Immunogenicity of a new allergoid from Felis domesticus
Main Article Content
Keywords
Allergoid, Cat dander, Immunogenicity, Immunotherapy, Allergen-IgE
Abstract
Background: The chemical modification of allergens with glutaraldehyde improves safety while maintaining clinical efficacy, which permits the administration of higher doses of immunotherapy, reducing the risk of adverse reactions. The aim of this study is to evaluate the immunogenic capacity of a new cat dander polymer by immunizing mice and quantifying immunoglobulins in serum, in comparison with the non-modified allergen.
Methods: The study consists of the immunization of three mice groups with the polymerized and the native extract, together with a negative control group. The immunoglobulin levels in serum have been measured by indirect ELISA. By means of the non parametric Mann-Whitney U test, it was determined if there were significant differences in the values of specific antibodies between groups.
Results: The group immunized with the allergoid showed significantly higher specific IgG and IgG1 values to dander allergens and specific IgG to the major allergen Fel d 1, while there were no significant changes in IgG2a and IgE values. These results could be due to a higher immunization dose. The vaccine formulation was based on the optimal defined dose for clinical efficacy of allergen immunotherapy.
Conclusions: This preclinical study carried out with the present assay has established that the allergoid of cat dander extract, as designed for its optimal use in allergen immunotherapy, produces a higher specific IgG than the native extract, in addition to showing significantly higher specific IgG1 levels, evidencing a greater effectiveness in immunization.
References
2. Bauchau V, Durham SR. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J. 2004;24:758-64.
3. Bousquet J, Lockey R, Malling H. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. Allergy. 1998;53:1-42.
4. Satitsuksanoa P, Głobinska ´ A, Jansen K, van de Veen W, Akdis M. Modified allergens for immunotherapy. Curr Allergy Asthma Rep. 2018;18:9.
5. Patterson R, The Robert A. Cooke memorial lecture. Allergen immunotherapy with modified allergens. J Allergy Clin Immunol. 1981;68:85-90.
6. Lu RC, Szilagyi L. Change of reactivity of lysine residues upon actin polymerization. Biochemistry. 1981;20:5914-9.
7. Grammer LC, Patterson R. Development of polymerized allergens for immunotherapy. Asian Pac J Allergy Immunol. 1983;1:55-8.
8. Ohman JL Jr, Lowell FC, Bloch KJ. Allergens of mammalian origin. III. Properties of a major feline allergen. J Immunol. 1974;113:1668-77.
9. Ownby D, Johnson CC. Recent understandings of pet allergies. F1000Res. 2016;5, http://dx.doi.org/10.12688/ f1000research.7044.1, eCollection 2016.
10. Friedhoff L, Meyers D, Marsh D. A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population. J Allergy Clin Immunol. 1984;73:490-9.
11. Kleine-Tebbe J, Kleine-Tebbe A, Jeep S, Schou C, Lowenstein H, Kunkel G. Role of the major allergen (Fel d I) in patients sensitized to cat allergens. Int Arch Allergy Immunol. 1993;100:256-62.
12. Duffort OA, Carreira J, Nitti G, Polo F, Lombardero M. Studies on the biochemical structure of the major cat allergen Felis domesticus I. Mol Immunol. 1991;28:301-9.
13. Kaiser L, Gronlund H, Sandalova T, Ljunggren HG, van HageHamsten M, Achour A, et al. The crystal structure of the major cat allergen Fel d 1, a member of the secretoglobin family. J Biol Chem. 2003;278:37730-5.
14. Grönlund H, Saarne T, Gafvelin G, van Hage M. The major cat allergen, Fel d 1, in diagnosis and therapy. Int Arch Allergy Immunol. 2010;151:265-74.
15. Smith W, Butler A, Hazell L, Chapman M, Pomes A, Nickels D, et al. Fel d 4, a cat lipocalin allergen. Clin Exp Aller. 2004;34:1732-8.
16. Sola JP, Pedreno˜ Y, Cerezo A, Penalver-Mellado ˜ M. Development and characterization of an allergoid of cat dander for immunotherapy. Allergol Immunopathol. 2018;46:491-8.
17. Committee for Medicinal Products for Human Use. Guideline on allergen products: production and quality issues. Eur Med Agency; 2008.
18. European Directorate for the Quality of Medicines (EDQM). In: Council of Europe, editor. Monograph: allergen products -producta allergenica 01/2010: 1063, vol. 6. European Pharmacopoeia; 2010. p. 679-80.
19. US Department of Health and Human Services. Guidance for industry, Q6B specifications: test procedures and acceptance criteria for biotechnological/biological products; 1999. http://www.fda.gov/cder/guidance/Q6Bfnl.PDF
20. Nanda A, O’Connor M, Anand M, Dreskin SC, Zhang L, Hines B, et al. Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. J Allergy Clin Immunol. 2004;114:1339-44.
21. Demoly P, Calderon MA. Dosing and efficacy in specific immunotherapy. Allergy. 2011;66:38-40.
22. Real Decreto 53/2013, de 1 de febrero, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia, núm. 34. Boletín Oficial del Estado; 8 de febrero de 2013. p. 11370-421.
23. Marsh DG, Norman PS, Roebber M, Lichtenstein LM. Studies on allergoids from naturally occurring allergens. III. Preparation of ragweed pollen allergoids by aldehyde modification in two steps. J Allergy Clin Immunol. 1981;68:449-59.
24. Finkelman FD, Wills-Karp M. Usefulness and optimization of mouse models of allergic airway disease. J Allergy Clin Immunol. 2008;121:603-6.
25. Takeda K, Gelfand EW. Mouse models of allergic diseases. Curr Opin Immunol. 2009;21:660-5.
26. Aalberse R, Stapel S, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009;39:469-77.
27. Wachholz PA, Soni NK, Till SJ, Durham SR. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol. 2003;112:915-22.
28. Coffman RL, Seymour BW, Lebman DA, Hiraki DD, Christiansen JA, Shrader B, et al. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988;102:5-28.
29. Yamanishi R, Yusa I, Bando N, Terao J. Adyuvant activity of alum in inducing antigen specific IgE antibodies in BALB/c mice: a reevaluation. Biosci Biotechnol Biochem. 2003;67:166-9.
30. Lund L, Henmar H, Würtzen P, Lund G, Hjortskov N, Larsen J. Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy. Clin Exp Allergy. 2007;37:564-71.
31. Henmar H, Lund G, Lund L, Petersen A, Würtzen P. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin Exp Immunol. 2008;153:316-23.
32. Lopez-Matas MA, Gallego M, Iraola V, Robinson D, Carnes J. Depigmented allergoids reveal new epitopes with capacity to induce IgG blocking antibodies. Biomed Res Int. 2013;2013:284-615.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.