli-Schrämmli A, Heusser CH, Blaser K. Regulation of IgE and IgG4 responses by allergen specific T-cell clones to bee venom phospholipase A2 in vitro. J Allergy Clin Immunol. 1994;93(4):758–67.

    Article  CAS  PubMed  Google Scholar 

  103. Norman PS, Ohman JL Jr, Long A, Creticos PS, Gefter MA, Shaked ZE, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med. 1996;154(6):1623–8.

    Article  CAS  PubMed  Google Scholar 

  104. James JM, Burks AW, Eigenmann P. Food allergy. London: Elsevier Health Sciences; 2011.

    Google Scholar 

  105. Jahn-Schmid B, Radakovics A, Lüttkopf D, Scheurer S, Vieths S, Ebner C, et al. Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1–related food allergens. J Allergy Clin Immunol. 2005;116(1):213–9.

    Article  CAS  PubMed  Google Scholar 

  106. Soyer O, Akdis M, Ring J, Behrendt H, Crameri R, Lauener R, et al. Mechanisms of peripheral tolerance to allergens. Allergy. 2013;68(2):161–70.

    Article  CAS  PubMed  Google Scholar 

  107. Belkaid Y, Oldenhove G. Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity. 2008;29(3):362–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Aalberse R, Crameri R. IgE-binding epitopes: a reappraisal. Allergy. 2011;66(10):1261–74.

    Article  CAS  PubMed  Google Scholar 

  109. Müller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F, 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.

    Article  PubMed  Google Scholar 

  110. 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.e7.

    Article  CAS  PubMed  Google Scholar 

  111. Oldfield WL, Larche M, Kay A. 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. The Lancet. 2002;360(9326):47–53.

    Article  CAS  Google Scholar 

  112. 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 

  113. Rupa P, Mine Y. Oral immunotherapy with immunodominant T-cell epitope peptides alleviates allergic reactions in a Balb/c mouse model of egg allergy. Allergy. 2012;67(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  114. Hirahara K, Hisatsune T, Choi C-Y, Kaminogawa S. Profound immunological tolerance in the antibody response against bovine αs1-casein induced by intradermal administration of a dominant T cell determinant. Clin Immunol Immunopathol. 1995;76(1):12–8.

    Article  CAS  PubMed  Google Scholar 

  115. Knipping K, Van Esch BC, Van Ieperen-van Dijk AG, Van Hoffen E, Van Baalen T, Knippels LM, et al. Enzymatic treatment of whey proteins in cow’s milk results in differential inhibition of IgE-mediated mast cell activation compared to T-cell activation. Int Arch Allergy Immunol. 2012;159(3):263–70.

    Article  CAS  PubMed  Google Scholar 

  116. Pecquet S, Bovetto L, Maynard F, Fritsché R. Peptides obtained by tryptic hydrolysis of bovine β-lactoglobulin induce specific oral tolerance in mice. J Allergy Clin Immunol. 2000;105(3):514–21.

    Article  CAS  PubMed  Google Scholar 

  117. Meulenbroek LA, Esch BC, Hofman GA, Hartog Jager CF, Nauta AJ, Willemsen LE, et al. Oral treatment with β-lactoglobulin peptides prevents clinical symptoms in a mouse model for cow’s milk allergy. Pediatr Allergy Immunol. 2013;24(7):656–64.

    Article  PubMed  Google Scholar 

  118. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127(3):654–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, de Oliveira LCL, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126(1):83–91.e1.

    Article  CAS  PubMed  Google Scholar 

  120. Moran TP, Burks AW. Is clinical tolerance possible after allergen immunotherapy? Curr Allergy Asthma Rep. 2015;15(5):1–7.

    Article  CAS  Google Scholar 

  121. Glaspole I, De Leon M, Rolland J, O’hehir R. Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2. Allergy. 2005;60(1):35–40.

    Article  CAS  PubMed  Google Scholar 

  122. 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.

    Article  CAS  PubMed  Google Scholar 

  123. Prickett S, Voskamp A, Phan T, Dacumos-Hill A, Mannering S, Rolland J, et al. Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic. Clin Exp Allergy. 2013;43(6):684–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Romagnani S. The role of lymphocytes in allergic disease. J Allergy Clin Immunol. 2000;105(3):399–408.

    Article  CAS  PubMed  Google Scholar 

  125. Byrne A, Malka-Rais J, Burks A, Fleischer D. How do we know when peanut and tree nut allergy have resolved, and how do we keep it resolved? Clin Exp Allergy. 2010;40(9):1303–11.

    Article  CAS  PubMed  Google Scholar 

  126. Larché M. Mechanisms of peptide immunotherapy in allergic airways disease. Ann Am Thorac Soc. 2014;11(Supplement 5):S292–S6.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Faria A, Weiner HL. Oral tolerance. Immunol Rev. 2005;206(1):232–59.

    Article  CAS  PubMed  Google Scholar 

  128. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124(2):292–300.e97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Bluestone JA, Tang Q. Immunotherapy: making the case for precision medicine. Sci Transl Med. 2015;7(280):280ed3.

    Article  PubMed  Google Scholar 

  131. Flicker S, Valenta R. Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol. 2003;132(1):13–24.

    Article  CAS  PubMed  Google Scholar 

  132. Buyuktiryaki B, Cavkaytar O, Sahiner UM, Yilmaz EA, Yavuz ST, Soyer O, et al. Cor a 14, hazelnut-specific IgE, and SPT as a reliable tool in hazelnut allergy diagnosis in Eastern Mediterranean children. J Allergy Clin Immunol Pract. 2016;4(2):265–72.e3.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  134. Bohle B. Allergen-specific T lymphocytes as targets for specific immunotherapy: Striking at the roots of type I allergy. Arch Immunol Ther Exp (Warsz). 2002;50(4):233–42.

    Google Scholar 

  135. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11(12):852–63.

    Article  CAS  PubMed  Google Scholar 

  136. O’Hehir RE, Yssel H, Verma S, de Vries JE, Spits H, Lamb JR. Clonal analysis of differential lymphokine production in peptide and superantigen induced T cell anergy. Int Immunol. 1991;3(8):819–26.

    Article  PubMed  Google Scholar 

  137. Worm M, Lee H-H, 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):89–97.e14.

    Article  CAS  PubMed  Google Scholar 

  138. O'hehir R, Aguilar B, Schmidt T, Gollnick S, Lamb J. Functional inactivation of Dermatophagoides spp.(house dust mite) reactive human T-cell clones. Clin Exp Allergy. 1991;21(2):209–15.

    Article  CAS  PubMed  Google Scholar 

  139. Coombes JL, Siddiqui KR, Arancibia-Cárcamo CV, Hall J, Sun C-M, Belkaid Y, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β–and retinoic acid–dependent mechanism. J Exp Med. 2007;204(8):1757–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Josefowicz SZ, Lu L-F, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Syed A, Garcia MA, Lyu S-C, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133(2):500–10.e11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Steinbrink K, Wölfl M, Jonuleit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 1997;159(10):4772–80.

    CAS  PubMed  Google Scholar 

  143. Bellinghausen I, Knop J, Saloga J. The role of interleukin 10 in the regulation of allergic immune responses. Int Arch Allergy Immunol. 2001;126(2):97–101.

    Article  CAS  PubMed  Google Scholar 

  144. Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, et al. Antigen-specific regulatory T cells develop via the ICOS–ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med. 2002;8(9):1024–32.

    Article  CAS  PubMed  Google Scholar 

  145. Farrugia M, Baron B. Role of regulatory T-cells in oral tolerance and immunotherapy. Biochem Physiol. 2016;5(199):2.

    Google Scholar 

  146. Murray JS. How the MHC selects Th1/Th2 immunity. Immunol Today. 1998;19(4):157–62.

    Article  CAS  PubMed  Google Scholar 

  147. Bannon GA, Cockrell G, Connaughton C, West CM, Helm R, Stanley JS, et al. Engineering, characterization and in vitro efficacy of the major peanut allergens for use in immunotherapy. Int Arch Allergy Immunol. 2001;124(1–3):70–2.

    Article  CAS  PubMed  Google Scholar 

  148. Larché M. T cell epitope-based allergy vaccines. In: Vaccines against allergies. Berlin: Springer; 2011. p. 107–19.

    Chapter  Google Scholar 

  149. Simms E, Rudulier C, Wattie J, Kwok WW, James EA, Moldaver DM, et al. Ara h 1 peptide immunotherapy ameliorates peanut-induced anaphylaxis. J Allergy Clin Immunol. 2015;135(2):AB158.

    Article  Google Scholar 

  150. Simms E, Wattie J, Waserman S, Jordana M, Larché M. Ara h 1 peptide immunotherapy protects against peanut-induced anaphylaxis in a dose-dependent manner. J Allergy Clin Immunol. 2016;137(2):AB410.

    Article  Google Scholar 

  151. Sicherer SH, Sampson HA. Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol. 2007;120(3):491–503.

    Article  PubMed  Google Scholar 

  152. Bohle B, Schwihla H, Hu H-Z, Friedl-Hajek R, Sowka S, Ferreira F, et al. Long-lived Th2 clones specific for seasonal and perennial allergens can be detected in blood and skin by their TCR-hypervariable regions. J Immunol. 1998;160(4):2022–7.

    CAS  PubMed  Google Scholar 

  153. Baranyi U, Gattringer M, Valenta R, Wekerle T. Cell-based therapy in allergy. In: Vaccines against allergies. Berlin: Springer; 2011. p. 161–79.

    Chapter  Google Scholar 

  154. Pons L, Palmer K, Burks W. Towards immunotherapy for peanut allergy. Curr Opin Allergy Clin Immunol. 2005;5(6):558–62.

    CAS  PubMed  Google Scholar 

  155. Shreffler WG, Beyer K, Chu T-HT, Burks AW, Sampson HA. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol. 2004;113(4):776–82.

    Article  CAS  PubMed  Google Scholar 

  156. Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Hoyne GF, O’hehir R, Wraith D, Thomas W, Lamb J. Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice. J Exp Med. 1993;178(5):1783–8.

    Article  CAS  PubMed  Google Scholar 

  158. O’Hehir R, Hoyne G, Thomas W, Lamb J. House dust mite allergy: from T-cell epitopes to immuno-therapy. Eur J Clin Invest. 1993;23(12):763–72.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands

    Iris Pelgrim & Huub F. J. Savelkoul

  2. Allergy Consortium, Wageningen University, Wageningen, The Netherlands

    Huub F. J. Savelkoul

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  1. Iris Pelgrim
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  1. Department Cellular and Molecular Nutrition, Tehran University of Medical Sciences and Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Maryam Mahmoudi

  2. Research Center for Immunodeficiencies, Tehran University of Medical Sciences and Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Nima Rezaei

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Pelgrim, I., Savelkoul, H.F.J. (2019). Potency of T-Cell Epitope-Based Peptide Vaccines in Food Allergy Treatment. In: Mahmoudi, M., Rezaei, N. (eds) Nutrition and Immunity. Springer, Cham. https://doi.org/10.1007/978-3-030-16073-9_17

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