Location: Animal Disease ResearchTitle: OvHV-2 glycoprotein B delivered by a recombinant BoHV-4 is immunogenic and induces partial protection against sheep-associated malignant catarrhal fever in a rabbit model
|SHRINGI, SMRITI - Washington State University|
|O'TOOLE, DONAL - University Of Wyoming|
|COLE, EMILY - Washington State University|
|BAKER, KATHERINE - Washington State University|
|DONOFRIO, GAETANO - University Of Parma|
|LI, HONG - Retired ARS Employee|
Submitted to: Vaccines
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/22/2021
Publication Date: 1/26/2021
Publication URL: https://handle.nal.usda.gov/10113/7261467
Citation: Shringi, S., O'Toole, D., Cole, E., Baker, K.N., White, S.N., Donofrio, G., Li, H., Cunha, C.W. 2021. OvHV-2 glycoprotein B delivered by a recombinant BoHV-4 is immunogenic and induces partial protection against sheep-associated malignant catarrhal fever in a rabbit model. Vaccines. 9(2). Article 90. https://doi.org/10.3390/vaccines9020090.
Interpretive Summary: Sheep-associated malignant catarrhal fever (SA-MCF) is an often-fatal disease of certain ruminants, including cattle and bison. SA-MCF is caused by ovine herpesvirus-2 (OvHV-2), which is transmitted by sheep. Since there is no treatment for SA-MCF, a vaccine to protect animals from disease is a priority for the livestock industry. Technical difficulties associated with the lack of laboratory systems to attenuate OvHV-2, have delayed vaccine development. In this study, we used a non-pathogenic virus, bovine herpesvirus-4 (BoHV-4), as a vector to deliver an OvHV-2 antigen, glycoprotein gB. Following construction of the recombinant virus and its characterization in vitro, the new virus was used for a vaccine trial in a rabbit model. All rabbits immunized with the BoHV-4-vectored vaccine delivering OvHV-2 gB developed antibody responses, and 42.9 % of them were protected from SA-MCF following challenge with a lethal dose of OvHV-2. These are promising results towards the development of a SA-MCF vaccine, although improvements are needed to increase vaccine efficacy.
Technical Abstract: An efficacious vaccine to sheep-associated malignant catarrhal fever (SA-MCF) is a priority for the livestock industry. Research in SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine-strain. Alternative vaccination approaches are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as a SA-MCF vaccine using a rabbit model. Construction of a viable recombinant virus (BoHV-4-1'TK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. Immunization of rabbits with BoHV-4-1'TK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9 % of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the control group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards a SA-MCF vaccine; however, improvements are still needed to increase protection rates.