Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2003 Jun;111(8):1125–1130. doi: 10.1289/ehp.5813

Assessment of protein allergenicity on the basis of immune reactivity: animal models.

Ian Kimber 1, Rebecca J Dearman 1, Andre H Penninks 1, Leon M J Knippels 1, Robert B Buchanan 1, Bruce Hammerberg 1, Hilary A Jackson 1, Ricki M Helm 1
PMCID: PMC1241562  PMID: 12826485

Abstract

Because of the public concern surrounding the issue of the safety of genetically modified organisms, it is critical to have appropriate methodologies to aid investigators in identifying potential hazards associated with consumption of foods produced with these materials. A recent panel of experts convened by the Food and Agriculture Organization and World Health Organization suggested there is scientific evidence that using data from animal studies will contribute important information regarding the allergenicity of foods derived from biotechnology. This view has given further impetus to the development of suitable animal models for allergenicity assessment. This article is a review of what has been achieved and what still has to be accomplished regarding several different animal models. Progress made in the design and evaluation of models in the rat, the mouse, the dog and in swine is reviewed and discussed.

Full Text

The Full Text of this article is available as a PDF (120.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alving K., Matran R., Lundberg J. M. The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig. Acta Physiol Scand. 1991 Sep;143(1):93–103. doi: 10.1111/j.1748-1716.1991.tb09204.x. [DOI] [PubMed] [Google Scholar]
  2. Astwood J. D., Leach J. N., Fuchs R. L. Stability of food allergens to digestion in vitro. Nat Biotechnol. 1996 Oct;14(10):1269–1273. doi: 10.1038/nbt1096-1269. [DOI] [PubMed] [Google Scholar]
  3. Atkinson H. A., Johnson I. T., Gee J. M., Grigoriadou F., Miller K. Brown Norway rat model of food allergy: effect of plant components on the development of oral sensitization. Food Chem Toxicol. 1996 Jan;34(1):27–32. doi: 10.1016/0278-6915(95)00084-4. [DOI] [PubMed] [Google Scholar]
  4. Bailey M., Miller B. G., Telemo E., Stokes C. R., Bourne F. J. Specific immunological unresponsiveness following active primary responses to proteins in the weaning diet of piglets. Int Arch Allergy Immunol. 1993;101(3):266–271. doi: 10.1159/000236456. [DOI] [PubMed] [Google Scholar]
  5. Bannon Gary, Fu Tong-Jen, Kimber Ian, Hinton Dennis M. Protein digestibility and relevance to allergenicity. Environ Health Perspect. 2003 Jun;111(8):1122–1124. doi: 10.1289/ehp.5812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnett D., Baldo B. A., Howden M. E. Multiplicity of allergens in peanuts. J Allergy Clin Immunol. 1983 Jul;72(1):61–68. doi: 10.1016/0091-6749(83)90053-2. [DOI] [PubMed] [Google Scholar]
  7. Barratt M. E., Strachan P. J., Porter P. Antibody mechanisms implicated in digestive disturbances following ingestion of soya protein in calves and piglets. Clin Exp Immunol. 1978 Feb;31(2):305–312. [PMC free article] [PubMed] [Google Scholar]
  8. Barriga O. O., Ingalls W. L. Potentiation of an IgE-like response to Bordetella bronchiseptica in pigs following Ascaris suum infection. Vet Parasitol. 1984 Nov;16(3-4):343–345. doi: 10.1016/0304-4017(84)90052-9. [DOI] [PubMed] [Google Scholar]
  9. Buchanan B. B., Adamidi C., Lozano R. M., Yee B. C., Momma M., Kobrehel K., Ermel R., Frick O. L. Thioredoxin-linked mitigation of allergic responses to wheat. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5372–5377. doi: 10.1073/pnas.94.10.5372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Burks A. W., Cockrell G., Connaughton C., Guin J., Allen W., Helm R. M. Identification of peanut agglutinin and soybean trypsin inhibitor as minor legume allergens. Int Arch Allergy Immunol. 1994 Oct;105(2):143–149. doi: 10.1159/000236816. [DOI] [PubMed] [Google Scholar]
  11. Butler J. M., Peters J. E., Hirshman C. A., White C. R., Jr, Margolin L. B., Hanifin J. M. Pruritic dermatitis in asthmatic basenji-greyhound dogs: a model for human atopic dermatitis. J Am Acad Dermatol. 1983 Jan;8(1):33–38. doi: 10.1016/s0190-9622(83)70004-6. [DOI] [PubMed] [Google Scholar]
  12. Chamberlain K. W. Clinical signs and diagnosis of atopic disease in the dog. J Small Anim Pract. 1978 Sep;19(9):493–505. doi: 10.1111/j.1748-5827.1978.tb05530.x. [DOI] [PubMed] [Google Scholar]
  13. Criep L. H. Allergy in veterinary medicine. Vet Med Small Anim Clin. 1968 Sep;63(9):855–859. [PubMed] [Google Scholar]
  14. Dearman R. J., Caddick H., Basketter D. A., Kimber I. Divergent antibody isotype responses induced in mice by systemic exposure to proteins: a comparison of ovalbumin with bovine serum albumin. Food Chem Toxicol. 2000 Apr;38(4):351–360. doi: 10.1016/s0278-6915(99)00159-3. [DOI] [PubMed] [Google Scholar]
  15. Dearman R. J., Caddick H., Stone S., Basketter D. A., Kimber I. Characterization of antibody responses induced in rodents by exposure to food proteins: influence of route of exposure. Toxicology. 2001 Oct 30;167(3):217–231. doi: 10.1016/s0300-483x(01)00462-0. [DOI] [PubMed] [Google Scholar]
  16. Dearman R. J., Caddick H., Stone S., Kenna J. G., Basketter D. A., Kimber I. Immunogenic properties of rapidly digested food proteins following gavage exposure of mice: a comparison of ovalbumin with a potato acid phosphatase preparation. Food Chem Toxicol. 2002 May;40(5):625–633. doi: 10.1016/s0278-6915(01)00132-6. [DOI] [PubMed] [Google Scholar]
  17. Dearman R. J., Kimber I. Determination of protein allergenicity: studies in mice. Toxicol Lett. 2001 Mar 31;120(1-3):181–186. doi: 10.1016/s0378-4274(01)00276-4. [DOI] [PubMed] [Google Scholar]
  18. Dréau D., Lallès J. P., Philouze-Romé V., Toullec R., Salmon H. Local and systemic immune responses to soybean protein ingestion in early-weaned pigs. J Anim Sci. 1994 Aug;72(8):2090–2098. doi: 10.2527/1994.7282090x. [DOI] [PubMed] [Google Scholar]
  19. Ermel R. W., Kock M., Griffey S. M., Reinhart G. A., Frick O. L. The atopic dog: a model for food allergy. Lab Anim Sci. 1997 Feb;47(1):40–49. [PubMed] [Google Scholar]
  20. Fornhem C., Dahlbäck M., Kumlin M., Lundberg J. M., Alving K. Effects of local and systemic budesonide on allergen-induced airway reactions in the pig. Br J Pharmacol. 1996 Jun;118(4):989–997. doi: 10.1111/j.1476-5381.1996.tb15497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gold W. M., Kessler G. F., Yu D. Y., Frick O. L. Pulmonary physiologic abnormalities in experimental asthma in dogs. J Appl Physiol. 1972 Oct;33(4):496–501. doi: 10.1152/jappl.1972.33.4.496. [DOI] [PubMed] [Google Scholar]
  22. Halliwell R. E. Atopic disease in the dog. Vet Rec. 1971 Aug 21;89(8):209–214. doi: 10.1136/vr.89.8.209. [DOI] [PubMed] [Google Scholar]
  23. Hankins C. C., Noland P. R., Burks A. W., Jr, Connaughton C., Cockrell G., Metz C. L. Effect of soy protein ingestion on total and specific immunoglobulin G concentrations in neonatal porcine serum measured by enzyme-linked immunosorbent assay. J Anim Sci. 1992 Oct;70(10):3096–3101. doi: 10.2527/1992.70103096x. [DOI] [PubMed] [Google Scholar]
  24. Heppell L. M., Sissons J. W., Banks S. M. Sensitisation of preruminant calves and piglets to antigenic protein in early weaning diets: control of the systemic antibody responses. Res Vet Sci. 1989 Sep;47(2):257–262. [PubMed] [Google Scholar]
  25. Hilton J., Dearman R. J., Basketter D. A., Kimber I. Serological responses induced in mice by immunogenic proteins and by protein respiratory allergens. Toxicol Lett. 1994 Jul;73(1):43–53. doi: 10.1016/0378-4274(94)90187-2. [DOI] [PubMed] [Google Scholar]
  26. Hilton J., Dearman R. J., Sattar N., Basketter D. A., Kimber I. Characteristics of antibody responses induced in mice by protein allergens. Food Chem Toxicol. 1997 Dec;35(12):1209–1218. doi: 10.1016/s0278-6915(97)00119-1. [DOI] [PubMed] [Google Scholar]
  27. Huby R. D., Dearman R. J., Kimber I. Why are some proteins allergens? Toxicol Sci. 2000 Jun;55(2):235–246. doi: 10.1093/toxsci/55.2.235. [DOI] [PubMed] [Google Scholar]
  28. Jackson Hilary A., Hammerberg Bruce. Evaluation of a spontaneous canine model of immunoglobulin E-mediated food hypersensitivity: dynamic changes in serum and fecal allergen-specific immunoglobulin E values relative to dietary change. Comp Med. 2002 Aug;52(4):316–321. [PubMed] [Google Scholar]
  29. Kimber I., Atherton K., Kenna J. G., Dearman R. J. Predictive methods for food allergenicity: perspectives and current status. Toxicology. 2000 Jun 8;147(2):147–150. doi: 10.1016/s0300-483x(00)00225-0. [DOI] [PubMed] [Google Scholar]
  30. Kimber I., Dearman R. J. Food allergy: what are the issues? Toxicol Lett. 2001 Mar 31;120(1-3):165–170. doi: 10.1016/s0378-4274(01)00274-0. [DOI] [PubMed] [Google Scholar]
  31. Knippels L. M., Penninks A. H., Houben G. F. Continued expression of anti-soy protein antibodies in rats bred on a soy protein-free diet for one generation: the importance of dietary control in oral sensitization research. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):815–820. doi: 10.1016/S0091-6749(98)70309-4. [DOI] [PubMed] [Google Scholar]
  32. Knippels L. M., Penninks A. H., Smit J. J., Houben G. F. Immune-mediated effects upon oral challenge of ovalbumin-sensitized Brown Norway rats: further characterization of a rat food allergy model. Toxicol Appl Pharmacol. 1999 May 1;156(3):161–169. doi: 10.1006/taap.1999.8641. [DOI] [PubMed] [Google Scholar]
  33. Knippels L. M., Penninks A. H., Spanhaak S., Houben G. F. Oral sensitization to food proteins: a Brown Norway rat model. Clin Exp Allergy. 1998 Mar;28(3):368–375. doi: 10.1046/j.1365-2222.1998.00242.x. [DOI] [PubMed] [Google Scholar]
  34. Knippels L. M., Penninks A. H., van Meeteren M., Houben G. F. Humoral and cellular immune responses in different rat strains on oral exposure to ovalbumin. Food Chem Toxicol. 1999 Aug;37(8):881–888. doi: 10.1016/s0278-6915(99)00064-2. [DOI] [PubMed] [Google Scholar]
  35. Knippels L. M., van der Kleij H. P., Koppelman S. J., Houben G. F., Penninks A. H. Comparison of antibody responses to hen's egg and cow's milk proteins in orally sensitized rats and food-allergic patients. Allergy. 2000 Mar;55(3):251–258. doi: 10.1034/j.1398-9995.2000.00403.x. [DOI] [PubMed] [Google Scholar]
  36. Knippels Léon M. J., Penninks André H. Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model. Environ Health Perspect. 2003 Feb;111(2):233–238. doi: 10.1289/ehp.5704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Li D. F., Nelssen J. L., Reddy P. G., Blecha F., Klemm R. D., Giesting D. W., Hancock J. D., Allee G. L., Goodband R. D. Measuring suitability of soybean products for early-weaned pigs with immunological criteria. J Anim Sci. 1991 Aug;69(8):3299–3307. doi: 10.2527/1991.6983299x. [DOI] [PubMed] [Google Scholar]
  38. Metcalfe D. D., Astwood J. D., Townsend R., Sampson H. A., Taylor S. L., Fuchs R. L. Assessment of the allergenic potential of foods derived from genetically engineered crop plants. Crit Rev Food Sci Nutr. 1996;36 (Suppl):S165–S186. doi: 10.1080/10408399609527763. [DOI] [PubMed] [Google Scholar]
  39. PATTERSON R. Investigations of spontaneous hypersensitivity of the dog. J Allergy. 1960 Jul-Aug;31:351–363. doi: 10.1016/0021-8707(60)90071-x. [DOI] [PubMed] [Google Scholar]
  40. Patterson R., Mellies C. J., Kelly J. F., Harris K. E. Airway responses of dogs with ragweed and ascaris hypersensitivity. Chest. 1974 May;65(5):488–492. doi: 10.1378/chest.65.5.488. [DOI] [PubMed] [Google Scholar]
  41. Penninks A. H., Knippels L. M. Determination of protein allergenicity: studies in rats. Toxicol Lett. 2001 Mar 31;120(1-3):171–180. doi: 10.1016/s0378-4274(01)00275-2. [DOI] [PubMed] [Google Scholar]
  42. Peters J. E., Hirshman C. A., Malley A. The Basenji-Greyhound dog model of asthma: leukocyte histamine release, serum IgE, and airway response to inhaled antigen. J Immunol. 1982 Sep;129(3):1245–1249. [PubMed] [Google Scholar]
  43. Rees A. S., Lysons R. J., Stokes C. R., Bourne F. J. The effect of parenteral immunisation on antibody production in the pig colon. Vet Immunol Immunopathol. 1989 Nov 30;23(1-2):171–178. doi: 10.1016/0165-2427(89)90119-0. [DOI] [PubMed] [Google Scholar]
  44. Strobel S., Mowat A. M. Immune responses to dietary antigens: oral tolerance. Immunol Today. 1998 Apr;19(4):173–181. doi: 10.1016/s0167-5699(97)01239-5. [DOI] [PubMed] [Google Scholar]
  45. Taylor S. L., Lehrer S. B. Principles and characteristics of food allergens. Crit Rev Food Sci Nutr. 1996;36 (Suppl):S91–118. doi: 10.1080/10408399609527761. [DOI] [PubMed] [Google Scholar]
  46. Teuber Suzanne S., Del Val Gregorio, Morigasaki Susumu, Jung Hye Rim, Eisele Pamela H., Frick Oscar L., Buchanan Bob B. The atopic dog as a model of peanut and tree nut food allergy. J Allergy Clin Immunol. 2002 Dec;110(6):921–927. doi: 10.1067/mai.2002.130056. [DOI] [PubMed] [Google Scholar]
  47. White S. D. Food hypersensitivity in 30 dogs. J Am Vet Med Assoc. 1986 Apr 1;188(7):695–698. [PubMed] [Google Scholar]
  48. Wilson A. D., Stokes C. R., Bourne F. J. Effect of age on absorption and immune responses to weaning or introduction of novel dietary antigens in pigs. Res Vet Sci. 1989 Mar;46(2):180–186. [PubMed] [Google Scholar]
  49. del Val G., Yee B. C., Lozano R. M., Buchanan B. B., Ermel R. W., Lee Y. M., Frick O. L. Thioredoxin treatment increases digestibility and lowers allergenicity of milk. J Allergy Clin Immunol. 1999 Apr;103(4):690–697. doi: 10.1016/s0091-6749(99)70244-7. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES