title: Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.
abstract: Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHVXP1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals (P< 0.01 orP< 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P< 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P< 0.01 orP< 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4+T cells and CD8+T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals.IMPORTANCEA novel virus-vectored VC2-EHV-1-gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Shiliang A
authors.initials: SA
authors.lastname: Liu
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Stanfield
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Chouljenko
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Naidu
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Langohr
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Piero
authors.affiliation: Department of Clinical Studies and Pathology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ferracone
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Alma A
authors.initials: AA
authors.lastname: Roy
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA vtgusk@lsu.edu.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Kousoulas
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006734:Horse Diseases / Q000517:prevention & control* / Q000821:virology; D006736:Horses; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007273:Injections, Intramuscular; D051379:Mice; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C488988:glycoprotein D, Equid herpesvirus 1
keywords: EHV-1; HSV-1; equine herpesvirus; glycoprotein D; immune response; live vector vaccines; mouse model