Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.
Allergens
/ chemistry
Animals
Eosinophils
/ immunology
Epitope Mapping
Epitopes
/ chemistry
Horse Diseases
/ etiology
Horses
Hypersensitivity
/ veterinary
Immunization
Immunoglobulin E
/ immunology
Insect Bites and Stings
/ complications
Interleukin-5
/ chemistry
Leukocyte Count
Models, Molecular
Protein Conformation
Structure-Activity Relationship
Vaccines, Virus-Like Particle
/ administration & dosage
allergic dermatitis
eosinophils
vaccination
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
27
06
2018
revised:
03
10
2018
accepted:
08
10
2018
pubmed:
8
11
2018
medline:
18
4
2020
entrez:
8
11
2018
Statut:
ppublish
Résumé
Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses. Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study. The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMV The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms. Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.
Sections du résumé
BACKGROUND
Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses.
OBJECTIVE
Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study.
METHODS
The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMV
RESULTS
The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms.
CONCLUSION
Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.
Identifiants
pubmed: 30402930
doi: 10.1111/all.13659
pmc: PMC6587569
doi:
Substances chimiques
Allergens
0
Epitopes
0
Interleukin-5
0
Vaccines, Virus-Like Particle
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
572-582Subventions
Organisme : Commission for Technology and Innovation
ID : 25758.1 PFLS-LS
Pays : International
Organisme : Swiss National Science Foundation
ID : CRSII3_154490
Pays : Switzerland
Organisme : Benchmark Vaccines Limited, UK.
Pays : International
Informations de copyright
© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.
Références
Allergy Asthma Immunol Res. 2010 Apr;2(2):87-101
pubmed: 20358022
J Clin Invest. 2016 Sep 1;126(9):3279-95
pubmed: 27548519
Vet Microbiol. 2017 Nov;211:107-111
pubmed: 29102104
Mol Ther. 2016 May;24(5):1003-12
pubmed: 26686385
Med Vet Entomol. 1990 Oct;4(4):375-81
pubmed: 2133005
Nat Rev Drug Discov. 2004 Jan;3(1):81-8
pubmed: 14666113
Vet Rec. 2002 Dec 7;151(23):691-3
pubmed: 12503787
Blood. 1998 Apr 1;91(7):2240-8
pubmed: 9516121
NPJ Vaccines. 2017 Oct 23;2:30
pubmed: 29263885
Protein Sci. 2012 Jun;21(6):850-64
pubmed: 22528658
J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):167-74
pubmed: 25754717
Equine Vet J. 1990 Jul;22(4):236-40
pubmed: 1976506
Nat Protoc. 2012 Jul 19;7(8):1511-22
pubmed: 22814390
Exp Hematol. 1992 Feb;20(2):229-34
pubmed: 1544392
J Comp Pathol. 1994 Feb;110(2):145-52
pubmed: 8040382
Equine Vet J. 1983 Jul;15(3):266-72
pubmed: 6884318
Immunity. 1996 Jan;4(1):15-24
pubmed: 8574848
Int Immunol. 1999 Dec;11(12):1935-44
pubmed: 10590259
J Exp Med. 1995 Oct 1;182(4):1169-74
pubmed: 7561691
Vet Immunol Immunopathol. 2012 Jun 30;147(3-4):113-26
pubmed: 22575371
PLoS One. 2018 Jul 31;13(7):e0201570
pubmed: 30063758
Eur J Immunol. 2002 Nov;32(11):3305-14
pubmed: 12555676
Vet Rec. 1998 Aug 15;143(7):189-93
pubmed: 9762759
J Allergy Clin Immunol. 2018 Oct;142(4):1194-1205.e3
pubmed: 29627082
Expert Rev Vaccines. 2016 May;15(5):561-3
pubmed: 26919571
J Med Entomol. 1996 May;33(3):458-66
pubmed: 8667395
Vet Rec. 1983 May 28;112(22):521-4
pubmed: 6879963
J Med Entomol. 1991 Sep;28(5):685-93
pubmed: 1941937
Allergy. 2019 Mar;74(3):572-582
pubmed: 30402930
Front Med (Lausanne). 2018 Apr 06;5:49
pubmed: 29682504
J Anim Sci. 2001 Oct;79(10):2524-35
pubmed: 11721830
Equine Vet J. 1978 Oct;10(4):243-8
pubmed: 738265
Cytokine. 2002 Jul 7;19(1):27-30
pubmed: 12200110