title: Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.
abstract: Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Diaz
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States. Electronic address: david_knipe@hms.harvard.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D000069078:Seroconversion; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D017735:Virus Latency
chemical_list: D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins; C047419:herpes simplex virus type-2 protein ICP8
keywords: animal infection model; genital disease; herpes simplex virus; latent infection; seroconversion; vaccines