CONRAD provides leadership in reproductive health by advancing microbicide candidates through preclinical discovery, clinical trials and bringing them to the marketplace.
In 1988, CONRAD pioneered the microbicide research field by developing the first spermicide/virucide screening program. Since then, CONRAD’s network of scientists has evaluated more than 3,000 microbicide/contraceptive compounds. As a result of CONRAD’s extensive work evaluating microbicide candidates, a preclinical testing algorithm that includes assays to evaluate compounds for efficacy, cervicovaginal safety and pharmacokinetics and pharmacodynamics was developed and is now a reference for the field.
In Vitro Research: CONRAD has a pipeline of anti-HIV microbicide agents that are undergoing preclinical characterization, and is continuously adding new agents to target HIV. CONRAD has developed a network of investigators to ensure that any potential microbicide lead can be rapidly characterized in terms of its antimicrobial, contraceptive and local safety properties. Additionally, investigation of biomarkers that potentially signal microbicide-induced mucosal damage is underway.
Formulations: Microbicide candidates must be safe, efficacious, stable, and in a form acceptable to women. These characteristics, particularly challenging for delivering multiple active ingredients in a single vehicle, must be evaluated through stringent testing, including in vivo pharmacokinetic and toxicology studies. CONRAD scientists are working to develop multi-target combination microbicide products that are safe and that will inhibit HIV replication at different points along the virus life cycle, provide a strong barrier to the development of resistance, and remain stable within a suitable delivery system.
Animal Models: CONRAD is refining various animal models of vaginal infection by STI pathogens, including HIV, as part of the development necessary for attaining nontoxic, broad spectrum vaginal microbicides. Immune responses of small animals do not reliably predict those of people. Thus, the development of small animal models that can produce immune responses similar to those produced in humans is critical to determining how best to block HIV entry and transmission, and CONRAD scientists have been involved in these endeavors. Recent work has successfully humanized BLT mice, making them capable of producing human CD4(+) T cells that can be infected with HIV. CONRAD scientists are extending this model to study the effects of various microbicides and to determine how the herpes virus enhances HIV transmission in women. CONRAD researchers also developed an EcoHIV mouse model, in which the HIV envelope is genetically altered by replacing gp120 with gp80 from ecotropic murine leukemia virus, allowing the mice to become infected with HIV. CONRAD scientists are using these models to study the efficacy of various microbicides.
Safety: CONRAD is committed to the development of safe vaginal microbicides. CONRAD researchers are working to improve preclinical safety assessments through the development, standardization and validation of in vitro and in vivo cell-based assays of cytotoxicity and proinflammatory cytokines.