title: A Vaxfectin(®)-adjuvanted HSV-2 plasmid DNA vaccine is effective for prophylactic and therapeutic use in the guinea pig model of genital herpes.
abstract: Here we describe studies in the guinea pig model of genital herpes to evaluate a novel plasmid DNA (pDNA) vaccine encoding the HSV-2 glycoprotein D and UL46 and UL47 genes encoding tegument proteins VP11/12 and VP 13/14 (gD2/UL46/UL47), formulated with a cationic lipid-based adjuvant Vaxfectin(®). Prophylactic immunization with Vaxfectin(®)-gD2/UL46/UL47 significantly reduced viral replication in the genital tract, provided complete protection against both primary and recurrent genital skin disease following intravaginal HSV-2 challenge, and significantly reduced latent HSV-2 DNA in the dorsal root ganglia compared to controls. We also examined the impact of therapeutic immunization of HSV-2 infected animals. Here, Vaxfectin(®)-gD2/UL46/UL47 immunization significantly reduced both the frequency of recurrent disease and viral shedding into the genital tract compared to controls. This novel adjuvanted pDNA vaccine has demonstrated both prophylactic and therapeutic efficacy in the guinea pig model of genital herpes and warrants further development.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-0436, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Veselenak
authors.forename: Mark
authors.initials: M
authors.lastname: Shlapobersky
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pyles
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
authors.forename: Sean M
authors.initials: SM
authors.lastname: Sullivan
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000821:virology; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D010957:Plasmids; D012867:Skin / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D022283:Herpesvirus Vaccines; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040570:glycoprotein D-herpes simplex virus type 2; C460866:vaxfectin