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

Abstract

An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards 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 approaches for vaccine development 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 an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-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 mock-vaccinated 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 an SA-MCF vaccine; however, improvements are needed to increase protection rates.

Bovine Herpesvirus-4 Based Vaccine Provides Protective Immunity against Streptococcus suis Disease in a Rabbit Model

“…BoHV-4 has been identified as a vaccine vector that is able to deliver antigens from different pathogens in multiple divergent animal species, including rabbits [ 22 , 23 ] and pigs [ 24 , 25 ]. Given the relative high cost as well as ethical concerns of testing a new prototype vaccine in pigs, a rabbit S. suis immunogenicity/challenge model was used in this study for the initial evaluation of immune response and protection efficacy of BoHV-4/GMD and BoHV-4/SLY against S. suis infection.…”

“…Two-month-old New Zealand rabbits were purchased from Shanghai JieSiJie Laboratory Animal Co., Ltd. Shanghai, China, and confirmed as negative for S. suis antibodies using an enzyme-linked immunosorbent assay (ELISA). Previously, antibody responses induced by BoHV-4 based vaccine vectors have been evaluated in multiple animal species via different routes of administration, including intramuscular (IM) [ 25 ]; intravenous (IV) [ 23 ]; intraperitoneal (IP) [ 21 ]; and intranasal (IN) [ 29 ]. To test the antibody response following vaccination with different routes, nine rabbits were divided into three groups of three rabbits each and vaccinated with BoHV-4/GMD, BoHV-4/SLY, and BoHV-4 WT at a dose of 1.52 × 10 9 TCID50 via intramuscular (IM), subcutaneous (SC), or intranasal (IN) routes, as indicated.…”

“…Consistent with wide host tropism, BoHV-4 is capable of replicating in vitro in cells from a variety of animal species [ 21 ]. BoHV-4 has also been shown to be able to experimentally infect a variety of animal species in addition to ruminants, including rabbits [ 22 , 23 ] and pigs [ 24 , 25 ]. BoHV-4 has been shown to be highly immunogenic in these species.…”

“…BoHV-4 has been shown to be highly immunogenic in these species. This high immunogenicity, combined with the lack of pathogenicity and capacity for accommodating large amounts of foreign genetic material [ 23 ], has resulted in considering BoHV-4 as a promising vaccine vector. To date, BoHV-4 vectors have been used to deliver a variety of heterologous antigens from different pathogens in several animal models [ 21 , 23 , 25 , 26 , 27 , 28 , 29 ].…”

Immunization With Bovine Herpesvirus-4-Based Vector Delivering PPRV-H Protein Protects Sheep From PPRV Challenge

“…Although an ovine herpesvirus-2 glycoprotein ( 25 ) and a bovine viral diarrhea virus glycoprotein E2 ( 14 ) have already been expressed using the BoHV-4-A-ΔTK vector and delivered in sheep, we successfully describe in this work, for the first time, the efficacy of BoHV-4-based vector in terms of vaccination in sheep. Because PPRV mainly replicates in the respiratory tract, an interesting approach to analyze in future vaccination trials against PPRV would be the intranasal antigen delivery, which has already been used successfully with the BoHV-4 vector in cattle ( 26 ).…”