title: Preventive effect of local plasmid DNA vaccine encoding gD or gD-IL-2 on herpetic keratitis.
abstract: OBJECTIVE
  The goal of this study was to evaluate the effectiveness of a local plasmid DNA vaccine encoding herpes simplex virus (HSV) type 1 glycoprotein D (gD) or gD-interleukin (IL)-2 (chimeric gene of gD and human IL-2) in preventing murine herpetic keratitis.
  
  
  METHODS
  Plasmids containing gD (pHSDneo1), gD-IL-2 (pHDLneo1), or vaccine vector (pHSGneo) were injected subconjunctivally with BALB/c mice on days 0 and 7 (90 microgram x 2). Immunization was indicated by positive virus-neutralizing antibody titer, swollen pinna (due to delayed-type hypersensitivity [DTH] reaction), and release of (51)Cr from splenic and/or local cytotoxic effector cells on day 28. In another group of the immunized mice, corneas were challenged with HSV-1 (CHR3 strain, 10 microliter of 3 x 10(6) plaque-forming units [PFU]/ml). Mice were evaluated for clinical signs of epithelial or stromal keratitis on days 1 through 8 and days 10 and 14 or measured on days 2, 4, or 6 for viral titers in the eyes, trigeminal ganglia, and brain.
  
  
  RESULTS
  All gD-DNA-injected mice obtained specific immunity. Furthermore, gD-IL-2-DNA elicited a higher DTH reaction and more vigorous cytotoxic effector cell activity. Stromal keratitis scores were lower for all immunized mice compared with control mice, although the difference in epithelial keratitis scores was not statistically significant. Viral titers in eyes, trigeminal ganglia, and brains were suppressed in all immunized mice.
  
  
  CONCLUSIONS
  Local immunization with plasmid DNA encoding gD or gD-IL-2 induces humoral and cellular immunity against HSV-1 and inhibits development of stromal keratitis. gD-IL-2 DNA induces greater cell-mediated immunity than gD DNA alone. A plasmid encoding gD-IL-2 is therefore a promising candidate for a vaccine against HSV-1.
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. tinoue@virus.kyoto-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Y
authors.initials: Y
authors.lastname: Tano
authors.forename: Y
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: A
authors.initials: A
authors.lastname: Aono
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001921:Brain / Q000821:virology; D003319:Corneal Stroma / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000302:isolation & purification; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D012668:Trigeminal Ganglion / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007376:Interleukin-2; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1