Clinical protection of goats against CpHV-1 induced genital disease with a BoHV-4-based vector expressing CpHV-1 gD

PLoS One. 2013;8(1):e52758. doi: 10.1371/journal.pone.0052758. Epub 2013 Jan 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cytomegalovirus / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genital Diseases, Female / prevention & control
  • Genital Diseases, Female / veterinary*
  • Genital Diseases, Female / virology
  • Glycoproteins / metabolism
  • Goat Diseases / prevention & control
  • Goat Diseases / virology*
  • Goats
  • HEK293 Cells
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / veterinary*
  • Herpesvirus 4, Bovine / metabolism*
  • Humans
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptides / chemistry
  • Recombinant Proteins / metabolism
  • Varicellovirus / immunology*
  • Viral Vaccines / therapeutic use*
  • Virus Shedding

Substances

  • Glycoproteins
  • Peptides
  • Recombinant Proteins
  • Viral Vaccines

Grants and funding

This work was supported by grants from the Ministry of Education, University and Research (PRIN 2008, project 2008WCSTJM “Activity of antiviral drugs and vaccines against herpesvirus infection in goats: an animal model for the study of genital herpesvirus infection in man”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.