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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, Toole Donal, Cole Emily, Baker Katherine N., White Stephen N., Donofrio Gaetano, Li Hong, Cunha Cristina Wetzel
Vaccines 2021 v.9 no. pp. 2
Bovine gammaherpesvirus 4, Ovine gammaherpesvirus 2, animal disease models, genetic engineering, glycoproteins, humoral immunity, immunogenicity, intranasal administration, lethal dose, live vaccines, malignant catarrhal fever, neutralizing antibodies, rabbits, vaccination, vaccine development, vector vaccines, viral antigens, viral vaccines
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.