A Vaccine Targeting Ovine Herpesvirus 2 Glycoprotein B Protects against Sheep-Associated Malignant Catarrhal Fever

Abstract

Malignant catarrhal fever (MCF) is a complex and often fatal disease of ungulates. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate a sheep-associated MCF (SA-MCF) vaccine candidate targeting ovine herpesvirus 2 (OvHV-2) glycoprotein B (gB). Rabbits were used as a laboratory animal model to test the safety, immunogenicity, and protective efficacy of a chimeric virus consisting of a recombinant, non-pathogenic strain of alcelaphine herpesvirus-1 encoding OvHV-2 ORF8 to express gB (AlHV-1∆ORF73/OvHV-2-ORF8). Viral-vectored immunizations were performed by using the AlHV-1∆ORF73/OvHV-2-ORF8 chimera alone or as a DNA prime (OvHV-2-ORF8)-virus boost regimen. The viral vector was inoculated by intravenous or intramuscular routes and the DNA was delivered by intradermal shots using a gene gun. The vaccine candidates were deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced by all immunogens. At three weeks post-final immunization, all animals were challenged intranasally with a lethal dose of OvHV-2. MCF protection rates ranging from 66.7% to 71.4% were observed in vaccinated rabbits, while all mock-vaccinated animals developed the disease. The significant protective efficacy obtained with the vaccine platforms tested in this study encourages further trials in relevant livestock species, such as cattle and bison.

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant

“…Therefore, it is possible that two animals showing 100% inhibition in plasma diluted at 1:32 indeed have highly different titers of neutralizing antibodies. Overall, antibody responses obtained in this study are in accordance with previous SA-MCF vaccine trials using BoHV-4 or AlHV-1-vectored OvHV-2 gB vaccine candidates tested in the rabbit model, where the presence of anti-OvHV-2-gB antibodies and protection were also not correlated [ 24 , 31 ]. Taken together, these results suggest that other immune factors, including cellular immunity, are critical for protection against SA-MCF.…”

“…Interestingly, the absence of OvHV-2 DNA in the blood and tissues of the two animals that did not develop SA-MCF upon challenge suggests that protection was achieved by preventing OvHV-2 infection rather than by a reduction in viral load. This, along with other studies targeting OvHV-2 gB as a vaccine [ 24 , 31 ], confirms that sterile immunity based on OvHV-2 gB can be achieved by vaccination.…”

Wildebeest-Derived Malignant Catarrhal Fever: A Bovine Peripheral T Cell Lymphoma Caused by Cross-Species Transmission of Alcelaphine Gammaherpesvirus 1

“…The use of the AlHV-1 strain deleted for ORF73 is of great interest because the strain is unable to establish a latent infection and is therefore rapidly controlled and cleared. A recent study demonstrated that the AlHV-1 strain deleted for ORF73, where the coding sequence of gB (ORF8) was replaced by OvHV-2 gB, was able to replicate in vitro and provide protection against an intranasal challenge with OvHV-2 [ 159 , 160 ]. Thus, the recombinant ORF73-deleted AlHV-1 strain represents a very promising tool for future vaccine development in the near future.…”