title: Glycoprotein G of herpes simplex virus 2 as a novel vaccine antigen for immunity to genital and neurological disease.
abstract: The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4(+) T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.
authors.affiliation: Department of Virology, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Görander
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
authors.forename: Madelene
authors.initials: M
authors.lastname: Lindqvist
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Liljeqvist
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D018899:CpG Islands; D006224:Cricetinae; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000276:immunology* / Q000821:virology; D013116:Spinal Cord / Q000821:virology; D014621:Vagina / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D022301:Herpes Simplex Virus Vaccines; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C045464:glycoprotein G, herpes simplex virus type 2; D007371:Interferon-gamma