TY - JOUR
T1 - An Equine Model for Vaccination against a Hepacivirus
T2 - Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation
AU - Badenhorst, Marcha
AU - Saalmüller, Armin
AU - Daly, Janet M.
AU - Ertl, Reinhard
AU - Stadler, Maria
AU - Puff, Christina
AU - de le Roi, Madeleine
AU - Baumgärtner, Wolfgang
AU - Engelmann, Michael
AU - Brandner, Sabine
AU - Junge, Hannah K.
AU - Pratscher, Barbara
AU - Volz, Asisa
AU - Saunier, Bertrand
AU - Krey, Thomas
AU - Wittmann, Johannes
AU - Heelemann, Steffen
AU - Delarocque, Julien
AU - Wagner, Bettina
AU - Todt, Daniel
AU - Steinmann, Eike
AU - Cavalleri, Jessika M.V.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133335598&partnerID=8YFLogxK
U2 - 10.3390/v14071401
DO - 10.3390/v14071401
M3 - Journal articles
C2 - 35891381
AN - SCOPUS:85133335598
SN - 1999-4915
VL - 14
JO - Viruses
JF - Viruses
IS - 7
M1 - 1401
ER -