title: Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease.
abstract: Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (ΔgD(-/+gD-1)). Subcutaneous immunization of C57BL/6 or BALB/c mice with ΔgD(-/+gD1) provided 100% protection against lethal intravaginal or skin challenges and prevented latency. ΔgD(-/+gD1) elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fcγ-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Petro
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: González
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cheshenko
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jandl
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, New York, United States.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Khajoueinejad
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Angèle
authors.initials: A
authors.lastname: Bénard
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Mayami
authors.initials: M
authors.lastname: Sengupta
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000517:prevention & control*; D017193:Skin Diseases, Viral / Q000517:prevention & control*; D014623:Vaginal Diseases / Q000517:prevention & control*; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D057134:Antibodies, Neutralizing; D006023:Glycoproteins; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: HSV-2; antibody; immunity; infectious disease; microbiology; mouse; vaccine; virology