title: Single dose of glycoprotein K (gK)-deleted HSV-1 live-attenuated virus protects mice against lethal vaginal challenge with HSV-1 and HSV-2 and induces lasting T cell memory immune responses.
abstract: BACKGROUND
  Herpes simplex virus type-1(HSV-1) and HSV-2 are important human pathogens that cause significant ocular and urogenital complications, respectively. We have previously shown that HSV-1 virions lacking glycoprotein K (gK) are unable to enter into neurons via synaptic axonal membranes and be transported in either retrograde or anterograde manner. Here, we tested the ability of HSV-1 (F) gK-null to protect against lethal challenge with either highly virulent ocular HSV-1 (McKrae strain), or genital HSV-2 (G strain). The gK-null virus vaccine efficiently protected mice against lethal vaginal infection with either HSV-1(McKrae) or HSV-2 (G).
  
  
  RESULTS
  Female mice were immunized via a single intramuscular injection with 106 PFU of the gK-null virus. Immunized mice were treated with Depo-Provera fourteen days after vaccination and were challenged via the vaginal route one week later. Ninety percent of mice vaccinated with the gK-null virus survived HSV-1 (McKrae) challenge, while 70% of these mice survived after HSV-2 (G) challenge. Moreover, all vaccinated mice exhibited substantially reduced disease symptoms irrespective of HSV-1 or HSV-2 challenge as compared to the mock vaccinated challenge group. T-cell memory immune responses to specific glycoprotein B (gB) and glycoprotein D (gD) peptide epitopes were detectable at 7 months post vaccination.
  
  
  CONCLUSIONS
  These results suggest that the highly attenuated, non-neurotropic gK-null virus may be used as an effective vaccine to protect against both virulent HSV-1 and HSV-2 genital infections and induce lasting immune responses.
authors.forename: Arun V
authors.initials: AV
authors.lastname: Iyer
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Chouljenko
authors.forename: Jason D
authors.initials: JD
authors.lastname: Walker
authors.forename: Brent
authors.initials: B
authors.lastname: Stanfield
authors.affiliation: Division of Biotechnology and Molecular Medicine, and Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, LA 70803, USA. vtgusk@lsu.edu.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Kousoulas
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006558:Herpes Genitalis / Q000517:prevention & control*; D006561:Herpes Simplex / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D022283:Herpesvirus Vaccines; C072448:UL53 protein, Human herpesvirus 1; D014613:Vaccines, Attenuated; D014764:Viral Proteins