Refinement of the equine influenza model in the natural host: A meta-analysis to determine the benefits of individual nebulisation for experimental infection and vaccine evaluation in the face of decreased strain pathogenicity.
Abstract: Equine Influenza (EI) is an important respiratory disease of horses caused by H3N8 equine influenza viruses (EIV). Vaccination is a key strategy to prevent or control this disease. However, EIV undergoes continuous antigenic drift and whilst numerous EI vaccines are commercially available worldwide, an accurate evaluation of their efficacy is frequently required through clinical trials conducted in the natural host. Room nebulisation is one of the chosen methods to challenge horses during EI vaccine studies. A potential decreased pathogenicity observed with recent Florida Clade 2 (FC2) EIV isolates have increased the heterogeneity of the clinical response and virus shedding measured after infection by room nebulisation, which reduced the statistical power of studies. Our objectives were to compare clinical and virological parameters following experimental infection with several different EIV strains and to confirm that individual nebulisation is a model refinement that prevents an increase of the number of animals per group. This study is a retrospective comparison and meta-analysis of clinical and virological results collected from 9 independent EIV infection studies in the natural host. Naïve Welsh mountain ponies were experimentally infected by room or individual nebulisation with FC2 EIV strains, including A/equine/Richmond/1/07 (R/07), A/equine/East Renfrewshire/11 (ER/11), A/equine/Cambremer/1/2012 (C/12) and A/equine/Northamptonshire/1/13 (N/1/13). The retrospective meta-analysis confirmed a decreased pathogenicity of the EIV ER/11 and C/12 strains when compared with R/07. Experimental infection by individual nebulisation improved the clinical and virological parameters induced by recent FC2 strains, when compared with conventional room nebulisation. In conclusion, individual nebulisation offers a better control of the challenge dose administered and a greater homogeneity of the response measured in control animals. This in turn, helps maintain the number of animals per group to the minimum necessary required to obtain meaningful results in vaccine efficacy studies, which adheres to the 3Rs (Replacement, Reduction and Refinement) principles.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication Date: 2017-10-10 PubMed ID: 29102112DOI: 10.1016/j.vetmic.2017.10.010Google Scholar: Lookup
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- Journal Article
- Meta-Analysis
Summary
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The study focuses on the investigation of efficacy of individual nebulisation in administering Equine Influenza (EI) vaccine and comparing it to traditional room nebulisation method. The research also analyzes the decreased pathogenicity of recent Florida Clade 2 (FC2) EIV strains and its impact on the statistical power of the studies.
Introduction to the Study
- This research centers around Equine Influenza (EI), a major respiratory disease in horses caused by the H3N8 equine influenza viruses (EIV). Vaccination is a crucial prevention or control strategy for EI.
- However, the virus continually adapts through antigenic drift. This necessitates frequent efficacy evaluations of the numerous commercially available EI vaccines through clinical trials conducted on the natural host, i.e., the horses.
- The study also discusses challenges faced in EI vaccine studies due to potential decrease in pathogenicity observed with recent Florida Clade 2 (FC2) EIV isolates. This decrease led to more diverse clinical responses and virus shedding measured after infection by room nebulisation, thus reducing the statistical power of the studies.
Goals of the Study
- The research aimed at comparing clinical and virological parameters after experimental infection with different EIV strains. This was to confirm the effectiveness of individual nebulisation as a model refinement.
- It also aimed to ensure that the number of animals per group didn’t unnecessarily increase.
Methodology and Outcome
- The study is a retrospective comparison and meta-analysis of clinical and virological results drawn from 9 independent EIV infection studies conducted on the natural host.
- Naïve Welsh mountain ponies were experimentally infected by either room or individual nebulisation with FC2 EIV strains. These include strains such as A/equine/Richmond/1/07 (R/07), A/equine/East Renfrewshire/11 (ER/11), etc.
- The analysis confirmed decreased pathogenicity of the EIV ER/11 and C/12 strains when compared to R/07. The infection using individual nebulisation enhanced the clinical and virological parameters induced by recent FC2 strains in comparison to the room nebulisation.
Conclusion
- The research conclusions advocate the benefits of individual nebulisation as it provides better control of the challenge dose administered. It also results in greater uniformity in the response measured in control animals. This helps to maintain the number of animals per group to the minimum necessary to achieve meaningful results in vaccine efficacy studies.
- In adherence to the 3Rs (Replacement, Reduction and Refinement) principles, individual nebulisation supports responsible scientific research by reducing the number of animals employed in experiments.
Cite This Article
APA
Garrett D, Montesso F, Fougerolle S, Lopez-Alvarez MR, Birand I, De Bock M, Huang CM, Legrand L, Pronost S, Paillot R.
(2017).
Refinement of the equine influenza model in the natural host: A meta-analysis to determine the benefits of individual nebulisation for experimental infection and vaccine evaluation in the face of decreased strain pathogenicity.
Vet Microbiol, 211, 150-159.
https://doi.org/10.1016/j.vetmic.2017.10.010 Publication
Researcher Affiliations
- Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, CB8 7UU, Kentford Newmarket, United Kingdom.
- Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, CB8 7UU, Kentford Newmarket, United Kingdom.
- Frank Duncombe Laboratory-LABÉO, 1 Route De Rosel, 14053 CAEN Cedex 4, France; University of Caen Basse-Normandie, 14000 Caen, France; Unité de Recherche Risques Microbiens (U2RM), EA 4655, and Chair of Excellence ˝ Equine Immunology˝, 14032 Caen, France; Hippolia Foundation, La Maison du cheval, 6 Avenue du Maréchal Montgomery, 14000 Caen, France; BioTARGen, University of Caen Normandy, 14053 Caen cedex 4, France.
- Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, CB8 7UU, Kentford Newmarket, United Kingdom.
- Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, CB8 7UU, Kentford Newmarket, United Kingdom.
- Elanco Animal Health, Plantin en Moretuslei, B-2018, Antwerpen, Belgium.
- Elanco Animal Health, Greenfield, IN, USA.
- Frank Duncombe Laboratory-LABÉO, 1 Route De Rosel, 14053 CAEN Cedex 4, France; University of Caen Basse-Normandie, 14000 Caen, France; Unité de Recherche Risques Microbiens (U2RM), EA 4655, and Chair of Excellence ˝ Equine Immunology˝, 14032 Caen, France; Hippolia Foundation, La Maison du cheval, 6 Avenue du Maréchal Montgomery, 14000 Caen, France; BioTARGen, University of Caen Normandy, 14053 Caen cedex 4, France.
- Frank Duncombe Laboratory-LABÉO, 1 Route De Rosel, 14053 CAEN Cedex 4, France; University of Caen Basse-Normandie, 14000 Caen, France; Unité de Recherche Risques Microbiens (U2RM), EA 4655, and Chair of Excellence ˝ Equine Immunology˝, 14032 Caen, France; Hippolia Foundation, La Maison du cheval, 6 Avenue du Maréchal Montgomery, 14000 Caen, France; BioTARGen, University of Caen Normandy, 14053 Caen cedex 4, France.
- Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, CB8 7UU, Kentford Newmarket, United Kingdom; Frank Duncombe Laboratory-LABÉO, 1 Route De Rosel, 14053 CAEN Cedex 4, France; University of Caen Basse-Normandie, 14000 Caen, France; Unité de Recherche Risques Microbiens (U2RM), EA 4655, and Chair of Excellence ˝ Equine Immunology˝, 14032 Caen, France; Hippolia Foundation, La Maison du cheval, 6 Avenue du Maréchal Montgomery, 14000 Caen, France. Electronic address: romain.paillot@aht.org.uk.
MeSH Terms
- Animals
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses
- Influenza A Virus, H3N8 Subtype / immunology
- Influenza A Virus, H3N8 Subtype / pathogenicity
- Orthomyxoviridae Infections / prevention & control
- Orthomyxoviridae Infections / veterinary
- Orthomyxoviridae Infections / virology
- Vaccination / veterinary
- Virus Shedding
Citations
This article has been cited 7 times.- Thieulent CJ, Sutton G, Toquet MP, Fremaux S, Hue E, Fortier C, Pléau A, Deslis A, Abrioux S, Guitton E, Pronost S, Paillot R. Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C(2254) Variant.. Pathogens 2022 May 4;11(5).
- Oladunni FS, Oseni SO, Martinez-Sobrido L, Chambers TM. Equine Influenza Virus and Vaccines.. Viruses 2021 Aug 20;13(8).
- Sutton G, Thieulent C, Fortier C, Hue ES, Marcillaud-Pitel C, Pléau A, Deslis A, Guitton E, Paillot R, Pronost S. Identification of a New Equid Herpesvirus 1 DNA Polymerase (ORF30) Genotype with the Isolation of a C(2254)/H(752) Strain in French Horses Showing no Major Impact on the Strain Behaviour.. Viruses 2020 Oct 13;12(10).
- Fougerolle S, Fortier C, Legrand L, Jourdan M, Marcillaud-Pitel C, Pronost S, Paillot R. Success and Limitation of Equine Influenza Vaccination: The First Incursion in a Decade of a Florida Clade 1 Equine Influenza Virus that Shakes Protection Despite High Vaccine Coverage.. Vaccines (Basel) 2019 Nov 2;7(4).
- Blanco-Lobo P, Rodriguez L, Reedy S, Oladunni FS, Nogales A, Murcia PR, Chambers TM, Martinez-Sobrido L. A Bivalent Live-Attenuated Vaccine for the Prevention of Equine Influenza Virus.. Viruses 2019 Oct 11;11(10).
- Singh RK, Dhama K, Karthik K, Khandia R, Munjal A, Khurana SK, Chakraborty S, Malik YS, Virmani N, Singh R, Tripathi BN, Munir M, van der Kolk JH. A Comprehensive Review on Equine Influenza Virus: Etiology, Epidemiology, Pathobiology, Advances in Developing Diagnostics, Vaccines, and Control Strategies.. Front Microbiol 2018;9:1941.
- Paillot R, Garrett D, Lopez-Alvarez MR, Birand I, Montesso F, Horspool L. The Immunity Gap Challenge: Protection against a Recent Florida Clade 2 Equine Influenza Strain.. Vaccines (Basel) 2018 Jul 2;6(3).
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