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.