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Published in: BMC Immunology 1/2017

Open Access 01-12-2017 | Research article

In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy

Authors: María Morales, Mayte Gallego, Victor Iraola, Marta Taulés, Eliandre de Oliveira, Raquel Moya, Jerónimo Carnés

Published in: BMC Immunology | Issue 1/2017

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Abstract

Background

Allergy to cat epithelia is highly prevalent, being the major recommendation for allergy sufferers its avoidance. However, this is not always feasible. Allergen specific immunotherapy is therefore recommended for these patients. The use of polymerized allergen extracts, allergoids, would allow to achieve the high allergen doses suggested to be effective while maintaining safety.

Results

Cat native extract and its depigmented allergoid were manufactured and biochemically and immunochemically characterized. Protein and chromatographic profiles showed significant modification of the depigmented allergoid with respect to its corresponding native extract. However, the presence of different allergens (Fel d 1, Fel d 2, Fel d 3, Fel d 4 and Fel d 7) was confirmed in the allergoid. Differences in IgE-binding capacity were observed as loss of biological potency and lower stability of the IgE-allergen complex on surface plasmon resonance. The allergoid induced production of IgG antibodies able to block IgE-binding to native extract. Finally, studies carried out with peripheral-blood mononuclear cells from cat allergic patients showed that the allergoid induced IFN-γ and IL-10 production similar to that induced by native extract.

Conclusions

Cat depigmented allergoid induced production of cytokines involved in a Th1 and Treg response, was able to induce production of IgG-antibodies that blocks IgE-binding to cat native extract, and showed reduced interaction with IgE, suggesting greater safety than native extract while maintaining in vitro efficacy.
Literature
1.
go back to reference Heinzerling LM, Burbach GJ, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet J, Bousquet-Rouanet L, Bousquet PJ, Bresciani M, Bruno A, Burney P, Canonica GW, Darsow U, Demoly P, Durham S, Fokkens WJ, Giavi S, Gjomarkaj M, Gramiccioni C, Haahtela T, Kowalski ML, Magyar P, Murakozi G, Orosz M, Papadopoulos NG, Rohnelt C, Stingl G, Todo-Bom A, von Mutius E, Wiesner A, Wohrl S, Zuberbier T. Ga (2) len skin test study i: Ga (2) len harmonization of skin prick testing: Novel sensitization patterns for inhalant allergens in europe. Allergy. 2009;64:1498–506.CrossRefPubMed Heinzerling LM, Burbach GJ, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet J, Bousquet-Rouanet L, Bousquet PJ, Bresciani M, Bruno A, Burney P, Canonica GW, Darsow U, Demoly P, Durham S, Fokkens WJ, Giavi S, Gjomarkaj M, Gramiccioni C, Haahtela T, Kowalski ML, Magyar P, Murakozi G, Orosz M, Papadopoulos NG, Rohnelt C, Stingl G, Todo-Bom A, von Mutius E, Wiesner A, Wohrl S, Zuberbier T. Ga (2) len skin test study i: Ga (2) len harmonization of skin prick testing: Novel sensitization patterns for inhalant allergens in europe. Allergy. 2009;64:1498–506.CrossRefPubMed
2.
go back to reference Arbes Jr SJ, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the us population: Results from the third national health and nutrition examination survey. J Allergy Clin Immunol. 2005;116:377–83.CrossRefPubMed Arbes Jr SJ, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the us population: Results from the third national health and nutrition examination survey. J Allergy Clin Immunol. 2005;116:377–83.CrossRefPubMed
3.
go back to reference Stemeseder T, Klinglmayr E, Moser S, Lueftenegger L, Lang R, Himly M, Oostingh GJ, Zumbach J, Bathke AC, Hawranek T, Gadermaier G: Cross-sectional study on allergic sensitization of austrian adolescents using molecule-based ige profiling. Allergy. 2016. doi: 10.1111/all.13071. [Epub ahead of print] Stemeseder T, Klinglmayr E, Moser S, Lueftenegger L, Lang R, Himly M, Oostingh GJ, Zumbach J, Bathke AC, Hawranek T, Gadermaier G: Cross-sectional study on allergic sensitization of austrian adolescents using molecule-based ige profiling. Allergy. 2016. doi: 10.​1111/​all.​13071. [Epub ahead of print]
4.
go back to reference Alvarez-Cuesta E, Berges-Gimeno P, Gonzalez-Mancebo E, Fernandez-Caldas E, Cuesta-Herranz J, Casanovas M. Sublingual immunotherapy with a standardized cat dander extract: Evaluation of efficacy in a double blind placebo controlled study. Allergy. 2007;62:810–7.CrossRefPubMed Alvarez-Cuesta E, Berges-Gimeno P, Gonzalez-Mancebo E, Fernandez-Caldas E, Cuesta-Herranz J, Casanovas M. Sublingual immunotherapy with a standardized cat dander extract: Evaluation of efficacy in a double blind placebo controlled study. Allergy. 2007;62:810–7.CrossRefPubMed
5.
go back to reference Varney VA, Edwards J, Tabbah K, Brewster H, Mavroleon G, Frew AJ. Clinical efficacy of specific immunotherapy to cat dander: A double-blind placebo-controlled trial. Clin Exp Allergy. 1997;27:860–7.CrossRefPubMed Varney VA, Edwards J, Tabbah K, Brewster H, Mavroleon G, Frew AJ. Clinical efficacy of specific immunotherapy to cat dander: A double-blind placebo-controlled trial. Clin Exp Allergy. 1997;27:860–7.CrossRefPubMed
6.
go back to reference Ewbank PA, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson HS. A double-blind, placebo-controlled immunotherapy dose–response study with standardized cat extract. J Allergy Clin Immunol. 2003;111:155–61.CrossRefPubMed Ewbank PA, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson HS. A double-blind, placebo-controlled immunotherapy dose–response study with standardized cat extract. J Allergy Clin Immunol. 2003;111:155–61.CrossRefPubMed
7.
go back to reference Demoly P, Calderon MA. Dosing and efficacy in specific immunotherapy. Allergy. 2011;66 Suppl 95:38–40.CrossRefPubMed Demoly P, Calderon MA. Dosing and efficacy in specific immunotherapy. Allergy. 2011;66 Suppl 95:38–40.CrossRefPubMed
8.
go back to reference Ibarrola I, Sanz ML, Gamboa PM, Mir A, Benahmed D, Ferrer A, Arilla MC, Martinez A, Asturias JA. Biological characterization of glutaraldehyde-modified Parietaria judaica pollen extracts. Clin Exp Allergy. 2004;34:303–9. Ibarrola I, Sanz ML, Gamboa PM, Mir A, Benahmed D, Ferrer A, Arilla MC, Martinez A, Asturias JA. Biological characterization of glutaraldehyde-modified Parietaria judaica pollen extracts. Clin Exp Allergy. 2004;34:303–9.
9.
go back to reference 9 Carnés Sánchez J: Process for producing an allergen extract. WO 2011/098569; PCT/EP2011/052049 9 Carnés Sánchez J: Process for producing an allergen extract. WO 2011/098569; PCT/EP2011/052049
10.
go back to reference Gallego MT, Iraola V, Himly M, Robinson DS, Badiola C, Garcia-Robaina JC, Briza P, Carnes J. Depigmented and polymerised house dust mite allergoid: Allergen content, induction of IgG4 and clinical response. Int Arch Allergy Immunol. 2010;153:61–9. Gallego MT, Iraola V, Himly M, Robinson DS, Badiola C, Garcia-Robaina JC, Briza P, Carnes J. Depigmented and polymerised house dust mite allergoid: Allergen content, induction of IgG4 and clinical response. Int Arch Allergy Immunol. 2010;153:61–9.
11.
go back to reference Pfaar O, Sager A, Robinson DS. Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: A retrospective study of 2927 paediatric patients. Pediatr Allergy Immunol. 2015;26:280–6.CrossRefPubMedPubMedCentral Pfaar O, Sager A, Robinson DS. Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: A retrospective study of 2927 paediatric patients. Pediatr Allergy Immunol. 2015;26:280–6.CrossRefPubMedPubMedCentral
12.
go back to reference Gronlund 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. Gronlund 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.
13.
go back to reference Couroux P, Patel D, Armstrong K, Larche M, Hafner RP. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects. Clin Exp Allergy. 2015;45:974–81.CrossRefPubMed Couroux P, Patel D, Armstrong K, Larche M, Hafner RP. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects. Clin Exp Allergy. 2015;45:974–81.CrossRefPubMed
14.
go back to reference Siman IL, de Aquino LM, Ynoue LH, Miranda JS, Pajuaba AC, Cunha-Junior JP, Silva DA, Taketomi EA. Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: An in vitro study. Clin Dev Immunol. 2013;2013:657424. Siman IL, de Aquino LM, Ynoue LH, Miranda JS, Pajuaba AC, Cunha-Junior JP, Silva DA, Taketomi EA. Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: An in vitro study. Clin Dev Immunol. 2013;2013:657424.
15.
go back to reference Iraola V, Gallego MT, Taules M, Carnes J. Measurement of immunoglobulin e interaction with allergen extracts by surface plasmon resonance biosensor analysis. Ann Allergy Asthma Immunol. 2013;111:228–9.CrossRefPubMed Iraola V, Gallego MT, Taules M, Carnes J. Measurement of immunoglobulin e interaction with allergen extracts by surface plasmon resonance biosensor analysis. Ann Allergy Asthma Immunol. 2013;111:228–9.CrossRefPubMed
16.
go back to reference Casanovas M, Maranon F, Bel I. Comparison of skin-prick test assay and reverse enzyme immunoassay competition (REINA-C) for biological activity of allergens. Clin Exp Allergy. 1994;24:134–9. Casanovas M, Maranon F, Bel I. Comparison of skin-prick test assay and reverse enzyme immunoassay competition (REINA-C) for biological activity of allergens. Clin Exp Allergy. 1994;24:134–9.
17.
go back to reference 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;2013:284615. 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;2013:284615.
18.
go back to reference Van Metre Jr TE, Marsh DG, Adkinson Jr NF, Kagey-Sobotka A, Khattignavong A, Norman Jr PS, Rosenberg GL. Immunotherapy for cat asthma. J Allergy Clin Immunol. 1988;82:1055–68.CrossRefPubMed Van Metre Jr TE, Marsh DG, Adkinson Jr NF, Kagey-Sobotka A, Khattignavong A, Norman Jr PS, Rosenberg GL. Immunotherapy for cat asthma. J Allergy Clin Immunol. 1988;82:1055–68.CrossRefPubMed
19.
go back to reference Jutel M, Akdis CA. Immunological mechanisms of allergen-specific immunotherapy. Allergy. 2011;66:725–32.CrossRefPubMed Jutel M, Akdis CA. Immunological mechanisms of allergen-specific immunotherapy. Allergy. 2011;66:725–32.CrossRefPubMed
20.
go back to reference Matsuoka T, Shamji MH, Durham SR. Allergen immunotherapy and tolerance. Allergol Int. 2013;62:403–13.CrossRefPubMed Matsuoka T, Shamji MH, Durham SR. Allergen immunotherapy and tolerance. Allergol Int. 2013;62:403–13.CrossRefPubMed
21.
go back to reference James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR. Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol. 2011;127:509–16. e501-505.CrossRefPubMed James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR. Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol. 2011;127:509–16. e501-505.CrossRefPubMed
22.
go back to reference Carnes J, Himly M, Gallego M, Iraola V, Robinson DS, Fernandez-Caldas E, Briza P. Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba. Clin Exp Allergy. 2009;39:426–34. Carnes J, Himly M, Gallego M, Iraola V, Robinson DS, Fernandez-Caldas E, Briza P. Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba. Clin Exp Allergy. 2009;39:426–34.
23.
go back to reference Andersson TN, Ekman GJ, Gronlund H, Buentke E, Eriksson TL, Scheynius A, Van Hage-Hamsten M, Gafvelin G. A novel adjuvant-allergen complex, CBP-rFel d 1, induces up-regulation of CD86 expression and enhances cytokine release by human dendritic cells in vitro. Immunology. 2004;113:253–9. Andersson TN, Ekman GJ, Gronlund H, Buentke E, Eriksson TL, Scheynius A, Van Hage-Hamsten M, Gafvelin G. A novel adjuvant-allergen complex, CBP-rFel d 1, induces up-regulation of CD86 expression and enhances cytokine release by human dendritic cells in vitro. Immunology. 2004;113:253–9.
Metadata
Title
In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy
Authors
María Morales
Mayte Gallego
Victor Iraola
Marta Taulés
Eliandre de Oliveira
Raquel Moya
Jerónimo Carnés
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2017
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-017-0193-0

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