title: Topical SMIP-7.7, a toll-like receptor 7 agonist, protects against genital herpes simplex virus type-2 disease in the guinea pig model of genital herpes.
abstract: BACKGROUND
  Development of more effective therapies for genital herpes simplex virus type-2 (HSV-2) infections remains a priority. The toll-like receptors (TLR) are attractive targets for the immunomodulation of primary and recurrent genital herpes infection. The guinea pig model of genital HSV-2 disease was therefore used to evaluate the efficacy of a new TLR-7 agonist, SMIP-7.7.
  
  
  METHODS
  The effects of SMIP-7.7 at concentrations between 0.90% and 0.09% were compared to the vehicle control or Aldara(®) (3M Health Care Limited, Northridge, CA, USA) as treatment for genital HSV-2 infections. Following intravaginal inoculation of Hartley guinea pigs with 10(6) pfu HSV-2 (MS strain), animals were treated intravaginally beginning at 36 h post-infection. Animals were evaluated for acute disease, acute virus replication, recurrent disease and shedding, as well as infection of the dorsal root ganglia.
  
  
  RESULTS
  Treatment with SMIP-7.7 significantly decreased mean total lesion scores during primary infection (all doses, P<0.01 compared with vehicle control, and similar to Aldara(®)). Vaginal virus titres were reduced in treated animals compared with vehicle control (P<0.001 for each treatment versus vehicle control on day 4). Treatment with SMIP-7.7 also significantly decreased the number of recurrent lesion days, the number of days with recurrent virus shedding and the infection of the dorsal root ganglia compared to the vehicle control, and was similar to Aldara(®). As opposed to Aldara(®), SMIP-7.7 did not induce fever or weight loss during treatment.
  
  
  CONCLUSIONS
  SMIP-7.7 improves the outcome of primary and recurrent HSV-2 disease comparable to Aldara(®) but without some of the side effects associated with Aldara(®).
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. david.bernstein@cchmc.org.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Cardin
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Bravo
authors.forename: Julie
authors.initials: J
authors.lastname: Earwood
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Clark
authors.forename: Yongkai
authors.initials: Y
authors.lastname: Li
authors.forename: Pranab
authors.initials: P
authors.lastname: Mishra
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: Nayak
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Miller
authors.forename: Tom Y-H
authors.initials: TY
authors.lastname: Wu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cooke
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Valiante
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000302:isolation & purification; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D051199:Toll-Like Receptor 7