title: SR-2P vaginal microbicide gel provides protection against herpes simplex virus 2 when administered as a combined prophylactic and postexposure therapeutic.
abstract: Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR-2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice.
authors.affiliation: Immunology and Infectious Disease, Biosciences Division, SRI International, Menlo Park, California, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fields
authors.affiliation: Pharmaceutical and Chemical Technologies, Biosciences Division, SRI International, Menlo Park, California, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatia
authors.affiliation: Immunology and Infectious Disease, Biosciences Division, SRI International, Menlo Park, California, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Fong
authors.affiliation: Pharmaceutical and Chemical Technologies, Biosciences Division, SRI International, Menlo Park, California, USA.
authors.forename: Mingtao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Pharmaceutical and Chemical Technologies, Biosciences Division, SRI International, Menlo Park, California, USA gita.shankar@sri.com.
authors.forename: Gita N
authors.initials: GN
authors.lastname: Shankar
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D005260:Female; D006561:Herpes Simplex / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000187:drug effects* / Q000472:pathogenicity*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D014622:Vaginal Creams, Foams, and Jellies