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An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation.
Abstract: Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day -55 and -27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day -70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research.
Publication Date: 2022-06-27 PubMed ID: 35891381PubMed Central: PMC9318657DOI: 10.3390/v14071401Google 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
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research was conducted to study the potential of horses as model species for Hepacivirus vaccine studies. The study evaluated the host response of these horses to a recombinant protein vaccine for equine hepacivirus (EqHV) and subsequent inoculation with the virus.
Methodology
- The study involved a comparison between four ponies, which were administered with a prime and booster vaccinations, and two control ponies that only received an adjuvant.
- The vaccinations of the primary group comprised recombinant protein and adjuvant, and were administered at two points – day -55 and -27. Following these, all the ponies were inoculated with EqHV RNA-positive plasma on day 0.
- Data was collected over a span of 26 weeks (from day -70 to +112), during which blood samples and liver biopsies were obtained.
Data Analysis
- Serum analysis involved detection of E2-specific and nonstructural protein 3-specific Immunoglobulin G, EqHV RNA, and assessment of haematology, serum biochemistry, and metabolomics.
- The liver tissue analysis comprised of RNA detection and sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization.
Results
- The study did not observe full protective immunity against EqHV even after the vaccination. However, the vaccinated ponies had a quicker clearance of the EqHV RNA from the serum compared to the control ones.
- The vaccinated group also appeared to recover earlier from EqHV-associated liver inflammation, as per the observations from the collected liver tissue samples.
Conclusion
- Although it did not offer full protective immunity, the study promisingly showed quicker recovery in vaccinated ponies. Thus, the researchers suggested that horses could serve as a potential surrogate model for future research on Hepacivirus vaccines.
Cite This Article
APA
Badenhorst M, Saalmu00fcller A, Daly JM, Ertl R, Stadler M, Puff C, de le Roi M, Baumgu00e4rtner W, Engelmann M, Brandner S, Junge HK, Pratscher B, Volz A, Saunier B, Krey T, Wittmann J, Heelemann S, Delarocque J, Wagner B, Todt D, Steinmann E, Cavalleri JV.
(2022).
An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation.
Viruses, 14(7), 1401.
https://doi.org/10.3390/v14071401 Publication
Researcher Affiliations
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK.
- VetCore Facility for Research, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Institute of Pathology, University of Veterinary Medicine Hanover, 30559 Hanover, Germany.
- Institute of Pathology, University of Veterinary Medicine Hanover, 30559 Hanover, Germany.
- Institute of Pathology, University of Veterinary Medicine Hanover, 30559 Hanover, Germany.
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany.
- VetFarm, University of Veterinary Medicine Vienna (Vetmeduni), Kremesberg 13, 2563 Pottenstein, Austria.
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Clinic for Equine Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Clinical Unit of Small Animal Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
- Institute of Virology, University of Veterinary Medicine Hanover Foundation, 30559 Hanover, Germany.
- Structural Virology Unit, Institut Pasteur, Paris Citu00e9 University, CNRS UMR 3569, 75015 Paris, France.
- Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of Lu00fcbeck, 23562 Lu00fcbeck, Germany.
- Center for Structural Systems Biology (CSSB), 22607 Hamburg, Germany.
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lu00fcbeck-Borstel-Riems, 23562 Lu00fcbeck, Germany.
- Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, 30625 Hanover, Germany.
- Institute of Virology, Hanover Medical School, 30625 Hanover, Germany.
- Lifespin GmbH, 93053 Regensburg, Germany.
- Lifespin GmbH, 93053 Regensburg, Germany.
- Clinic for Horses, University of Veterinary Medicine Hanover, 30559 Hanover, Germany.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany.
- European Virus Bioinformatics Centre (EVBC), 07743 Jena, Germany.
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany.
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinu00e4rplatz 1, 1210 Vienna, Austria.
MeSH Terms
- Animals
- Antibodies, Viral
- Hepacivirus / genetics
- Horse Diseases / prevention & control
- Horses
- Immunoglobulin G
- In Situ Hybridization, Fluorescence
- Phylogeny
- RNA
- Vaccination / veterinary
- Vaccines, Synthetic / genetics
Grant Funding
- I 4835-B / Austrian Science Fund FWF
Conflict of Interest Statement
The authors declare no conflict of interest.
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