title: Clinical protection of goats against CpHV-1 induced genital disease with a BoHV-4-based vector expressing CpHV-1 gD.
abstract: Caprine herpesvirus type 1 (CpHV-1) is an alphaherpesvirus causing genital disease leading to abortion in adult pregnant goats and a systemic disease with high morbility and mortality in kids. Further, Caprine herpesvirus 1 infection represents a valuable large animal model for human herpesvirus induced genital disease, exploitable for pathogenic studies, new vaccines and antiviral molecules testing. Here, the bovine herpesvirus 4 (BoHV-4) based vector derived from an apathogenic isolate of BoHV-4 and expressing the immunodominant CpHV-1 glycoprotein D (BoHV-4-A-gD(cp)gD(106)ΔTK) was constructed and its ability to protect goats against CpHV-1 induced genital disease evaluated. The subcutaneous route of recombinant BoHV-4 administration was first tested in vivo/ex vivo by in vivo image analysis and in vitro by goat skin primary cultures preparation and transduction. Next, an exploratory immunization and safety study in goats was performed with two recombinant BoHV4, BoHV-4-A-gD(cp)gD(106)ΔTK or BoHV-4-CMV-IgK-gE2gD-TM. In both cases no clinical signs were evident but a good titer of serum neutralizing antibodies was produced in all inoculated animals. When a challenge experiment was performed in a new group of animals using a highly pathogenic dose of CpHV-1, all the vaccinated goats with BoHV-4-A-gD(cp)gD(106)ΔTK were protected toward CpHV-1 induced genital disease respect to the unvaccinated control which showed typical vaginal lesions with a high grade of clinical score as well as a long lasting viral shedding. In summary, the data acquired in the present study validate BoHV-4-based vector as a safe and effective viral vector for goat vaccination against CpHV-1 induced genital disease and pave the way for further applications.
authors.affiliation: Department of Medical-Veterinary Science, University of Parma, Parma, Italy. gaetano.donofrio@unipr.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
authors.forename: Valentina
authors.initials: V
authors.lastname: Franceschi
authors.forename: Angela
authors.initials: A
authors.lastname: Lovero
authors.forename: Antonio
authors.initials: A
authors.lastname: Capocefalo
authors.forename: Michele
authors.initials: M
authors.lastname: Camero
authors.forename: Michele
authors.initials: M
authors.lastname: Losurdo
authors.forename: Sandro
authors.initials: S
authors.lastname: Cavirani
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Marinaro
authors.forename: Erika
authors.initials: E
authors.lastname: Grandolfo
authors.forename: Canio
authors.initials: C
authors.lastname: Buonavoglia
authors.forename: Maria
authors.initials: M
authors.lastname: Tempesta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003587:Cytomegalovirus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005831:Genital Diseases, Female / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D006023:Glycoproteins / Q000378:metabolism; D015511:Goat Diseases / Q000517:prevention & control / Q000821:virology*; D006041:Goats; D057809:HEK293 Cells; D006566:Herpesviridae Infections / Q000517:prevention & control / Q000662:veterinary*; D026021:Herpesvirus 4, Bovine / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D018140:Varicellovirus / Q000276:immunology*; D014765:Viral Vaccines / Q000627:therapeutic use*; D017201:Virus Shedding
chemical_list: D006023:Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D014765:Viral Vaccines