Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study.
Abstract: Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of midges (Culicoides spp.). IgE-mediated reactions are often involved in the pathogenesis of this disease. IBH does not occur in Iceland due to the absence of Culicoides, but it occurs with a high frequency in Icelandic horses exported to mainland Europe, where Culicoides are present. We hypothesize that immunization with the Culicoides allergens before export could reduce the incidence of IBH in exported Icelandic horses. The aim of the present study was therefore to compare intradermal and intralymphatic vaccination using four purified recombinant allergens, in combination with a Th1 focusing adjuvant. Twelve horses were vaccinated three times with 10μg of each of the four recombinant Culicoides nubeculosus allergens. Six horses were injected intralymphatically, three with and three without IC31(®), and six were injected intradermally, in the presence or absence of IC31(®). Antibody responses were measured by immunoblots and ELISA, potential sensitization in a sulfidoleukotriene release test and an intradermal test, cytokine and FoxP3 expression with real time PCR following in vitro stimulation of PBMC. Immunization with the r-allergens induced a significant increase in levels of r-allergen-specific IgG1, IgG1/3, IgG4/7, IgG5 and IgG(T). Application of the r-allergens in IC31(®) adjuvant resulted in a significantly higher IgG1, IgG1/3, IgG4/7 allergen-specific response. Intralymphatic injection was slightly more efficient than intradermal injection, but the difference did not reach significance. Testing of the blocking activity of the sera from the horses immunized intralymphatically with IC31(®) showed that the generated IgG antibodies were able to partly block binding of serum IgE from an IBH-affected horse to these r-allergens. Furthermore, IgG antibodies bound to protein bands on blots of C. nubeculosus salivary gland extract. No allergen-specific IgE was induced and there was no indication of induction of IgE-mediated reactions, as horses neither responded to Culicoides extract stimulation in a sulfidoleukotriene release test, nor developed a relevant immediate hypersensitivity reaction to the recombinant allergens in skin test. IL-4 expression was significantly higher in horses vaccinated intralymphatically without IC31(®), as compared to horses intradermally vaccinated with IC31(®). Both routes gave higher IL-10 expression with IC31(®). Both intralymphatic and intradermal vaccination of horses with recombinant allergens in IC31(®) adjuvant induced an immune response without adverse effects and without IgE production. The horses were not sensitized and produced IgG that could inhibit allergen-specific IgE binding. We therefore conclude that both the injection routes and the IC31(®) adjuvant are strong candidates for further development of immunoprophylaxis and therapy in horses.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication Date: 2015-05-15 PubMed ID: 26004943DOI: 10.1016/j.vetimm.2015.05.002Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates a potential immunization method to prevent a horse allergy known as Insect Bite Hypersensitivity (IBH), triggered by bites from midges. The study finds that intradermal and intralymphatic vaccinations using specific allergens could help protect Icelandic horses exported to mainland Europe, where the causative insects are prevalent.
Research Rationale and Methodology
- This research was conducted based on the observation that Icelandic horses exported to mainland Europe often developed Insect Bite Hypersensitivity (IBH), conditioned by the presence of midges (Culicoides spp.) in mainland Europe, which are absent in Iceland.
- Researchers hypothesized that immunizing horses with allergens found in Culicoides could help decrease the incidence of IBH in exported Icelandic horses.
- The study involved administering intradermal and intralymphatic vaccinations to twelve horses using four purified recombinant allergens, combined with a Th1 focusing adjuvant. The horses received three vaccinations containing 10μg of each allergen.
- Six horses received intralymphatic injections, in the presence or absence of an adjuvant called IC31(®), while another six received intradermal injections, with or without IC31(®).
- The results were measured by evaluating antibody responses, potential sensitization, cytokine and FoxP3 expression following stimulation.
Key Findings
- The immunization resulted in a significant increase in levels of specific IgG antibodies responsible for fighting the allergens.
- The use of IC31(®) adjuvant, an immune response enhancer, resulted in significantly higher allergen-specific antibody responses.
- The intralymphatic injection method was marginally more effective than the intradermal method, though the difference was not statistically significant.
- The IgG antibodies produced in horses were able to partially inhibit the binding of serum IgE, an antibody causing allergic reactions, to the allergens.
- No allergen-specific IgE was produced; hence there was no allergic reaction. This shows the vaccination against the allergens was not sensitizing the horses.
- Both vaccination methods, along with the adjuvant IC31(®), successfully stimulated an immune response without causing any adverse effects or IgE production.
Conclusion of the Study
- The research concluded that both injection methods, intradermal and intralymphatic, as well as the IC31(®) adjuvant, are potent candidates for further development in creating preventive strategies and treatments for horses.
- It suggests these approaches could be instrumental in reducing allergic reactions in horses, specifically IBH, without inducing the production of allergen-specific IgE, the primary cause of allergic reactions.
Cite This Article
APA
Jonsdottir S, Hamza E, Janda J, Rhyner C, Meinke A, Marti E, Svansson V, Torsteinsdottir S.
(2015).
Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study.
Vet Immunol Immunopathol, 166(1-2), 8-21.
https://doi.org/10.1016/j.vetimm.2015.05.002 Publication
Researcher Affiliations
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Keldnavegur 3, 112 Reykjavik, Iceland. Electronic address: sij9@hi.is.
- Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Berne, Länggassstrasse 124, 3012 Berne, Switzerland.
- Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Berne, Länggassstrasse 124, 3012 Berne, Switzerland.
- Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
- Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
- Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Berne, Länggassstrasse 124, 3012 Berne, Switzerland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Keldnavegur 3, 112 Reykjavik, Iceland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Keldnavegur 3, 112 Reykjavik, Iceland.
MeSH Terms
- Allergens / immunology
- Animals
- Drug Combinations
- Horses
- Hypersensitivity / prevention & control
- Immunization
- Immunoglobulin G / blood
- Immunoglobulin G / classification
- Insect Bites and Stings / immunology
- Oligodeoxyribonucleotides / pharmacology
- Oligopeptides / pharmacology
- Pilot Projects
- Recombinant Proteins / immunology
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