A recombinant bovine herpesvirus-4 vectored vaccine delivered via intranasal nebulization elicits viral neutralizing antibody titers in cattle

Abstract

Recombinant herpesvirus vaccine vectors offer distinct advantages in next-generation vaccine development, primarily due to the ability to establish persistent infections to provide sustainable antigen responses in the host. Recombinant bovine herpesvirus-4 (BoHV-4) has been previously shown to elicit protective immunity in model laboratory animal species against a variety of pathogens. For the first time, we describe the induction of antigen-specific immune responses to two delivered antigens in the host species after intranasal nebulization of recombinant BoHV-4 expressing the chimeric peptide containing the bovine viral diarrhea virus (BVDV) glycoprotein E2 and the bovine herpesvirus 1 (BoHV-1) glycoprotein D (BoHV-4-A-CMV-IgK-gE2gD-TM). In this study, four cattle were immunized via intranasal nebulization with the recombinant BoHV-4 construct. Two of the cattle were previously infected with wild-type BoHV-4, and both developed detectable serologic responses to BVDV and BoHV-1. All four immunized cattle developed detectable viral neutralizing antibody responses to BVDV, and one steer developed a transient viral neutralizing response to BoHV-1. Approximately one year after immunization, immunosuppressive doses of the glucocorticoid dexamethasone were administered intravenously to all four cattle. Within two weeks of immunosuppression, all animals developed viral neutralizing antibody responses to BoHV-1, and all animals maintained BVDV viral neutralizing capacity. Overall, nebulization of BoHV-4-A-CMV-IgK-gE2gD-TM persistently infects cattle, is capable of eliciting antigen-specific immunity following immunization, including in the presence of pre-existing BoHV-4 immunity, and recrudescence of the virus boosts the immune response to BoHV-4-vectored antigens. These results indicate that BoHV-4 is a viable and attractive vaccine delivery platform for use in cattle.

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

“…If the recombinant virus did establish latency in the immunized rabbits based on the sustained immune response to BoHV-4, a plausible explanation for the lack of detection of BoHV-4 DNA in blood or tissues is that viral load in the samples tested was below the assay threshold. Similar results were obtained in another study where a recombinant BoHV-4, expressing selected BVDV and BoHV-1 proteins encoded by genes inserted in the BoHV-4 TK locus, was tested in cattle [ 9 ]. In that study, BoHV-4 DNA was not detected in tissues and attempts to recover virus in cell culture were unsuccessful.…”

“…Vector vaccine technology is an attractive way to deliver antigens that has been used successfully in veterinary vaccine development [ 7 ]. Bovine herpesvirus-4 (BoHV-4) has been identified as a reliable vaccine delivery vector [ 8 , 9 , 10 ]. The characteristics of BoHV-4 that favor its use as a vaccine vector include its capability of infecting a variety of hosts with low or no pathogenicity and accommodating large amounts of foreign genetic material.…”

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 ).…”

Evaluation of the Mucosal Immunity Effect of Bovine Viral Diarrhea Virus Subunit Vaccine E2Fc and E2Ft

“…Meanwhile, multivalent E2 subunit vaccines targeting major circulating strains of BVDV can provide partial protection against homologous strains. A recombinant herpesvirus vaccine constructed with BVDV E2 protein and bovine herpesvirus 1 (BoHV-1) D protein induced specific immune responses to both viruses in the host after intranasal nebulization [ 10 ]. Therefore, it might be a good strategy to control BVDV by employing the immunodominant BVDV E2 protein as a subunit vaccine.…”