Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 2, pp 162–171 | Cite as

Peptide and Recombinant Allergen Vaccines for Food Allergy

  • Quindelyn S. Cook
  • A. Wesley Burks
Article

Abstract

Food allergy is a significant public health problem, with no suitable treatments available for patients. Currently, patients are limited to avoidance and the use of readily available emergency medications. Immunotherapy is an appealing therapeutic strategy for inducing tolerance. Studies with whole native allergens have demonstrated the efficacy of immunotherapy for food allergy; however, the risk of IgE-mediated reactions with such treatment is significant. Advances in molecular biology techniques, including purification, sequencing, and cloning, have allowed researchers to identify specific allergen components and T cell binding epitopes. Support for the use of recombinant and peptide vaccines for food allergy comes from prior studies involving aeroallergens and hymenoptera venom. By manipulating allergen structure and IgE binding, allergenicity can be reduced, thereby reducing systemic reactions, making recombinant and peptide vaccines a safe and effective form of immunotherapy. Pre-clinical studies using in vitro and murine models demonstrated a more tolerant state following the use of these therapies. Studies with human subjects will be necessary to characterize the effects of recombinant and peptide food allergy vaccines and to demonstrate a safe treatment option for patients.

Keywords

Food allergy Vaccines Immunotherapy Peptide immunotherapy Recombinant food allergens 

Notes

Compliance with Ethical Standards

Conflict of Interest

Quindelyn Cook, MD is an Allergy Immunology fellow at the University of North Carolina. Dr. Cook declares no other conflict of interest.

A. Wesley Burks, MD has received research grants from Food Allergy Research and Education (FARE), National Institutes of Health, and Wallace Research Foundation. Dr. Burks is a consultant on the advisory board for the following: Aimmune (Advisory Panel); Astellas Biomerica, Inc.; Evelo/Epiva Biosciences; GLG Research; Insys Therapeutics; PPD Development; Sanofi US Svcs, UKKO; and Valeant Pharma North America/consultant. Dr. Burks reports ownership interest in Allertein (minority stockholder).

Ethical Approval

This is a review article. No studies with human participants or animals were performed by any of the authors.

Informed Consent

This is a review article. For this type of study, formal consent is not required.

References

  1. 1.
    Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K, Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon RA, Vickery BP, Wood R, Sampson HA, Randolph C, Bernstein D, Blessing-Moore J, Khan D, Lang D, Nicklas R, Oppenheimer J, Portnoy J, Randolph C, Schuller D, Spector S, Tilles SA, Wallace D, Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K, Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon RA, Vickery BP, Wood R (2014) Food allergy: a practice parameter update—2014. J Allergy Clin Immunol 134(5):1016–1025.e1043.  https://doi.org/10.1016/j.jaci.2014.05.013 CrossRefPubMedGoogle Scholar
  2. 2.
    Sicherer SH (2011) Epidemiology of food allergy. J Allergy Clin Immunol 127(3):594–602.  https://doi.org/10.1016/j.jaci.2010.11.044 CrossRefPubMedGoogle Scholar
  3. 3.
    Sicherer SH, Munoz-Furlong A, Godbold JH, Sampson HA (2010) US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol 125(6):1322–1326.  https://doi.org/10.1016/j.jaci.2010.03.029 CrossRefPubMedGoogle Scholar
  4. 4.
    Gernez Y, Nowak-Wegrzyn A (2017) Immunotherapy for food allergy: are we there yet? J Allergy Clin Immunol Pract 5(2):250–272. Comprehensive and up-to-date review of clinical SLIT, OIT, and EPIT trials for food allergy.  https://doi.org/10.1016/j.jaip.2016.12.004 CrossRefPubMedGoogle Scholar
  5. 5.
    Lieberman JA, Nowak-Wegrzyn A (2012) Vaccines and immunomodulatory therapies for food allergy. Curr Allergy Asthma Rep 12(1):55–63.  https://doi.org/10.1007/s11882-011-0232-5 CrossRefPubMedGoogle Scholar
  6. 6.
    Ali RF, Larche M (2005) Peptide-based immunotherapy: a novel strategy for allergic disease. Expert Rev Vaccines 4(6):881–889.  https://doi.org/10.1586/14760584.4.6.881 CrossRefPubMedGoogle Scholar
  7. 7.
    Kostadinova AI, Willemsen LE, Knippels LM, Garssen J (2013) Immunotherapy—risk/benefit in food allergy. Pediatr Allergy Immunol 24(7):633–644.  https://doi.org/10.1111/pai.12122 CrossRefPubMedGoogle Scholar
  8. 8.
    Prickett SR, Rolland JM, O'Hehir RE (2015) Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy. Clin Exp Allergy 45(6):1015–1026.  https://doi.org/10.1111/cea.12554 CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Gupta K, Kumar S, Das M, Dwivedi PD (2014) Peptide based immunotherapy: a pivotal tool for allergy treatment. Int Immunopharmacol 19(2):391–398.  https://doi.org/10.1016/j.intimp.2014.01.030 CrossRefPubMedGoogle Scholar
  10. 10.
    Alexander C, Tarzi M, Larche M, Kay AB (2005) The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy 60(10):1269–1274.  https://doi.org/10.1111/j.1398-9995.2005.00885.x CrossRefPubMedGoogle Scholar
  11. 11.
    Oldfield WLG, Larché M, Kay AB (2002) Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360(9326):47–53.  https://doi.org/10.1016/S0140-6736(02)09332-7 CrossRefPubMedGoogle Scholar
  12. 12.
    Virtanen T (2006) Prospects for peptide-based immunotherapy for dog allergy. Curr Opin Allergy Clin Immunol 6:461–465CrossRefPubMedGoogle Scholar
  13. 13.
    Muller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F, Blaser K (1998) 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 101(6):747–754.  https://doi.org/10.1016/S0091-6749(98)70402-6 CrossRefPubMedGoogle Scholar
  14. 14.
    Carballido JM, Carballido-Perrig N, Kagi MK, Meloen RH, Wuthrich B, Heusser CH, Blaser K (1993) T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2. J Immunol 150:3582–3591PubMedGoogle Scholar
  15. 15.
    Yang M, Mine Y (2009) Novel T-cell epitopes of ovalbumin in BALB/c mouse: potential for peptide-immunotherapy. Biochem Biophys Res Commun 378(2):203–208.  https://doi.org/10.1016/j.bbrc.2008.11.037 CrossRefPubMedGoogle Scholar
  16. 16.
    Yang M, Yang C, Mine Y (2010) Multiple T cell epitope peptides suppress allergic responses in an egg allergy mouse model by the elicitation of forkhead box transcription factor 3- and transforming growth factor-beta-associated mechanisms. Clin Exp Allergy 40(4):668–678.  https://doi.org/10.1111/j.1365-2222.2009.03442.x CrossRefPubMedGoogle Scholar
  17. 17.
    Prickett SR, Voskamp AL, Dacumos-Hill A, Symons K, Rolland JM, O'Hehir RE (2011) Ara h 2 peptides containing dominant CD4+ T-cell epitopes: candidates for a peanut allergy therapeutic. J Allergy Clin Immunol 127(3):608–615 e601-605.  https://doi.org/10.1016/j.jaci.2010.09.027 CrossRefPubMedGoogle Scholar
  18. 18.
    Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY (1992) Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol 90(2):256–262.  https://doi.org/10.1016/0091-6749(92)90080-L CrossRefPubMedGoogle Scholar
  19. 19.
    Nelson HS, Lahr J, Rule R, Bock A, Leung D (1997) Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol 99(6):744–751.  https://doi.org/10.1016/S0091-6749(97)80006-1 CrossRefPubMedGoogle Scholar
  20. 20.
    Bock SA, Munoz-Furlong A, Sampson HA (2007) Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 119(4):1016–1018.  https://doi.org/10.1016/j.jaci.2006.12.622 CrossRefPubMedGoogle Scholar
  21. 21.
    Glaspole IN, de Leon MP, Rolland JM, O'Hehir RE (2005) Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2. Allergy 60(1):35–40.  https://doi.org/10.1111/j.1398-9995.2004.00608.x CrossRefPubMedGoogle Scholar
  22. 22.
    Prickett SR, Voskamp AL, Phan T, Dacumos-Hill A, Mannering SI, Rolland JM, O'Hehir RE (2013) Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic. Clin Exp Allergy 43(6):684–697.  https://doi.org/10.1111/cea.12113 CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Ramesh M, Yuenyongviwat A, Konstantinou GN, Lieberman J, Pascal M, Masilamani M, Sampson HA (2016) Peanut T-cell epitope discovery: Ara h 1. J Allergy Clin Immunol 137(6):1764–1771.e1764.  https://doi.org/10.1016/j.jaci.2015.12.1327 CrossRefPubMedGoogle Scholar
  24. 24.
    Pascal M, Konstantinou GN, Masilamani M, Lieberman J, Sampson HA (2013) In silico prediction of Ara h 2 T cell epitopes in peanut allergic children. Clin Exp Allergy 43(1):116–127.  https://doi.org/10.1111/cea.12014 CrossRefPubMedGoogle Scholar
  25. 25.
    DeLong JH, Simpson KH, Wambre E, James EA, Robinson D, Kwok WW (2011) Ara h 1-reactive T cells in individuals with peanut allergy. J Allergy Clin Immunol 127(5):1211–1218.e1213.  https://doi.org/10.1016/j.jaci.2011.02.028 CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Li S, Li XM, Burks AW, Sampson HA (2001) Modulation of peanut allergy by peptide-based immunotherapy. J Allergy Clin Immunol 107(suppl):S233Google Scholar
  27. 27.
    Simms E, Wattie J, Waserman S, Jordana M, Larche M (2016) Ara h1 peptide immunotherapy protects against peanut-induced anaphylaxis in a dose-dependent manner. J Allergy Clin Immunol 137(2):AB410.  https://doi.org/10.1016/j.jaci.2015.12.1271 CrossRefGoogle Scholar
  28. 28.
    Simms E, Rudulier C, Wattie J, Kwok WW, James EA, Moldaver DM, Jordana M, Larche M (2015) Ara h 1 peptide immunotherpay ameliorates peanut-induced anaphylaxis. J Allergy Clin Immunol 135(2):AB158.  https://doi.org/10.1016/j.jaci.2014.12.1456 CrossRefGoogle Scholar
  29. 29.
    Wood RA, Sicherer SH, Burks AW, Grishin A, Henning AK, Lindblad R, Stablein D, Sampson HA (2013) 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 68(6):803–808.  https://doi.org/10.1111/all.12158 CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Hochwallner H, Schulmeister U, Swoboda I, Spitzauer S, Valenta R (2014) Cow’s milk allergy: from allergens to new forms of diagnosis, therapy, and prevention. Methods 66(1):22–33.  https://doi.org/10.1016/j.ymeth.2013.08.005 CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Fiocchi A, Brozek J, Schunemann H, Bahna SL, von Berg A, Beyer K et al (2010) World allergy organization (WAO) diagnosis and rationale for action against cow’s milk allergy (DRACMA) guidelines. World Allergy Organ J 3(4):57–61.  https://doi.org/10.1097/WOX.0b013e3181defeb9 CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Kondo M, Kaneko H, Fukao T, Suzuki K, Sakaguchi H, Shinoda S, Kato Z, Matsui E, Teramoto T, Nakano T, Kondo N (2008) The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitution of T-cell core epitope. Pediatr Allergy Immunol 19(7):592–598.  https://doi.org/10.1111/j.1399-3038.2007.00704.x CrossRefPubMedGoogle Scholar
  33. 33.
    Jarvinen KM, Chatchatee P, Bardina L, Beyer K, Sampson HA (2001) IgE and IgG binding epitopes on a-lactalbumin and B-lactoglobulin in cow’s milk allergy. Int Arch Allergy Immunol 126(2):111–118.  https://doi.org/10.1159/000049501 CrossRefPubMedGoogle Scholar
  34. 34.
    Ruiter B, Tregoat V, M'rabet L, Garssen J, Bruijnzeel-Koomen CA, Knol EF, Hoffen E (2006) Characterization of T cell epitopes in alphas1-casein in cow’s milk allergic, atopic and non-atopic children. Clin Exp Allergy 36(3):303–310.  https://doi.org/10.1111/j.1365-2222.2006.02436.x CrossRefPubMedGoogle Scholar
  35. 35.
    Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, Sampson HA (2010) Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 125(3):695–702.  https://doi.org/10.1016/j.jaci.2009.12.017 CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Valenta R, Linhart B, Swoboda I, Niederberger V (2011) Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. Allergy 66(6):775–783.  https://doi.org/10.1111/j.1398-9995.2011.02565.x CrossRefPubMedGoogle Scholar
  37. 37.
    Valenta R, Campana R, Focke-Tejkl M, Niederberger V (2016) Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: lessons from the past and novel mechanisms of action for the future. J Allergy Clin Immunol 137(2):351–357.  https://doi.org/10.1016/j.jaci.2015.12.1299 CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Nowak-Wegrzyn A, Sampson HA (2011) Future therapies for food allergies. J Allergy Clin Immunol 127(3):558–573; quiz 574-555.  https://doi.org/10.1016/j.jaci.2010.12.1098 CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Linhart B, Valenta R (2012) Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives. Vaccine 30(29):4328–4335.  https://doi.org/10.1016/j.vaccine.2011.11.011 CrossRefPubMedGoogle Scholar
  40. 40.
    Pauli G, Larsen TH, Rak S, Horak F, Pastorello E, Valenta R, Purohit A, Arvidsson M, Kavina A, Schroeder JW, Mothes N, Spitzauer S, Montagut A, Galvain S, Melac M, André C, Poulsen LK, Malling HJ (2008) Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol 122(5):951–960.  https://doi.org/10.1016/j.jaci.2008.09.017 CrossRefPubMedGoogle Scholar
  41. 41.
    Nony E, Bouley J, le Mignon M, Lemoine P, Jain K, Horiot S, Mascarell L, Pallardy M, Vincentelli R, Leone P, Roussel A, Batard T, Abiteboul K, Robin B, de Beaumont O, Arvidsson M, Rak S, Moingeon P (2015) Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen-allergic patients. Allergy 70(7):795–804.  https://doi.org/10.1111/all.12622 CrossRefPubMedGoogle Scholar
  42. 42.
    Tourdot S, Airouche S, Berjont N, Moussu H, Betbeder D, Nony E, Bordas-Le Floch V, Baron-Bodo V, Mascarell L, Moingeon P (2013) Efficacy of sublingual vectorized recombinant Bet v 1a in a mouse model of birch pollen allergic asthma. Vaccine 31(23):2628–2637.  https://doi.org/10.1016/j.vaccine.2013.03.041 CrossRefPubMedGoogle Scholar
  43. 43.
    Gomez F, Bogas G, Gonzalez M, Campo P, Salas M, Diaz-Perales A, Rodriguez MJ, Prieto A, Barber D, Blanca M, Torres MJ, Mayorga C (2017) The clinical and immunological effects of Pru p 3 sublingual immunotherapy on peach and peanut allergy in patients with systemic reactions. Clin Exp Allergy 47(3):339–350.  https://doi.org/10.1111/cea.12901 CrossRefPubMedGoogle Scholar
  44. 44.
    Toda M, Reese G, Gadermaier G, Schulten V, Lauer I, Egger M, Briza P, Randow S, Wolfheimer S, Kigongo V, del Mar San Miguel Moncin M, Fötisch K, Bohle B, Vieths S, Scheurer S (2011) Protein unfolding strongly modulates the allergenicity and immunogenicity of Pru p 3, the major peach allergen. J Allergy Clin Immunol 128(5):1022–1030 e1021-1027.  https://doi.org/10.1016/j.jaci.2011.04.020 CrossRefPubMedGoogle Scholar
  45. 45.
    Bolhaar ST et al (2005) A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. Clin Exp Allergy 35(12):1638–1644.  https://doi.org/10.1111/j.1365-2222.2005.02390.x CrossRefPubMedGoogle Scholar
  46. 46.
    Rupa P, Mine Y (2006) Engineered recombinant ovomucoid third domain can desensitize Balb/c mice of egg allergy. Allergy 61(7):836–842.  https://doi.org/10.1111/j.1398-9995.2006.01143.x CrossRefPubMedGoogle Scholar
  47. 47.
    Mine Y, Sasaki E, Zhang JW (2003) Reduction of antigenicity and allergenicity of genetically modified egg white allergen, ovomucoid third domain. Biochem Biophys Res Commun 302(1):133–137.  https://doi.org/10.1016/S0006-291X(03)00117-7 CrossRefPubMedGoogle Scholar
  48. 48.
    Rupa P, Nakamura S, Katayama S, Mine Y (2014) Effects of ovalbumin glycoconjugates on alleviation of orally induced egg allergy in mice via dendritic-cell maturation and T-cell activation. Mol Nutr Food Res 58(2):405–417.  https://doi.org/10.1002/mnfr.201300067 CrossRefPubMedGoogle Scholar
  49. 49.
    Swoboda IB-SA, Linhart B, Verdino P, Keller W, Schulmeister U, Sperr WR, Valent P, Peltre G, Quirce S, Douladiris N, Papadopoulos NG, Valenta R, Spitzauer S (2007) A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol 178(10):6290–6296CrossRefPubMedGoogle Scholar
  50. 50.
    Zuidmeer-Jongejan L, Huber H, Swoboda I, Rigby N, Versteeg SA, Jensen BM, Quaak S, Akkerdaas JH, Blom L, Asturias J, Bindslev-Jensen C, Bernardi ML, Clausen M, Ferrara R, Hauer M, Heyse J, Kopp S, Kowalski ML, Lewandowska-Polak A, Linhart B, Maderegger B, Maillere B, Mari A, Martinez A, Mills ENC, Neubauer A, Nicoletti C, Papadopoulos NG, Portoles A, Ranta-Panula V, Santos-Magadan S, Schnoor HJ, Sigurdardottir ST, Stahl-Skov P, Stavroulakis G, Stegfellner G, Vázquez-Cortés S, Witten M, Stolz F, Poulsen LK, Fernandez-Rivas M, Valenta R, van Ree R (2015) Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy. Int Arch Allergy Immunol 166(1):41–51.  https://doi.org/10.1159/000371657 CrossRefPubMedGoogle Scholar
  51. 51.
    Freidl R, Gstoettner A, Baranyi U, Swoboda I, Stolz F, Focke-Tejkl M, Wekerle T, van Ree R, Valenta R, Linhart B (2017) Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy. J Allergy Clin Immunol 139(6):1897–1905.e1891.  https://doi.org/10.1016/j.jaci.2016.10.018 CrossRefPubMedGoogle Scholar
  52. 52.
    Chatel JM, Bernard H, Clement G, Frobert Y, Batt CA, Gavalchin J, Peltres G, Wal JM (1997) Expression, purification and immunological characterization of recombinant bovine beta-lactoglobulin, a major cow milk allergen. Mol Immunol 33:1113–1118CrossRefGoogle Scholar
  53. 53.
    Chatel JM, Langella P, Adel-Patient K, Commissaire J, Wal JM, Corthier G (2001) Induction of mucosal immune response after intranasal or oral inoculation of mice with Lactococcus lactis producing bovine beta-lactoglobulin. Clin Diagn Lab Immunol 8(3):545–551.  https://doi.org/10.1128/CDLI.8.3.545-551.2001 CrossRefPubMedCentralPubMedGoogle Scholar
  54. 54.
    Chatel JM, Nouaille S, Adel-Patient K, le Loir Y, Boe H, Gruss A, Wal JM, Langella P (2003) Characterization of a Lactococcus lactis strain that secretes a major epitope of bovine beta-lactoglobulin and evaluation of its immunogenicity in mice. Appl Environ Microbiol 69(11):6620–6627.  https://doi.org/10.1128/AEM.69.11.6620-6627.2003 CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Cortes-Perez NG, Ah-Leung S, Bermudez-Humaran LG, Corthier G, Langella P, Wal JM, Adel-Patient K (2009) Allergy therapy by intranasal administration with recombinant Lactococcus lactis producing bovine beta-lactoglobulin. Int Arch Allergy Immunol 150(1):25–31.  https://doi.org/10.1159/000210377 CrossRefPubMedGoogle Scholar
  56. 56.
    de Azevedo MS et al (2013) Immunotherapy of allergic diseases using probiotics or recombinant probiotics. J Appl Microbiol 115(2):319–333.  https://doi.org/10.1111/jam.12174 CrossRefPubMedGoogle Scholar
  57. 57.
    Cocco RR, Järvinen K-M, Sampson HA, Beyer K (2003) Mutational analysis of major, sequential IgE-binding epitopes in αs1-casein, a major cow’s milk allergen. J Allergy Clin Immunol 112(2):433–437.  https://doi.org/10.1067/mai.2003.1617 CrossRefPubMedGoogle Scholar
  58. 58.
    Srivastava K, Li XM, King N, Stanley S, Bannon GA, Burks W, Sampson HA (2002) Immunotherapy with modified peanut allergens in a murine model of peanut allergy. J Allergy Clin Immunol 109(1):S287.  https://doi.org/10.1016/S0091-6749(02)82012-7 CrossRefGoogle Scholar
  59. 59.
    Bannon GA, Cockrell G, Connaughton C, West CM, Helm R, Stanley JS, Rabjohn P, Sampson HA, Burks AW (2001) Engineering, characterization and in vitro efficacy of major peanut allergens for use in immunotherapy. Int Arch Allergy Immunol 124(1-3):70–72.  https://doi.org/10.1159/000053672 CrossRefPubMedGoogle Scholar
  60. 60.
    King N, Helm R, Stanley JS, Vieths S, Lüttkopf D, Hatahet L, Sampson H, Pons L, Burks W, Bannon GA (2005) Allergenic characteristics of a modified peanut allergen. Mol Nutr Food Res 49(10):963–971.  https://doi.org/10.1002/mnfr.200500073 CrossRefPubMedGoogle Scholar
  61. 61.
    Hohman RJ, Dreskin SC (2001) Measuring Degranulation of Mast Cells. Current Protocols in Immunology: John Wiley & Sons, IncGoogle Scholar
  62. 62.
    Rabjohn P, West CM, Connaughton C, Sampson HA, Helm RM, Burks AW, Bannon GA (2002) Modification of peanut allergen Ara h 3: effects on IgE binding and T cell stimulation. Int Arch Allergy Immunol 128(1):15–23.  https://doi.org/10.1159/000057999 CrossRefPubMedGoogle Scholar
  63. 63.
    Gregory JA, Shepley-McTaggart A, Umpierrez M, Hurlburt BK, Maleki SJ, Sampson HA, Mayfield SP, Berin MC (2016) Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice. Plant Biotechnol J 14(7):1541–1550.  https://doi.org/10.1111/pbi.12515 CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Ren C, Zhang Q, Wang G, Ai C, Hu M, Liu X, Tian F, Zhao J, Chen Y, Wang M, Zhang H, Chen W (2014) Modulation of peanut-induced allergic immune responses by oral lactic acid bacteria-based vaccines in mice. Appl Microbiol Biotechnol 98(14):6353–6364.  https://doi.org/10.1007/s00253-014-5678-7 CrossRefPubMedGoogle Scholar
  65. 65.
    Li XM, Srivastava K, Huleatt JW, Bottomly K, Burks AW, Sampson HA (2003) Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model. J Immunol 170(6):3289–3295.  https://doi.org/10.4049/jimmunol.170.6.3289 CrossRefPubMedGoogle Scholar
  66. 66.
    Li X, Huang CK, Schofield BH, Burks AW, Bannon GA, Kim KH, Huang SK, Sampson HA (1999) Strain-dependent induction of allergic sensitization caused by peanut allergen DNA immunization in mice. J Immunol 162:3045–3052PubMedGoogle Scholar
  67. 67.
    Liu Y, Sun Y, Chang LJ, Li N, Li H, Yu Y, Bryce PJ, Grammer LC, Schleimer RP, Zhu D (2013) Blockade of peanut allergy with a novel Ara h 2-Fcgamma fusion protein in mice. J Allergy Clin Immunol 131(1):213–221.e211-215.  https://doi.org/10.1016/j.jaci.2012.10.018 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Allergy, Immunology, and Rheumatology, Department of PediatricsUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations