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Article

An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation

by
Marcha Badenhorst
1,
Armin Saalmüller
2,
Janet M. Daly
3,
Reinhard Ertl
4,
Maria Stadler
2,
Christina Puff
5,
Madeleine de le Roi
5,
Wolfgang Baumgärtner
5,
Michael Engelmann
6,
Sabine Brandner
7,
Hannah K. Junge
1,8,
Barbara Pratscher
1,9,
Asisa Volz
10,
Bertrand Saunier
11,
Thomas Krey
12,13,14,15,16,
Johannes Wittmann
17,
Steffen Heelemann
17,
Julien Delarocque
18,
Bettina Wagner
19,
Daniel Todt
6,20,
Eike Steinmann
6,* and
Jessika-M. V. Cavalleri
1,*add Show full author list remove Hide full author list
1
Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinärplatz 1, 1210 Vienna, Austria
2
Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna (Vetmeduni), Veterinärplatz 1, 1210 Vienna, Austria
3
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK
4
VetCore Facility for Research, University of Veterinary Medicine Vienna (Vetmeduni), Veterinärplatz 1, 1210 Vienna, Austria
5
Institute of Pathology, University of Veterinary Medicine Hanover, 30559 Hanover, Germany
6
Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany
7
VetFarm, University of Veterinary Medicine Vienna (Vetmeduni), Kremesberg 13, 2563 Pottenstein, Austria
8
Clinic for Equine Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland
9
Clinical Unit of Small Animal Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna (Vetmeduni), Veterinärplatz 1, 1210 Vienna, Austria
10
Institute of Virology, University of Veterinary Medicine Hanover Foundation, 30559 Hanover, Germany
11
Structural Virology Unit, Institut Pasteur, Paris Cité University, CNRS UMR 3569, 75015 Paris, France
12
Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of Lübeck, 23562 Lübeck, Germany
13
Center for Structural Systems Biology (CSSB), 22607 Hamburg, Germany
14
German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 23562 Lübeck, Germany
15
Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, 30625 Hanover, Germany
16
Institute of Virology, Hanover Medical School, 30625 Hanover, Germany
17
Lifespin GmbH, 93053 Regensburg, Germany
18
Clinic for Horses, University of Veterinary Medicine Hanover, 30559 Hanover, Germany
19
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
20
European Virus Bioinformatics Centre (EVBC), 07743 Jena, Germany
 
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*
Authors to whom correspondence should be addressed.
Viruses 2022, 14(7), 1401; https://doi.org/10.3390/v14071401
Submission received: 6 April 2022 / Revised: 27 May 2022 / Accepted: 15 June 2022 / Published: 27 June 2022
(This article belongs to the Special Issue Viral Diseases of Horses and Humans: Epidemiology, Pathogenesis and Immunity)
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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.
Keywords: horse; liver; RNA sequencing; immunoglobulins; hepacivirus A; vaccine; viral challenge; metabolomics horse; liver; RNA sequencing; immunoglobulins; hepacivirus A; vaccine; viral challenge; metabolomics

Share and Cite

MDPI and ACS Style

Badenhorst, M.; Saalmüller, A.; Daly, J.M.; Ertl, R.; Stadler, M.; Puff, C.; de le Roi, M.; Baumgärtner, W.; Engelmann, M.; Brandner, S.; et al. An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation. Viruses 2022, 14, 1401. https://doi.org/10.3390/v14071401

AMA Style

Badenhorst M, Saalmüller A, Daly JM, Ertl R, Stadler M, Puff C, de le Roi M, Baumgärtner W, Engelmann M, Brandner S, et al. An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation. Viruses. 2022; 14(7):1401. https://doi.org/10.3390/v14071401

Chicago/Turabian Style

Badenhorst, Marcha, Armin Saalmüller, Janet M. Daly, Reinhard Ertl, Maria Stadler, Christina Puff, Madeleine de le Roi, Wolfgang Baumgärtner, Michael Engelmann, Sabine Brandner, and et al. 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, no. 7: 1401. https://doi.org/10.3390/v14071401

APA Style

Badenhorst, M., Saalmüller, A., Daly, J. M., Ertl, R., Stadler, M., Puff, C., de le Roi, M., Baumgärtner, W., Engelmann, M., Brandner, S., Junge, H. K., Pratscher, B., Volz, A., Saunier, B., Krey, T., Wittmann, J., Heelemann, S., Delarocque, J., Wagner, B., ... Cavalleri, J.-M. V. (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

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