A novel, multiparametric cardiac safety assay using human myocytes

DESCRIPTION (provided by applicant): Genital tract infection with Neisseria gonorrhoeae (gonorrhea) does not induce a state of specific protective immunity and can be acquired repeatedly. Despite public health measures, the disease persists at an unacceptably high frequency; there is no vaccine against it, and resistance even to the latest generations of antibiotics continues to emerge. New findings reveal that N. gonorrhoeae subverts the immune system for its own benefit by eliciting innate responses thatit can survive and by suppressing specific adaptive responses that would eliminate it. This SBIR application seeks to develop a novel strategy utilizing a proprietary product already developed by TherapyX, Inc., for intravaginal application to redirect theimmune response effectively against N. gonorrhoeae. The product will be evaluated in a mouse model of vaginal gonococcal infection that has become accepted as the only currently available animal model. Phase I aims to establish proof-of- principle that the product can induce anti-gonococcal T-cell and antibody responses against the existing infection and accelerate its clearance, and moreover can be recalled to elicit protection against re-infection. The duration of the recall effect, and its ability to afford protection againt different strains of N. gonorrhoeae, will be determined. Successful completion of Phase I will lead to Phase II in which product dosage will be optimized, toxicity will be tested, and cross-protection against a diversity of naturallyoccurring strains of N. gonorrhoeae and long-term efficacy will be evaluated in preparation for clinical trial. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Gonorrhea is the second-most-frequent, notifiable infectious disease in the UnitedStates; the Centers for Disease Control report gt300,000 cases annually and world-wide incidence is estimated at over 60 million new infections per year. No vaccine is available and the emergence of multiple-drug-resistant strains now raises serious concerns over future treatment options. This proposal seeks to develop a novel strategy of immune intervention against gonorrhea, by redirecting the host's immune response to generate effective immunity that eliminates an existing infection and protects againstre-infection.