Omneity® Pellets
All-In-One Vitamin & Mineral Pellet
A novel oral immunotherapy strategy using transgenic barley induces Culicoides allergen-specific immune responses in horses.
Abstract: Insect bite hypersensitivity (IBH) is a seasonal, IgE-mediated allergic dermatitis of horses caused by salivary gland proteins of biting midges ( spp.). Current management relies on relief of clinical signs and on physical protection. In a previous pilot study, healthy horses were fed transgenic barley expressing a allergen via a special spiral bit, which successfully induced allergen-specific antibody responses. Building on this concept, the present study aimed to evaluate a more practical feeding approach, delivering transgenic barley expressing the major allergen Cul o 2p in a feed-compatible paste administered from buckets. Unassigned: Twelve naïve Icelandic horses were randomized into treatment (n=6) and control (n=6) groups. The treatment group received 11.44 g of the major allergen Cul o 2p/horse across three feeding phases. Serum and saliva were analyzed for Cul o 2p-specific antibodies (IgG1, IgG4/7, IgG5, IgA, IgE) by ELISA. IgE-blocking capacity was assessed in pooled serum, and cytokine responses (IL-10, IL-4, IFN-γ) measured after re-stimulation of peripheral blood mononuclear cells (PBMCs). Unassigned: Four of six treated horses produced Cul o 2p-specific IgG1, IgG4/7, and IgA in both serum and saliva. The induced antibodies could partly inhibit IgE binding. Elevated secretion of IFN-γ and IL-10 but no IL-4 secretion was observed in supernatants of re-stimulated PBMCs in treated horses compared to controls, reaching statistical significance for IFN-γ. No Cul o 2p-specific IgE was detected, and no adverse clinical reactions occurred during treatment. Unassigned: The feed-based approach using transgenic barley paste induced Cul o 2p-specific humoral and cellular immune responses in naïve horses, supporting its potential as a scalable and field-feasible platform for prophylactic and therapeutic applications in IBH. Clinical trials in IBH-affected horses are warranted to assess efficacy.
Copyright © 2026 von der Höden, Stefansdottir, Torsteinsdottir, Svansson, Björnsson, Wagner, Mahmuti, Marti and Jonsdottir.
Publication Date: 2026-02-10 PubMed ID: 41743709PubMed Central: PMC12930272DOI: 10.3389/fimmu.2026.1774358Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
Overview
- This study investigates a new oral immunotherapy method using genetically modified barley to induce specific immune responses against insect bite hypersensitivity (IBH) allergens in horses.
- The research evaluates a practical feeding strategy to stimulate protective immune responses without triggering allergic reactions.
Background
- Insect bite hypersensitivity (IBH) is an allergic skin condition in horses caused by immune reactions to proteins from biting midges (Culicoides spp.).
- IBH is characterized by inflammation mediated by IgE antibodies and typically appears in a seasonal pattern when midges are active.
- Current IBH management focuses mainly on alleviating symptoms and physically protecting horses from midge bites, lacking effective preventative or curative treatments.
- Previous pilot studies showed that feeding horses barley genetically modified to express a major Culicoides allergen (Cul o 2p) can successfully induce allergen-specific antibody responses.
Aim of the Study
- To develop and test a more practical, scalable feeding approach using transgenic barley expressing the Cul o 2p allergen for oral immunotherapy in horses.
- To assess immune responses generated by administering this barley in a specially formulated paste given from buckets, instead of using oral devices such as spiral bits.
Methodology
- Twelve naïve Icelandic horses (never exposed to Culicoides allergens before) were randomized into two groups: treatment (6 horses) and control (6 horses).
- The treatment group received a total of 11.44 g of the allergen Cul o 2p via transgenic barley paste during three feeding phases.
- Serum and saliva samples were collected and analyzed for allergen-specific antibodies including IgG subclasses (IgG1, IgG4/7, IgG5), IgA, and IgE using ELISA.
- The ability of induced antibodies to block IgE binding to Cul o 2p was evaluated in pooled serum samples.
- Peripheral blood mononuclear cells (PBMCs) were re-stimulated with the allergen, and cytokine responses (IL-10, IL-4, IFN-γ) were measured to assess cellular immune activity.
- Clinical observations were made throughout to monitor any adverse effects or allergic reactions from the oral immunotherapy.
Results
- Four out of six treated horses developed measurable Cul o 2p-specific antibodies (IgG1, IgG4/7, and IgA) detectable in both serum and saliva.
- These antibodies demonstrated partial inhibition of IgE binding, suggesting potential to block allergic responses.
- Treated horses showed significantly elevated secretion of IFN-γ (a Th1 cytokine) and IL-10 (an anti-inflammatory cytokine) from re-stimulated PBMCs compared to controls, indicating a favorable immune modulation.
- No IL-4, a Th2 cytokine typically promoting allergic responses, was detected, which is desirable to avoid exacerbating allergy.
- Crucially, no Cul o 2p-specific IgE antibodies developed in treated horses and no adverse clinical allergic symptoms were observed during the feeding regimen.
Conclusions and Implications
- Feeding transgenic barley paste expressing the Cul o 2p allergen can induce both humoral (antibody-mediated) and cellular immune responses that may protect against IBH without inducing harmful IgE or clinical allergic reactions.
- This approach is practical for real-world application because it uses a feed-compatible form that horses can ingest easily, making it more scalable than previous methods requiring specialist feeding devices.
- The immune profile observed supports the potential use of this method as both a preventive measure and therapeutic strategy for IBH in horses.
- Further clinical trials in horses actually suffering from IBH are necessary to confirm efficacy and optimize treatment protocols.
Cite This Article
APA
von der Höden FJ, Stefansdottir SB, Torsteinsdottir S, Svansson V, Björnsson JM, Wagner B, Mahmuti D, Marti E, Jonsdottir S.
(2026).
A novel oral immunotherapy strategy using transgenic barley induces Culicoides allergen-specific immune responses in horses.
Front Immunol, 17, 1774358.
https://doi.org/10.3389/fimmu.2026.1774358 Publication
Researcher Affiliations
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- ORF Genetics, Kópavogur, Iceland.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
- Clinical Immunology Group, Division of Neurological Science, Department of Clinical Research-Veterinary Public Health (VPH), Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Clinical Immunology Group, Division of Neurological Science, Department of Clinical Research-Veterinary Public Health (VPH), Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
MeSH Terms
- Animals
- Horses / immunology
- Ceratopogonidae / immunology
- Allergens / immunology
- Allergens / genetics
- Desensitization, Immunologic / methods
- Hordeum / genetics
- Hordeum / immunology
- Immunoglobulin E / immunology
- Immunoglobulin E / blood
- Insect Bites and Stings / immunology
- Insect Bites and Stings / veterinary
- Insect Bites and Stings / therapy
- Horse Diseases / immunology
- Horse Diseases / therapy
- Plants, Genetically Modified / immunology
- Plants, Genetically Modified / genetics
- Insect Proteins / immunology
- Insect Proteins / genetics
- Administration, Oral
- Cytokines / metabolism
- Hypersensitivity / immunology
- Hypersensitivity / veterinary
- Hypersensitivity / therapy
- Female
- Immunoglobulin G / immunology
- Male
Conflict of Interest Statement
J.M. Bjornsson is employed by ORF Genetics Ltd., the company responsible for producing the transgenic barley used in this study. The remaining author(s) declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
This article includes 60 references
- Broström H, Larsson Å, Troedsson M. Allergic dermatitis (sweet itch) of Icelandic horses in Sweden: An epidemiological study.. Equine Veterinary J (1987) 19:229–36.
- Fadok VA, Greiner EC. Equine insect hypersensitivity: skin test and biopsy results correlated with clinical data.. Equine Veterinary J (1990) 22:236–40.
- Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C. Equine insect bite hypersensitivity: what do we know?. Vet Immunol Immunopathol (2012) 147:113–26.
- Marsella R, White S, Fadok VA, Wilson D, Mueller R, Outerbridge C. Equine allergic skin diseases: Clinical consensus guidelines of the World Association for Veterinary Dermatology.. Vet Dermatol (2023) 34:175–208.
- Björnsdóttir S, Sigvaldadóttir J, Broström H, Langvad B, Sigurdsson A. Summer eczema in exported Icelandic horses: influence of environmental and genetic factors.. Acta Vet Scand (2006) 48:3.
- Torsteinsdottir S, Scheidegger S, Baselgia S, Jonsdottir S, Svansson V, Björnsdottir S. A prospective study on insect bite hypersensitivity in horses exported from Iceland into Switzerland.. Acta Vet Scand (2018) 60:69.
- Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD. First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens.. PloS One (2021) 16:e0257819.
- Simonin EM, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Freer H, Tarsillo J. Early allergen introduction overrides allergy predisposition in offspring of horses with Culicoides hypersensitivity.. Front Immunol (2025) 16:1654693.
- Simonin EM, Babasyan S, Tarsillo J, Wagner B. IgE+ plasmablasts predict the onset of clinical allergy.. Front Immunol (2023) 14:1104609.
- Simonin EM, Babasyan S, Wagner B. Peripheral CD23hi/igE+ Plasmablasts secrete igE and correlate with allergic disease severity.. J Immunol (2022) 209:665–74.
- Novotny EN, White SJ, Wilson AD, Stefánsdóttir SB, Tijhaar E, Jonsdóttir S. Component-resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity.. Allergy (2021) 76:1147–57.
- Holaskova E, Galuszka P, Frebort I, Oz MT. Antimicrobial peptide production and plant-based expression systems for medical and agricultural biotechnology.. Biotechnol Adv (2015) 33:1005–23.
- Magnusdottir A, Vidarsson H, Björnsson JM, Örvar BL. Barley grains for the production of endotoxin-free growth factors.. Trends Biotechnol (2013) 31:572–80.
- Jonsdottir S, Stefansdottir SB, Kristinarson SB, Svansson V, Bjornsson JM, Runarsdottir A. Barley produced Culicoides allergens are suitable for monitoring the immune response of horses immunized with E. coli expressed allergens.. Vet Immunol Immunopathol (2018) 201:32–7.
- Jonsdottir S, Torsteinsdottir S, Svansson V, Gudbrandsson J, Stefansdottir SB, Mar Bjornsson J. Comparison of recombinant Culicoides allergens produced in different expression systems for IgE serology of insect bite hypersensitivity in horses of different origins.. Vet Immunol Immunopathol (2021) 238:110289.
- Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J (2015) 8.
- Veneziani I, Landolina N, Ricci B, Rossi O, Moretta L, Maggi E. How the immune system responds to allergy immunotherapy. Biomedicines (2022) 10.
- Jonsdottir S, Hamza E, Janda J, Rhyner C, Meinke A, Marti E. Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study. Vet Immunol Immunopathol (2015) 166:8–21.
- Jonsdottir S, Svansson V, Stefansdottir SB, Schüpbach G, Rhyner C, Marti E. A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A. Vet Immunol Immunopathol (2016) 172:14–20.
- Stefansdottir SB, Jonsdottir S, Kristjansdottir H, Svansson V, Marti E, Torsteinsdottir S. Establishment of a protocol for preventive vaccination against equine insect bite hypersensitivity. Veterinary Immunol Immunopathology (2022) 253:110502.
- Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S. Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity. Front Allergy (2024) 5:1467245.
- Mueller RS, Jensen-Jarolim E, Roth-Walter F, Marti E, Janda J, Seida AA. Allergen immunotherapy in people, dogs, cats and horses – differences, similarities and research needs. Allergy (2018) 73:1989–99.
- Valenta R, Karaulov A, Niederberger V, Zhernov Y, Elisyutina O, Campana R. Allergen extracts for diagnosis and treatment of allergy: is there a future?. J Allergy Clin Immunol Pract (2018) 6:1845–1855.e1842.
- Jonsdottir S, Svansson V, Stefansdottir SB, Mäntylä E, Marti E, Torsteinsdottir S. Oral administration of transgenic barley expressing a Culicoides allergen induces specific antibody response. Equine Vet J (2017) 49:512–8.
- Peeters LM, Janssens S, Goddeeris BM, De Keyser K, Wilson AD, Kaufmann C. Evaluation of an IgE ELISA with Culicoides spp. extracts and recombinant salivary antigens for diagnosis of insect bite hypersensitivity in Warmblood horses. Vet J (2013) 198:141–7.
- Jonsdottir S, Stefansdottir SB, Mirkovitch J, Ziegler A, Torsteinsdottir S, Marti E. Culicoides allergens expressed in insect cells induce sulphidoleukotriene release from peripheral blood leukocytes of horses affected with insect bite hypersensitivity. Front Immunol (2025) 16:1597233.
- Baselgia S, Doherr MG, Mellor P, Torsteinsdottir S, Jermann T, Zurbriggen A. Evaluation of an sulphidoleukotriene release test for diagnosis of insect bite hypersensitivity in horses. Equine Vet J (2006) 38:40–6.
- Hamza E, Doherr MG, Bertoni G, Jungi TW, Marti E. Modulation of allergy incidence in Icelandic horses is associated with a change in IL-4-producing T cells. Int Arch Allergy Immunol (2007) 144:325–37.
- Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses. Veterinary Immunol Immunopathology (2009) 127:242–8.
- Sheoran AS, Timoney JF, Holmes MA, Karzenski SS, Crisman MV. Immunoglobulin isotypes in sera and nasal mucosal secretions and their neonatal transfer and distribution in horses. Am J Vet Res (2000) 61:1099–105.
- Keggan A, Freer H, Rollins A, Wagner B. Production of seven monoclonal equine immunoglobulins isotyped by multiplex analysis. Veterinary Immunol Immunopathology (2013) 153:187–93.
- Schnabel CL, Babasyan S, Freer H, Wagner B. Quantification of equine immunoglobulin A in serum and secretions by a fluorescent bead-based assay. Veterinary Immunol Immunopathology (2017) 188:12–20.
- Wilson AD, Harwood L, Torsteinsdottir S, Marti E. Production of monoclonal antibodies specific for native equine IgE and their application to monitor total serum IgE responses in Icelandic and non-Icelandic horses with insect bite dermal hypersensitivity. Vet Immunol Immunopathol (2006) 112:156–70.
- Moingeon P, Mascarell L. Differences and similarities between sublingual immunotherapy of allergy and oral tolerance. Semin Immunol (2017) 30:52–60.
- Narisety SD, Keet CA. Sublingual vs oral immunotherapy for food allergy: identifying the right approach. Drugs (2012) 72:1977–89.
- Novak N, Bieber T, Allam J-P. Immunological mechanisms of sublingual allergen-specific immunotherapy. Allergy (2011) 66:733–9.
- Kulis MD, Patil SU, Wambre E, Vickery BP. Immune mechanisms of oral immunotherapy. J Allergy Clin Immunol (2018) 141:491–8.
- McGowan EC, Wood RA. Sublingual (SLIT) versus oral immunotherapy (OIT) for food allergy. Curr Allergy Asthma Rep (2014) 14:486.
- Pfaar O, Ankermann T, Augustin M, Bubel P, Böing S, Brehler R. Guideline on allergen immunotherapy in IgE-mediated allergic diseases: S2K Guideline of the German Society of Allergology and Clinical Immunology (DGAKI), Society of Pediatric Allergology and Environmental Medicine (GPA), Medical Association of German Allergologists (AeDA), Austrian Society of Allergology and Immunology (ÖGAI), Swiss Society for Allergology and Immunology (SSAI), German Dermatological Society (DDG), German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), German Society of Pediatrics and Adolescent Medicine (DGKJ), Society of Pediatric Pulmonology (GPP), German Respiratory Society (DGP), German Professional Association of Otolaryngologists (BVHNO), German Association of Paediatric and Adolescent Care Specialists (BVKJ), Federal Association of Pneumologists, Sleep and Respiratory Physicians (BdP), Professional Association of German Dermatologists (BVDD). Allergol Select (2022) 6:167–232.
- Zhang W, Sindher SB, Sampath V, Nadeau K. Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy. Allergo J Int (2018) 27:153–61.
- Janz TA, Jimoh RO, Nguyen SA, Haroun KB, McKinnon B, Siddiqui FN. Exploring side effects of sublingual immunotherapy: A systemic review and meta-analysis. Ear Nose Throat J (2024), 01455613241257827.
- Strobl MR, Demir H, Sánchez Acosta G, Drescher A, Kitzmüller C, Möbs C. The role of IgG and IgG as dominant IgE-blocking antibodies shifts during allergen immunotherapy. J Allergy Clin Immunol (2023) 151:1371–1378.e1375.
- Sahiner UM, Giovannini M, Escribese MM, Paoletti G, Heffler E, Alvaro Lozano M. Mechanisms of allergen immunotherapy and potential biomarkers for clinical evaluation. J personalized Med (2023) 13:845.
- Durham SR, Shamji MH. Allergen immunotherapy: past, present and future. Nat Rev Immunol (2023) 23:317–28.
- Lewis MJ, Wagner B, Woof JM. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies. Mol Immunol (2008) 45:818–27.
- Wagner B. Immunoglobulins and immunoglobulin genes of the horse. Dev Comp Immunol (2006) 30:155–64.
- Wagner B, Goodman LB, Babasyan S, Freer H, Torsteinsdóttir S, Svansson V. Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine. Vaccine (2015) 33:5588–97.
- Larson EM, Wagner B. Viral infection and allergy – What equine immune responses can tell us about disease severity and protection. Mol Immunol (2021) 135:329–41.
- Jentsch MC, Keilhaue A, Wagner B, Rhyner C, Lübke S, Karagulyan M. Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma. Front Immunol (2024) 15:1406794.
- Perkins GA, Wagner B. The development of equine immunity: Current knowledge on immunology in the young horse. Equine Veterinary J (2015) 47:267–74.
- Perkins G, Babasyan S, Stout AE, Freer H, Rollins A, Wimer CL. Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia. Virology (2019) 531:219–32.
- Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA. An equine herpesvirus type 1 (EHV-1) ab4 open reading frame 2 deletion mutant provides immunity and protection from EHV-1 infection and disease. J Virol (2019) 93.
- Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. PloS One (2018) 13:e0206679.
- Raza F, Ivanek R, Freer H, Reiche D, Rose H, Torsteinsdóttir S. Cul o 2 specific IgG3/5 antibodies predicted Culicoides hypersensitivity in a group imported Icelandic horses. BMC Veterinary Res (2020) 16:283.
- Wagner B, Miller WH, Morgan EE, Hillegas JM, Erb HN, Leibold W. IgE and IgG antibodies in skin allergy of the horse. Vet Res (2006) 37:813–25.
- Ziegler A, Hamza E, Jonsdottir S, Rhyner C, Wagner B, Schüpbach G. Longitudinal analysis of allergen-specific IgE and IgG subclasses as potential predictors of insect bite hypersensitivity following first exposure to Culicoides in Icelandic horses. Veterinary Dermatol (2018) 29:51–e22.
- Jay DC, Nadeau KC. Immune mechanisms of sublingual immunotherapy. Curr Allergy Asthma Rep (2014) 14:473.
- Lewis MJ, Wagner B, Irvine RM, Woof JM. IgA in the horse: cloning of equine polymeric Ig receptor and J chain and characterization of recombinant forms of equine IgA. Mucosal Immunol (2010) 3:610–21.
- Jakalski M, Bozek A, Canonica GW. Responders and nonresponders to pharmacotherapy and allergen immunotherapy. Hum Vaccin Immunother (2019) 15:2896–902.
- Qin R, Fu W, Huang R, Xian M, Guo Y, He L. Predicting allergen immunotherapy efficacy based on early maintenance phase response in routine clinical practice. World Allergy Organ J (2024) 17:100986.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
