title: Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes.
abstract: Current methods for sexually transmitted diseases (STD) prophylaxis, which can be disruptive and inconvenient, must be used before each act of sexual intercourse, so a method that provides protection over the course of many acts is desirable. We used a mouse model of vaginally-transmitted herpes simplex virus 2 (HSV-2) infection to test polymeric controlled-release devices for sustained passive immunoprotection. Vaginal disks were prepared by dispersing a monoclonal antibody to HSV-2 (III-174) within a matrix of poly(ethylene-co-vinyl acetate); these disks released 2 to 40 micrograms/day of antibody into buffered water. When disks were placed in the vagina, large amounts of III-174 (5 to 3,000 ng) were recovered from the vaginal fluid over the next 8 days. Mice were vaginally challenged with 10 ID50 of HSV-2 either 3 or 7 days after disk placement; no mice receiving III-174 disks became infected, while 65% of control mice receiving identical disks with nonspecific IgG did. Controlled-release disks with III-174 provided significant protection against HSV-2 infection (p < 0.005). This new technology for long-term STD prophylaxis should increase user compliance, a factor limiting the efficacy of current methods.
authors.affiliation: Department of Chemical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Sherwood
authors.forename: L
authors.initials: L
authors.lastname: Zeitlin
authors.forename: K J
authors.initials: KJ
authors.lastname: Whaley
authors.forename: R A
authors.initials: RA
authors.lastname: Cone
authors.forename: M
authors.initials: M
authors.lastname: Saltzman
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000008:administration & dosage*; D001709:Biotechnology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D008567:Membranes, Artificial