title: A single intramuscular vaccination of mice with the HSV-1 VC2 virus with mutations in the glycoprotein K and the membrane protein UL20 confers full protection against lethal intravaginal challenge with virulent HSV-1 and HSV-2 strains.
abstract: Herpes Simplex Virus type-1 (HSV-1) and type-2 (HSV-2) establish life-long infections and cause significant orofacial and genital infections in humans. HSV-1 is the leading cause of infectious blindness in the western world. Currently, there are no available vaccines to protect against herpes simplex infections. Recently, we showed that a single intramuscular immunization with an HSV-1(F) mutant virus lacking expression of the viral glycoprotein K (gK), which prevents the virus from entering into distal axons of ganglionic neurons, conferred significant protection against either virulent HSV-1(McKrae) or HSV-2(G) intravaginal challenge in mice. Specifically, 90% of the mice were protected against HSV-1(McKrae) challenge, while 70% of the mice were protected against HSV-2(G) challenge. We constructed the recombinant virus VC2 that contains specific mutations in gK and the membrane protein UL20 preventing virus entry into axonal compartments of neurons, while allowing efficient replication in cell culture, unlike the gK-null virus, which has a major defect in virus replication and spread. Intramuscular injection of mice with 107 VC2 plaque forming units did not cause any significant clinical disease in mice. A single intramuscular immunization with the VC2 virus protected 100% of mice against lethal intravaginal challenge with either HSV-1(McKrae) or HSV-2(G) viruses. Importantly, vaccination with VC2 produced robust cross protective humoral and cellular immunity that fully protected vaccinated mice against lethal disease. Quantitative PCR did not detect any viral DNA in ganglionic tissues of vaccinated mice, while unvaccinated mice contained high levels of viral DNA. The VC2 virus may serve as an efficient vaccine against both HSV-1 and HSV-2 infections, as well as a safe vector for the production of vaccines against other viral and bacterial pathogens.
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Stanfield
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Jacque
authors.initials: J
authors.lastname: Stahl
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Chouljenko
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subramanian
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Anu-Susan
authors.initials: AS
authors.lastname: Charles
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Saied
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Walker
authors.affiliation: Division of Biotechnology & Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Kousoulas
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006561:Herpes Simplex / Q000401:mortality / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007273:Injections, Intramuscular; D051379:Mice; D009154:Mutation; D014611:Vaccination; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D022301:Herpes Simplex Virus Vaccines; C121742:UL20 protein, Herpes simplex virus type 1; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins