Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity.
Abstract: Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis of horses caused by bites of spp., sharing some common features with human atopic dermatitis. Allergen immunotherapy (AIT) using whole-body extracts has limited efficacy. This study aimed to evaluate AIT with a pool of major recombinant allergens in a prospective, double-blinded, placebo-controlled study. Unassigned: The IBH lesion score was assessed during a pre-treatment year and first treatment year (May-October) in 17 horses and in May and July of a second treatment year. Nine horses were immunized subcutaneously 3× with a combination of nine r-allergens (20 μg each/injection) in alum and monophosphoryl lipid A (MPLA). Eight horses received a placebo. The immunization was repeated twice the following year. The specific antibody response to one of the AIT r-allergens was assessed. Unassigned: In the first treatment year, the decrease in average IBH lesion score was significantly larger in the AIT compared to the placebo group, with 67% of the AIT group and 25% of the placebo horses reaching >50% improvement of the average IBH lesion score. The response to the AIT was enhanced in the 2nd treatment year when 89% of the AIT vs. 14% of the placebo horses showed an improvement ( ≤ 0.01). IgG antibodies of all subclasses were induced, with IgG4/7 showing the most significant differences between groups. The post-AIT sera showed IgE blocking activity. Unassigned: AIT using only a few injections of small amounts of r-allergens in alum and MPLA as immunomodulators seems a promising approach for the treatment of insect bite allergy.
© 2024 Graner, Mueller, Geisler, Bogenstätter, White, Jonsdottir and Marti.
Publication Date: 2024-09-30 PubMed ID: 39403119PubMed Central: PMC11471737DOI: 10.3389/falgy.2024.1467245Google 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.
This research investigates the use of allergen immunotherapy (AIT) with recombinant Culicoides allergens to lessen the effects of insect bite hypersensitivity (IBH) in horses. The results indicate that this method was more effective than a placebo in reducing IBH symptoms, particularly in the second year of treatment.
Research Objective and Methodology
- The study aimed to explore the effectiveness of allergen immunotherapy (AIT) using recombinant allergens from the Culicoides species of insects. These insects are known to cause insect bite hypersensitivity (IBH), a skin disorder in horses triggered by insect bites.
- This research used a double-blinded, placebo-controlled study design to maintain the objectivity of its results.
- The IBH lesion score (a measure of the severity of the skin disorder) of 17 horses was monitored over a pre-treatment year and the first year of treatment.
- Nine horses were injected subcutaneously with a mix of nine recombinant allergens (r-allergens), while the remaining eight received a placebo.
- The treatment and monitoring process was repeated for two subsequent years, and the specific antibody response of the horses to one of the AIT r-allergens was evaluated.
Findings
- In the first year of treatment, the horses that received AIT demonstrated a more significant decrease in their average IBH lesion score compared to those administered the placebo.
- Moreover, 67% of the horses in the AIT group showed a more than 50% improvement in their average IBH lesion score, in contrast to just 25% in the placebo group.
- In the second treatment year, the positive response to AIT increased, with 89% of the horses in the AIT group showing improvement compared to 14% in the placebo group.
- The AIT treatment also resulted in the induction of antibodies for all subclasses, with IgG4/7 showcasing the highest difference between the two groups. Additionally, the sera post-AIT exhibited IgE blocking activity.
Conclusion
- The findings suggest that allergen immunotherapy utilizing small amounts of r-allergens in conjunction with immunomodulators such as alum and monophosphoryl lipid A may be a promising solution for treating insect bite allergies, particularly in horses.
Cite This Article
APA
Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S, Marti E.
(2024).
Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity.
Front Allergy, 5, 1467245.
https://doi.org/10.3389/falgy.2024.1467245 Publication
Researcher Affiliations
- Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Munich, Germany.
- Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Munich, Germany.
- Clinical Immunology Group, Division of Neurological Sciences, Department of Clinical Research-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
- Clinical Immunology Group, Division of Neurological Sciences, Department of Clinical Research-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Centre for Applied Innovation, York St John University, York, United Kingdom.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
- Clinical Immunology Group, Division of Neurological Sciences, Department of Clinical Research-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Conflict of Interest Statement
RM received research support, or consulted or lectured for Nextmune, Synlab, and Heska Laboratories (all of which provide commercial allergen immunotherapy formulations). The remaining authors declare 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 34 references
- Lindgren G, Naboulsi R, Frey R, Solé M. Genetics of skin disease in horses. Vet Clin North Am Equine Pract (2020) 36(2):323–39.
- 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(3):175–208.
- Bjornsdottir S, Sigvaldadottir J, Brostrom H, Langvad B, Sigurdsson A. Summer eczema in exported Icelandic horses: influence of environmental and genetic factors. Acta Vet Scand (2006) 48:3.
- Eriksson S, Grandinson K, Fikse WF, Lindberg L, Mikko S, Broström H. Genetic analysis of insect bite hypersensitivity (summer eczema) in Icelandic horses. Animal (2008) 2(3):360–5.
- Littlewood JD. Incidence of recurrent seasonal pruritus (‘sweet itch’) in British and German shire horses. Vet Rec (1998) 142(3):66–7.
- 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(4):1147–57.
- Cvitas I, Oberhänsli S, Leeb T, Dettwiler M, Müller E, Bruggman R. Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity. PLoS One (2020) 15(4):e0232189.
- Shamji MH, Valenta R, Jardetzky T, Verhasselt V, Durham SR, Würtzen PA. The role of allergen-specific IgE, IgG and IgA in allergic disease. Allergy (2021) 76(12):3627–41.
- 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(10):1989–99.
- Anderson GS, Belton P, Jahren E, Lange H, Kleider N. Immunotherapy trial for horses in British Columbia with Culicoides (Diptera: Ceratopogonidae) hypersensitivity. J Med Entomol (1996) 33(3):458–66.
- Barbet JL, Bevier D, Greiner EC. Specific immunotherapy in the treatment of Culicoides hypersensitive horses: a double-blind study. Equine Vet J (1990) 22(4):232–5.
- Ginel PJ, Hernandez E, Lucena R, Blanco B, Novales M, Mozos E. Allergen-specific immunotherapy in horses with insect bite hypersensitivity: a double-blind, randomized, placebo-controlled study. Vet Dermatol (2014) 25(1):29–e10.
- Dorofeeva Y, Shilovskiy I, Tulaeva I, Focke-Tejkl M, Flicker S, Kudlay D. Past, present, and future of allergen immunotherapy vaccines. Allergy (2021) 76(1):131–49.
- Marti E, Novotny EN, Cvitas I, Ziegler A, Wilson AD, Torsteinsdottir S. Immunopathogenesis and immunotherapy of Culicoides hypersensitivity in horses: an update. Vet Dermatol (2021) 32(6):579–e156.
- 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.
- Rosewich M, Lee D, Zielen S. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis. Hum Vaccin Immunother (2013) 9(7):1523–31.
- Ziegler A, Gerber V, Marti E. In vitro effects of the toll-like receptor agonists monophosphoryl lipid A and CpG-rich oligonucleotides on cytokine production by equine cells. Vet J (2017) 219:6–11.
- Stefansdottir SB, Jonsdottir S, Kristjansdottir H, Svansson V, Marti E, Torsteinsdottir S. Establishment of a protocol for preventive vaccination against equine insect bite hypersensitivity. Vet Immunol Immunopathol (2022) 253:110502.
- Olsén L, Bondesson U, Broström H, Olsson U, Mazogi B, Sundqvist M. Pharmacokinetics and effects of cetirizine in horses with insect bite hypersensitivity. Vet J (2011) 187(3):347–51.
- Friberg Logas. Treatment of Culicoides hypersensitive horses with high-dose n-3 fatty acids: a double-blinded crossover study. Vet Dermatol (1999) 10(2):117–22.
- 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(1–2):8–21.
- 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(3–4):156–70.
- Goodman LB, Wimer C, Dubovi EJ, Gold C, Wagner B. Immunological correlates of vaccination and infection for equine herpesvirus 1. Clin Vaccine Immunol (2012) 19(2):235–41.
- Fettelschoss-Gabriel A, Fettelschoss V, Thoms F, Giese C, Daniel M, Olomski F. Treating insect-bite hypersensitivity in horses with active vaccination against IL-5. J Allergy Clin Immunol (2018) 142(4):1194–205.e3.
- Brunner E, Domhof S, Langer F. Nonparametric Analysis of Longitudinal Data in Factorial Experiments. New York, NY: Wiley; (2002).
- Noguchi K, Gel YR, Brunner E, Konietschke F. nparLD: an R software package for the nonparametric analysis of longitudinal data in factorial experiments. J Stat Softw (2012) 50(12):1–23.
- 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(11):e0257819.
- Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A (2008) 105(46):17908–12.
- 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(3):818–27.
- Jonsdottir S, Svansson V, Stefansdottir SB, Mantyla E, Marti E, Torsteinsdottir S. Oral administration of transgenic barley expressing a Culicoides allergen induces specific antibody response. Equine Vet J (2017) 49(4):512–8.
- 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. Vet Dermatol (2018) 29(1):51–e22.
- Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol (2011) 127(1):18–27.
- Braverman Y. Preferred landing sites of Culicoides species (Diptera: Ceratopogonidae) on a horse in Israel and its relevance to summer seasonal recurrent dermatitis (sweet itch). Equine Vet J (1988) 20(6):426–9.
- Riek RF. Studies on allergic dermatitis (“Queensland itch”) of the horse. Aust Vet J (1953) 29(7):177–84.
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