The concept of the topical microbicide is attractive - a safe and effective, female-controlled product destined for intravaginal use and intended to protect women from acquiring sexually transmitted diseases (STDs). With an increasing number of compounds identified as potential microbicides it is important to develop strategies for identifying the most promising candidates. Studies in Projects 1 and 2 and Core B will identify compounds with excellent in vitro antimicrobial activity against important STD pathogens and outstanding safety profiles. In this project we will investigate the efficacy and safety of selected candidate microbicides using well-characterized animal model of genital tract infection.
In specific aim 1 we will use mouse and guinea pig models of herpes simplex virus (HSV) and chlamydial genital tract infection to assess the ability of microbicides to limit cervico-vaginal infection and, in the case of the genital herpes models, prevent disease. Using these models we will also explore whether microbicides can prevent spread of the pathogen to important secondary sites: for HSV, to sensory ganglion neurons; and for chlamydia, to the upper genital tract. These models allow us explore the effectiveness of promising compounds for either pre- or post-coital use.
In specific aim 2 we will use animal models to examine how microbicides efficacy can be affected by the presence of body fluids (e.g. blood or semen). We will explore whether microbicides might reduce STD transmission from infected women to susceptible male partners by determining whether microbicides can reduce the amount of organism present in cervico-vaginal secretions and by developing and using new murine models of STD transmission.
In specific aim 3 we will explore the important safety issue of whether microbicides are immunotoxic. Using standard immunological methods to assess genital tract immunity, we will explore the potential of candidate microbicides to impact innate immune responses known to be important in protecting the female genital tract against infection by sexually transmitted pathogens. These studies will provide important information regarding the in vivo effectiveness of candidate microbicides in protecting female animals against two important STD pathogens. These experiments will also explore the issue of whether microbicides can impact female to male STD transmission and investigate the important question of whether microbicides are immunotoxic to the female genital tract. Collectively, theses studies will characterize the in vivo behavior of microbicides and identify compounds with outstanding efficacy and safety profiles. Overall, this research is expected to yield information that will allow for the rational prioritization of microbicides for further evaluation in clinical trials.

Project Start
2000-09-01
Project End
2000-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
6
Fiscal Year
2000
Total Cost
$199,510
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Anderson, Robert A; Feathergill, Kenneth A; Chany 2nd, Calvin J et al. (2009) Nitric oxide-dependent human acrosomal loss induced by PPCM (SAMMA) and by nitric oxide donors occurs by independent pathways: basis for synthesis of an improved contraceptive microbicide. J Androl 30:168-82
Milligan, Gregg N; Young, Christal G; Meador, Michael G et al. (2005) Effects of candidate vaginally-applied microbicide compounds on innate immune cells. J Reprod Immunol 66:103-16
Rupp, Richard; Rosenthal, Susan L; Stanberry, Lawrence R (2005) Pediatrics and herpes simplex virus vaccines. Semin Pediatr Infect Dis 16:31-7
Bourne, Nigel; Stegall, Rachael; Montano, Raquel et al. (2005) Efficacy and toxicity of zinc salts as candidate topical microbicides against vaginal herpes simplex virus type 2 infection. Antimicrob Agents Chemother 49:1181-3
Keller, Marla J; Tuyama, Ana; Carlucci, Maria Josefina et al. (2005) Topical microbicides for the prevention of genital herpes infection. J Antimicrob Chemother 55:420-3
John, Minnie; Keller, Marla J; Fam, Ehsan H et al. (2005) Cervicovaginal secretions contribute to innate resistance to herpes simplex virus infection. J Infect Dis 192:1731-40
Anderson, Robert A; Feathergill, Kenneth; Diao, Xiao-Hui et al. (2004) Contraception by Ushercell (cellulose sulfate) in formulation: duration of effect and dose effectiveness. Contraception 70:415-22
Rupp, Richard; Stanberry, Lawrence R; Rosenthal, Susan L (2004) New biomedical approaches for sexually transmitted infection prevention: vaccines and microbicides. Adolesc Med Clin 15:393-407
Stanberry, Lawrence R; Rosenthal, Susan L; Mills, Lisa et al. (2004) Longitudinal risk of herpes simplex virus (HSV) type 1, HSV type 2, and cytomegalovirus infections among young adolescent girls. Clin Infect Dis 39:1433-8
Milligan, Gregg N; Chu, Chin-Fun; Young, Christal G et al. (2004) Effect of candidate vaginally-applied microbicide compounds on recognition of antigen by CD4+ and CD8+ T lymphocytes. Biol Reprod 71:1638-45

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