Promising findings in a just-published study involving the equine hepacivirus help show the way for further hepatitis vaccine research.
Equine hepacivirus, which affects the liver of horses, is the closest known genetic relative of hepatitis C virus in humans. An effective vaccine is currently not available for either hepacivirus.
Equine hepacivirus, also known as canine hepacivirus, nonprimate hepacivirus and, most recently, Hepacivirus A, not only shares common features of genomic structure with the hepatitis C virus, but also biological properties.
Similar to hepatitis C virus, experimental blood-borne transmission of equine hepacivirus has been shown, both chronic and acute courses of infection have been identified, and its affinity to the liver has been established. Indeed, replication of equine hepacivirus occurs exclusively in the liver.
Marcha Badenhorst and her fellow researchers, writing in the journal Viruses, said several challenges have hindered the development of a vaccine against hepatitis C virus.
These include divergence in the virus, difficulties with culture systems, limited models for testing vaccines, and an incomplete understanding of protective immune responses.
Besides humans, chimpanzees are the only other species naturally susceptible to hepatitis C. A robust animal model is therefore lacking, hampering research into how the disease develops, immune control, and vaccine development.
Equine hepacivirus infection in horses provides a chance to study the virus in a mammal host and assess the induction of a protective immune response.
Six healthy, adult Shetland ponies, comprising three geldings and three mares, aged 8 to 12, were used in the study. Serum analysis showed that all of them were clear of equine hepacivirus.
Four of the ponies received an equine hepacivirus E2 recombinant protein vaccine with an adjuvant, followed by a booster four weeks later. Two ponies, who served as controls, received only adjuvant injections.
All were then infected with the virus. Blood samples and liver biopsies were collected over 26 weeks to determine how the ponies handled the infection.
“Although vaccination did not result in complete protective immunity against experimental equine hepacivirus inoculation, the majority of vaccinated ponies cleared the serum equine hepacivirus RNA earlier than the control ponies,” the study team reported.
“The majority of vaccinated ponies appeared to recover from the equine hepacivirus-associated liver insult earlier than the control ponies,” they said.
E2 immunoglobulin responses were detected in all four ponies who received the vaccine.
The authors noted that, in all six ponies, the peak serum equine hepacivirus RNA load and the subsequent decrease in serum RNA corresponded with peak or near-peak Immunoglobulin G1, suggesting it played a role in initiating clearance of the virus.
Its role in infection clearance and the potential role of a vaccine-induced Immunoglobulin G1 response in accelerating EqHV infection clearance warrant further investigation, they said.
The authors said that an equine model shows promise as a surrogate model for future hepacivirus vaccine research.
“Overall,” they said, “the equine hepacivirus E2 recombinant protein candidate vaccine merits further investigation and may prove useful in the development and optimization of new vaccine strategies, eliciting more effective immune responses.”
They said although the small number of ponies in the vaccine and control groups limited statistical interpretation of results, this feasibility study served as a proof of concept.
The number of animals used was considered the minimum number to meaningfully address the study aims and sufficient to demonstrate the proof of concept.
Overall, the findings point to an earlier response to equine hepacivirus virus infection in vaccinated ponies and earlier restoration of liver metabolic processes.
The study team comprised Badenhorst, Armin Saalmüller, Janet Daly, Reinhard Ertl, Maria Stadler, Christina Puff, Madeleine de le Roi, Wolfgang Baumgärtner, Michael Engelmann, Sabine Brandner, Hannah Junge, Barbara Pratscher, Asisa Volz, Bertrand Saunier, Thomas Krey, Johannes Wittmann, Steffen Heelemann, Julien Delarocque, Bettina Wagner, Daniel Todt, Eike Steinmann and Jessika-M. V. Cavalleri, variously affiliated with a range of institutions, including the University of Veterinary Medicine Vienna (Vetmeduni) and the University of Veterinary Medicine Hanover.
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.; Todt, D.; Steinmann, E.; Cavalleri, J.-M.V. 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