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Frontiers in allergy2024; 5; 1467245; doi: 10.3389/falgy.2024.1467245

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.
Publication Date: 2024-09-30 PubMed ID: 39403119PubMed Central: PMC11471737DOI: 10.3389/falgy.2024.1467245Google Scholar: Lookup
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  • Journal Article

Summary

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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

ISSN: 2673-6101
NlmUniqueID: 9918227355906676
Country: Switzerland
Language: English
Volume: 5
Pages: 1467245
PII: 1467245

Researcher Affiliations

Graner, Anneli
  • Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Munich, Germany.
Mueller, Ralf S
  • Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Munich, Germany.
Geisler, Johanna
  • 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.
Bogenstätter, Delia
  • Clinical Immunology Group, Division of Neurological Sciences, Department of Clinical Research-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
White, Samuel J
  • Centre for Applied Innovation, York St John University, York, United Kingdom.
Jonsdottir, Sigridur
  • Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
Marti, Eliane
  • 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
  1. 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.
    doi: 10.1016/j.cveq.2020.03.010pubmed: 32534850google scholar: lookup
  2. 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.
    doi: 10.1111/vde.13168pubmed: 37154488google scholar: lookup
  3. 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.
    doi: 10.1186/1751-0147-48-3pmc: PMC1513129pubmed: 16987399google scholar: lookup
  4. 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.
    doi: 10.1017/s1751731107001413pubmed: 22445037google scholar: lookup
  5. Littlewood JD. Incidence of recurrent seasonal pruritus (‘sweet itch’) in British and German shire horses. Vet Rec (1998) 142(3):66–7.
    doi: 10.1136/vr.142.3.66pubmed: 9481844google scholar: lookup
  6. 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.
    doi: 10.1111/all.14556pmc: PMC8246938pubmed: 32780483google scholar: lookup
  7. 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.
  8. 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.
    doi: 10.1111/all.14908pmc: PMC8601105pubmed: 33999439google scholar: lookup
  9. 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.
    doi: 10.1111/all.13464pubmed: 29675865google scholar: lookup
  10. 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.
    doi: 10.1093/jmedent/33.3.458pubmed: 8667395google scholar: lookup
  11. 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.
  12. 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.
    doi: 10.1111/vde.12092pubmed: 24267396google scholar: lookup
  13. 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.
    doi: 10.1111/all.14300pmc: PMC7818275pubmed: 32249442google scholar: lookup
  14. 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.
    doi: 10.1111/vde.13042google scholar: lookup
  15. 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.
    doi: 10.1016/j.vetimm.2016.02.017pubmed: 27032498google scholar: lookup
  16. Rosewich M, Lee D, Zielen S. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis. Hum Vaccin Immunother (2013) 9(7):1523–31.
    doi: 10.4161/hv.24631pubmed: 23584250google scholar: lookup
  17. 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.
    doi: 10.1016/j.tvjl.2016.11.013pubmed: 28093114google scholar: lookup
  18. 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.
    doi: 10.1016/j.vetimm.2022.110502pubmed: 36272211google scholar: lookup
  19. 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.
    doi: 10.1016/j.tvjl.2009.12.030pubmed: 20097587google scholar: lookup
  20. 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.
  21. 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.
    doi: 10.1016/j.vetimm.2015.05.002pubmed: 26004943google scholar: lookup
  22. 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.
    doi: 10.1016/j.vetimm.2006.02.003pubmed: 16574245google scholar: lookup
  23. 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.
    doi: 10.1128/cvi.05522-11pmc: PMC3272919pubmed: 22205656google scholar: lookup
  24. 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.
    doi: 10.1016/j.jaci.2018.01.041pubmed: 29627082google scholar: lookup
  25. Brunner E, Domhof S, Langer F. Nonparametric Analysis of Longitudinal Data in Factorial Experiments. New York, NY: Wiley; (2002).
  26. 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.
    doi: 10.18637/jss.v050.i12pubmed: 0google scholar: lookup
  27. 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.
  28. 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.
    doi: 10.1073/pnas.0803725105pmc: PMC2582048pubmed: 19001265google scholar: lookup
  29. 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.
  30. 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.
    doi: 10.1111/evj.12655pubmed: 27859584google scholar: lookup
  31. 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.
    doi: 10.1111/vde.12493pubmed: 28980353google scholar: lookup
  32. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol (2011) 127(1):18–27.
    doi: 10.1016/j.jaci.2010.11.030pubmed: 21211639google scholar: lookup
  33. 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.
  34. Riek RF. Studies on allergic dermatitis (“Queensland itch”) of the horse. Aust Vet J (1953) 29(7):177–84.

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