Development of Immunotherapy for Insect Bite Hypersensitivity in Horses

• Main Author: Jónsdóttir, Sigríður
• Other Authors: Sigurbjörg Þorsteinsdóttir, Vilhjálmur Svansson, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: University of Iceland, School of Health Sciences, Faculty of Medicine 2017
• Subjects: Insect bite hypersensitivity; Horse; Immunotherapy; Allergens; Barley; Exem; Hestar; Ónæmislækningar; Bygg; Doktorsritgerðir; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/297

Insect bite hypersensitivity (IBH) is a type I allergy of horses with production of IgE and release of inflammatory mediators. It is caused by bites of midges of the genus Culicoides. The disease is a recurrent dermatitis characterized by pruritic skin and hair loss, which can result in secondary infections. All breeds of horses can be affected, but horses born in Iceland and exported are more frequently affected than Icelandic horses born abroad. Allergens have been identified at the molecular level from three Culicoides spp., C. sonorensis, C. nubeculosus and C. obsoletus. They have all been produced in E. coli and some in insect cells and barley. The aim of the study was to develop immunotherapy for IBH using vaccination with purified allergens in adjuvants and a method to treat horses via the oral mucosa with transgenic barley expressing allergens. Different injection routes and adjuvants were tested for development of prophylactic immunotherapy. Healthy Icelandic horses were vaccinated intradermally or intralymphatically with a small amount of purified allergens with or without a Th1 adjuvant. The intradermal and the intralymphatic vaccinations with adjuvant resulted in significant generation of allergen specific IgG1 and IgG4/7, the highest response being observed following intralymphatic vaccination. Furthermore, the antibodies produced after intralymphatic vaccination with the allergens in an adjuvant were able to partly inhibit binding of IgE to the allergens, an important mechanism of allergen immunotherapy. The intralymphatic route was employed to compare the immune response induced after vaccination with purified allergens in Alum alone or in a mixture of Alum and Monophosphoryl lipid A (MPLA). The vaccinated horses mounted a strong IgG1 and IgG4/7 response and the antibodies had the capacity to block the binding of IgE to the allergens. The adjuvant groups only differed with regard to the cytokine response but not in the antibody response. Compared to unvaccinated control horses, the IFNγ and IL-10 ...