title: Seminal plasma reduces the effectiveness of topical polyanionic microbicides.
abstract: The objective of this study was to test the activity of microbicides against herpes simplex virus type 2 (HSV-2) introduced in seminal plasma. We found that seminal plasma interfered with the activity of PRO 2000 and of cellulose sulfate, increasing by 100-fold the concentration of drug required to inhibit 90% of viral plaque formation. Seminal plasma competitively inhibited binding of the microbicides to the HSV-2 envelope. Most of the interference was found in a high molecular-weight fraction; tandem mass spectrometry identified the proteins as fibronectin-1 and lactoferrin. In a murine model, the interference translated in vivo into a loss in protection. We found that 2% PRO 2000 gel protected 100% of mice challenged intravaginally with HSV-2 introduced in PBS, whereas only 55% of mice were protected if virus was introduced in seminal plasma (P=.0007, log rank test). If these findings are reflective of what occurs in humans, modifications to microbicides to ensure that they retain activity in the presence of seminal plasma are indicated.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Sarju
authors.initials: S
authors.lastname: Patel
authors.forename: Ehsan
authors.initials: E
authors.lastname: Hazrati
authors.forename: Natalia
authors.initials: N
authors.lastname: Cheshenko
authors.forename: Benjamin
authors.initials: B
authors.lastname: Galen
authors.forename: Heyi
authors.initials: H
authors.lastname: Yang
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Guzman
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Keller
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009282:Naphthalenesulfonates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012661:Semen / Q000737:chemistry*
chemical_list: D000891:Anti-Infective Agents, Local; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers