Seminars in Immunopathology

, Volume 34, Issue 5, pp 703–714 | Cite as

The future of food allergy therapeutics



Food allergy is increasing in prevalence in westernized countries, leading to significant morbidity including nutritional deficiencies and growth delay as well as psychosocial burdens and the potential for fatal anaphylaxis. There is currently no effective form of therapy, and the mainstay of treatment remains strict avoidance. However, there are a number of promising therapeutic strategies currently being investigated for the treatment of food allergies. Allergen-specific approaches, such as various forms of immunotherapy, have been a major focus of investigation and appear to be promising methods of desensitization. More recently, the addition of anti-IgE monoclonal antibodies (mAbs) to immunotherapy regimens has been studied. Early work with antigen-fixed leukocytes in a murine model has shown promise in inducing tolerance, as have vaccines containing modified recombinant food proteins coadministered with heat-killed Escherichia coli. Nonspecific approaches include a Chinese herbal formulation, anti-IgE mAbs, and Trichuris suis ova therapy. The array of treatment modalities currently being investigated increases the likelihood of finding one or more effective therapies for the treatment of food allergy.


Food allergy Oral immunotherapy (OIT) Double-blind Placebo-controlled food challenge (DBPCFC) Anti-IgE antibody/omalizumab Desensitization 


  1. 1.
    Branum AM, Lukacs SL (2009) Food allergy among children in the United States. Pediatrics 124(6):1549–1555PubMedCrossRefGoogle Scholar
  2. 2.
    Rona RJ et al (2007) The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 120(3):638–646PubMedCrossRefGoogle Scholar
  3. 3.
    Branum AM, Lukacs SL (2008) Food allergy among U.S. children: trends in prevalence and hospitalizations. NCHS Data Brief. (10):1–8Google Scholar
  4. 4.
    Sicherer SH et al (2010) US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol 125(6):1322–1326PubMedCrossRefGoogle Scholar
  5. 5.
    Sicherer SH, Sampson HA (2007) Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 120(3):491–503, quiz 504-5PubMedCrossRefGoogle Scholar
  6. 6.
    Decker WW et al (2008) The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol 122(6):1161–1165PubMedCrossRefGoogle Scholar
  7. 7.
    Gupta R et al (2007) Time trends in allergic disorders in the UK. Thorax 62(1):91–96PubMedCrossRefGoogle Scholar
  8. 8.
    Bock SA, Munoz-Furlong A, Sampson HA (2007) Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 119(4):1016–1018PubMedCrossRefGoogle Scholar
  9. 9.
    Christie L et al (2002) Food allergies in children affect nutrient intake and growth. J Am Diet Assoc 102(11):1648–1651PubMedCrossRefGoogle Scholar
  10. 10.
    Mennella JA, Ventura AK, Beauchamp GK (2011) Differential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas. Pediatrics 127(1):110–118PubMedCrossRefGoogle Scholar
  11. 11.
    Lieberman JA, Sicherer SH (2011) Quality of life in food allergy. Curr Opin Allergy Clin Immunol 11(3):236–242PubMedCrossRefGoogle Scholar
  12. 12.
    Flokstra-de Blok BM et al (2010) Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires. Allergy 65(8):1031–1038PubMedCrossRefGoogle Scholar
  13. 13.
    Lieberman JA et al (2010) Bullying among pediatric patients with food allergy. Ann Allergy Asthma Immunol 105(4):282–286PubMedCrossRefGoogle Scholar
  14. 14.
    Boyce JA et al (2010) Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 126(6 Suppl):S1–S58PubMedGoogle Scholar
  15. 15.
    Burks AW et al (2011) NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics 128(5):955–965PubMedCrossRefGoogle Scholar
  16. 16.
    Nowak-Wegrzyn A, Sampson HA (2011) Future therapies for food allergies. J Allergy Clin Immunol 127(3):558–573, quiz 574-5PubMedCrossRefGoogle Scholar
  17. 17.
    Burks AW, Laubach S, Jones SM (2008) Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol 121(6):1344–1350PubMedCrossRefGoogle Scholar
  18. 18.
    Chehade M, Mayer L (2005) Oral tolerance and its relation to food hypersensitivities. J Allergy Clin Immunol 115(1):3–12, quiz 13PubMedCrossRefGoogle Scholar
  19. 19.
    Sicherer SH, Sampson HA (2010) Food allergy. J Allergy Clin Immunol 125(2 Suppl 2):S116–S125PubMedCrossRefGoogle Scholar
  20. 20.
    Untersmayr E, Jensen-Jarolim E (2008) The role of protein digestibility and antacids on food allergy outcomes. J Allergy Clin Immunol 121(6):1301–1308, quiz 1309-10PubMedCrossRefGoogle Scholar
  21. 21.
    Pali-Scholl I et al (2008) Anti-acids lead to immunological and morphological changes in the intestine of BALB/c mice similar to human food allergy. Exp Toxicol Pathol 60(4–5):337–345PubMedCrossRefGoogle Scholar
  22. 22.
    Groschwitz KR, Hogan SP (2009) Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 124(1):3–20, quiz 21-2PubMedCrossRefGoogle Scholar
  23. 23.
    Manicassamy S et al (2010) Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329(5993):849–853PubMedCrossRefGoogle Scholar
  24. 24.
    Navuluri L et al (2006) Allergic and anaphylactic response to sesame seeds in mice: identification of Ses i 3 and basic subunit of 11 s globulins as allergens. Int Arch Allergy Immunol 140(3):270–276PubMedCrossRefGoogle Scholar
  25. 25.
    Fox AT et al (2009) Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol 123(2):417–423PubMedCrossRefGoogle Scholar
  26. 26.
    Lack G (2012) Update on risk factors for food allergy. J Allergy Clin Immunol, Google Scholar
  27. 27.
    Brown SJ et al (2011) Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 127(3):661–667PubMedCrossRefGoogle Scholar
  28. 28.
    Vickery BP et al (2011) Mechanisms of immune tolerance relevant to food allergy. J Allergy Clin Immunol 127(3):576–584, quiz 585-6PubMedCrossRefGoogle Scholar
  29. 29.
    Eifan AO, Shamji MH, Durham SR (2011) Long-term clinical and immunological effects of allergen immunotherapy. Curr Opin Allergy Clin Immunol 11(6):586–593PubMedCrossRefGoogle Scholar
  30. 30.
    Patriarca G et al (2003) Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 17(3):459–465PubMedCrossRefGoogle Scholar
  31. 31.
    Varshney P et al (2011) A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol 127(3):654–660PubMedCrossRefGoogle Scholar
  32. 32.
    Jones SM et al (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124(2):292–300, 300 e1-97PubMedCrossRefGoogle Scholar
  33. 33.
    Kim EH et al (2011) Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol 127(3):640–646 e1PubMedCrossRefGoogle Scholar
  34. 34.
    Freeman J (1930) “Rush” inoculation. Lancet 1:744CrossRefGoogle Scholar
  35. 35.
    Hunt KJ et al (1978) A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med 299(4):157–161PubMedCrossRefGoogle Scholar
  36. 36.
    Oppenheimer JJ et al (1992) Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol 90(2):256–262PubMedCrossRefGoogle Scholar
  37. 37.
    Nelson HS et al (1997) Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol 99(6 Pt 1):744–751PubMedCrossRefGoogle Scholar
  38. 38.
    Land MH, Kim EH, Burks AW (2011) Oral desensitization for food hypersensitivity. Immunol Allergy Clin North Am 31(2):367–376, xiPubMedCrossRefGoogle Scholar
  39. 39.
    Scurlock AM et al (2010) Pediatric food allergy and mucosal tolerance. Mucosal Immunol 3(4):345–354PubMedCrossRefGoogle Scholar
  40. 40.
    Schofield AT (1908) A case of egg poisoning. Lancet 1:716CrossRefGoogle Scholar
  41. 41.
    Patriarca C et al (1984) Oral specific hyposensitization in the management of patients allergic to food. Allergol Immunopathol (Madr) 12(4):275–281Google Scholar
  42. 42.
    Bauer A et al (1999) Oral rush desensitization to milk. Allergy 54(8):894–895PubMedCrossRefGoogle Scholar
  43. 43.
    Buchanan AD et al (2007) Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 119(1):199–205PubMedCrossRefGoogle Scholar
  44. 44.
    Staden U et al (2007) Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 62(11):1261–1269PubMedCrossRefGoogle Scholar
  45. 45.
    Longo G et al (2008) Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. J Allergy Clin Immunol 121(2):343–347PubMedCrossRefGoogle Scholar
  46. 46.
    Skripak JM et al (2008) A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol 122(6):1154–1160PubMedCrossRefGoogle Scholar
  47. 47.
    Wood RA (2003) The natural history of food allergy. Pediatrics 111(6 Pt 3):1631–1637PubMedGoogle Scholar
  48. 48.
    Fleischer DM (2007) The natural history of peanut and tree nut allergy. Curr Allergy Asthma Rep 7(3):175–181PubMedCrossRefGoogle Scholar
  49. 49.
    Clark AT et al (2009) Successful oral tolerance induction in severe peanut allergy. Allergy 64(8):1218–1220PubMedCrossRefGoogle Scholar
  50. 50.
    Nadeau KC et al (2012) Oral immunotherapy and anti-IgE antibody-adjunctive treatment for food allergy. Immunol Allergy Clin North Am 32(1):111–133PubMedCrossRefGoogle Scholar
  51. 51.
    Blumchen K et al (2010) Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 126(1):83–91 e1PubMedCrossRefGoogle Scholar
  52. 52.
    Fisher HR, Toit GD, Lack G (2011) Specific oral tolerance induction in food allergic children: is oral desensitisation more effective than allergen avoidance? Arch Dis Child 96(3):259–264PubMedCrossRefGoogle Scholar
  53. 53.
    Thyagarajan A et al (2010) Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol 126(1):31–32PubMedCrossRefGoogle Scholar
  54. 54.
    Durham SR et al (2012) SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 129(3):717–725 e5PubMedCrossRefGoogle Scholar
  55. 55.
    Mempel M et al (2003) Severe anaphylaxis to kiwi fruit: immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol 111(6):1406–1409PubMedCrossRefGoogle Scholar
  56. 56.
    Enrique E et al (2005) Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol 116(5):1073–1079PubMedCrossRefGoogle Scholar
  57. 57.
    Fernandez-Rivas M et al (2009) Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy 64(6):876–883PubMedCrossRefGoogle Scholar
  58. 58.
    Keet CA et al (2012) The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 129(2):448–455.e5PubMedCrossRefGoogle Scholar
  59. 59.
    Otsu K, Fleischer DM (2012) Therapeutics in food allergy: the current state of the art. Curr Allergy Asthma Rep 12(1):48–54PubMedCrossRefGoogle Scholar
  60. 60.
    Dupont C et al (2010) Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol 125(5):1165–1167PubMedCrossRefGoogle Scholar
  61. 61.
    Mondoulet L et al (2010) Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy 40(4):659–667PubMedCrossRefGoogle Scholar
  62. 62.
    Mondoulet L et al (2011) Epicutaneous immunotherapy using a new epicutaneous delivery system in mice sensitized to peanuts. Int Arch Allergy Immunol 154(4):299–309PubMedCrossRefGoogle Scholar
  63. 63.
    MacGlashan DW Jr et al (1997) Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 158(3):1438–1445PubMedGoogle Scholar
  64. 64.
    Pelaia G et al (2008) Omalizumab in the treatment of severe asthma: efficacy and current problems. Ther Adv Respir Dis 2(6):409–421PubMedCrossRefGoogle Scholar
  65. 65.
    Leung DY et al (2003) Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 348(11):986–993PubMedCrossRefGoogle Scholar
  66. 66.
    Kuehr J et al (2002) Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol 109(2):274–280PubMedCrossRefGoogle Scholar
  67. 67.
    Casale TB et al (2006) Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 117(1):134–140PubMedCrossRefGoogle Scholar
  68. 68.
    Nadeau KC et al (2011) Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol 127(6):1622–1624PubMedCrossRefGoogle Scholar
  69. 69.
    Hofmann AM et al (2009) Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol 124(2):286–291, 291 e1-6PubMedCrossRefGoogle Scholar
  70. 70.
    Meglio P et al (2004) A protocol for oral desensitization in children with IgE-mediated cow’s milk allergy. Allergy 59(9):980–987PubMedCrossRefGoogle Scholar
  71. 71.
    Smarr CB et al (2011) Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy. J Immunol 187(10):5090–5098PubMedCrossRefGoogle Scholar
  72. 72.
    Miller SD, Wetzig RP, Claman HN (1979) The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells. J Exp Med 149(3):758–773PubMedCrossRefGoogle Scholar
  73. 73.
    Luo X et al (2008) ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms. Proc Natl Acad Sci U S A 105(38):14527–14532PubMedCrossRefGoogle Scholar
  74. 74.
    Li XM et al (2003) Persistent protective effect of heat-killed Escherichia coli producing “engineered”, recombinant peanut proteins in a murine model of peanut allergy. J Allergy Clin Immunol 112(1):159–167PubMedCrossRefGoogle Scholar
  75. 75.
    Li XM et al (2003) Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model. J Immunol 170(6):3289–3295PubMedGoogle Scholar
  76. 76.
    Chan CK et al (2006) Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial. Pediatr Allergy Immunol 17(5):316–322PubMedCrossRefGoogle Scholar
  77. 77.
    Chang TT, Huang CC, Hsu CH (2006) Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma. Phytother Res 20(5):342–347PubMedCrossRefGoogle Scholar
  78. 78.
    Hsu CH, Lu CM, Chang TT (2005) Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma. Pediatr Allergy Immunol 16(1):76–81PubMedCrossRefGoogle Scholar
  79. 79.
    Kao ST et al (2000) The effect of Chinese herbal medicine, xiao-qing-long tang (XQLT), on allergen-induced bronchial inflammation in mite-sensitized mice. Allergy 55(12):1127–1133PubMedCrossRefGoogle Scholar
  80. 80.
    Li XM, Brown L (2009) Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy. J Allergy Clin Immunol 123(2):297–306, quiz 307-8PubMedCrossRefGoogle Scholar
  81. 81.
    Bensky DBR (1990) Chinese herbal medicine: formulas & strategies. Eastland: Seattle.Google Scholar
  82. 82.
    Qu C et al (2007) Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-regulation of interferon-gamma. Clin Exp Allergy 37(6):846–855PubMedCrossRefGoogle Scholar
  83. 83.
    Srivastava KD et al (2005) The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy. J Allergy Clin Immunol 115(1):171–178PubMedCrossRefGoogle Scholar
  84. 84.
    Srivastava KD et al (2009) Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gamma-producing CD8+ T cells. J Allergy Clin Immunol 123(2):443–451PubMedCrossRefGoogle Scholar
  85. 85.
    Patil SP et al (2011) Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: extended phase I study. J Allergy Clin Immunol 128(6):1259–1265 e2PubMedCrossRefGoogle Scholar
  86. 86.
    Song Y et al (2010) Food allergy herbal formula 2 protection against peanut anaphylactic reaction is via inhibition of mast cells and basophils. J Allergy Clin Immunol 126(6):1208–1217 e3PubMedCrossRefGoogle Scholar
  87. 87.
    Wang J et al (2010) Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study. Ann Allergy Asthma Immunol 105(1):75–84PubMedCrossRefGoogle Scholar
  88. 88.
    Sampson HA et al (2011) A phase II, randomized, double-blind, parallel-group, placebo-controlled oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol 127(5):1309–1310 e1PubMedCrossRefGoogle Scholar
  89. 89.
    Medeiros M Jr et al (2003) Schistosoma mansoni infection is associated with a reduced course of asthma. J Allergy Clin Immunol 111(5):947–951PubMedCrossRefGoogle Scholar
  90. 90.
    Bashir ME et al (2002) An enteric helminth infection protects against an allergic response to dietary antigen. J Immunol 169(6):3284–3292PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.Department of PediatricsUniversity of North Carolina Medical CenterChapel HillUSA

Personalised recommendations