A vaccine targeting ovine herpesvirus 2 glycoprotein B protects against sheep-associated malignant catarrhal fever

Authors: Cunha, Cristina; Baker, Katherine; O'TOOLE, DONAL - University Of Wyoming; COLE, EMILY - Washington State University; SHRINGI, SMRITI - Washington State University; DEWALS, BENJAMIN - University Of Liege; VANDERPLASSCHEN, ALAIN - University Of Liege; LI, HONG - Retired ARS Employee

Submitted to: Vaccines
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2022
Publication Date: 12/15/2022
Citation: Cunha, C.W., Baker, K.N., O'Toole, D., Cole, E., Shringi, S., Dewals, B.G., Vanderplasschen, A., Li, H. 2022. A vaccine targeting ovine herpesvirus 2 glycoprotein B protects against sheep-associated malignant catarrhal fever. Vaccines. 10(12). Article 2156. https://doi.org/10.3390/vaccines10122156.
DOI: https://doi.org/10.3390/vaccines10122156

Interpretive Summary: Sheep associated malignant catarrhal fever (SA-MCF) is a complex and often fatal disease of several animals, including bison, cattle, deer, and pigs. The disease is caused by a virus called ovine herpesvirus 2 (OvHV-2) transmitted by sheep. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate safety, immunogenicity, and protection efficacy of a SA-MCF vaccine candidate. The vaccine consists of a non-pathogenic viral vector that produces an OvHV-2 protein known to induce protective immune responses, glycoprotein B (gB). Rabbits were used in this study as laboratory animal models. For immunizations, the viral vector was delivered alone in three immunizations or following two OvHV-2 gB DNA immunizations. The viral vector was delivered by intravenous or intramuscular inoculations and the DNA by intradermal shots using a gene gun. The vaccine candidate was deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced in all vaccinated rabbits. 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 non-vaccinated controls developed the disease. The significant protection efficacy obtained with the vaccine platforms tested in this study encourages trials in relevant livestock species, such as cattle and bison.

Technical 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.