title: Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection.
abstract: The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD(50) inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine.
authors.affiliation: Vical Incorporated, 10390 Pacific Center Ct, San Diego, CA 92121, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Shlapobersky
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Marshak
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Vical Incorporated, 10390 Pacific Center Ct, San Diego, CA 92121, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Vical Incorporated, 10390 Pacific Center Ct, San Diego, CA 92121, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Chu
authors.affiliation: Vical Incorporated, 10390 Pacific Center Ct, San Diego, CA 92121, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Rolland
authors.affiliation: Vical Incorporated, 10390 Pacific Center Ct, San Diego, CA 92121, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Sullivan
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98195, USA.|Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.|Benaroya Research Institute, Seattle, WA 98101, USA.|Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C460866:vaxfectin