title: A novel HSV-2 subunit vaccine induces GLA-dependent CD4 and CD8 T cell responses and protective immunity in mice and guinea pigs.
abstract: OBJECTIVE
  There is currently no licensed prophylactic or therapeutic vaccine for HSV-2 infection.
  
  
  METHODS
  We developed a novel preclinical vaccine candidate, G103, consisting of three recombinantly expressed HSV-2 proteins (gD and the UL19 and UL25 gene products) adjuvanted with the potent synthetic TLR4 agonist glucopyranosyl lipid A (GLA) formulated in stable emulsion. The vaccine was tested for immunogenicity and efficacy in pre-clinical models for preventative and therapeutic vaccination.
  
  
  RESULTS
  Vaccination of mice with G103 elicited antigen-specific binding and neutralizing antibody responses, as well as robust CD4 and CD8 effector and memory T cells. The T cell responses were further boosted by subsequent challenge with live virus. Prophylactic immunization completely protected against lethal intravaginal HSV-2 infection in mice, with only transient replication of virus in the genital mucosa and sterilizing immunity in dorsal root ganglia. Supporting the use of G103 therapeutically, the vaccine expanded both CD4 and CD8 T cells induced in mice by previous infection with HSV-2. In the guinea pig model of recurrent HSV-2 infection, therapeutic immunization with G103 was approximately 50% effective in reducing the number of lesions per animal as well as the overall lesions score.
  
  
  CONCLUSIONS
  Taken together, the data show that G103 is a viable candidate for development of a novel prophylactic and therapeutic HSV-2 vaccine.
authors.affiliation: Immune Design, Seattle, WA 98102, United States.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Odegard
authors.affiliation: Immune Design, Seattle, WA 98102, United States.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flynn
authors.affiliation: Immune Design, Seattle, WA 98102, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Campbell
authors.affiliation: Immune Design, Seattle, WA 98102, United States.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robbins
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Kening
authors.initials: K
authors.lastname: Wang
authors.affiliation: Immune Design, Seattle, WA 98102, United States. Electronic address: jan.termeulen@immunedesign.com.
authors.forename: Jan
authors.initials: J
authors.lastname: Ter Meulen
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, United States; Benaroya Research Institute, Seattle, WA 98101, United States; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, United States; Department of Global Health, University of Washington, Seattle, WA 98195, United States; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000008:administration & dosage*; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D007156:Immunologic Memory; D008050:Lipid A / Q000008:administration & dosage*; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D005960:Glucosides; D022283:Herpesvirus Vaccines; D008050:Lipid A; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C000608161:glucopyranosyl lipid-A
keywords: CD4 T cells; CD8 T cells; GLA adjuvant; HSV-2 vaccine