Therapy and Prophylaxis for Genital Tract Infection

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 Recent findings have revealed that N gonorrhoeae subverts the immune system for its own benefit by eliciting innate responses that it can survive and by suppressing specific adaptive responses that would eliminate it However this induced immunosuppression can be reversed by treatments that effectively redirect the immune response against N gonorrhoeae In a Phase I SBIR project proof of principle has been established for a novel strategy of therapy and prophylaxis against genital gonococcal infection using a mouse model that is accepted as the only currently available animal model A proprietary product developed by TherapyX Inc consisting of interleukin IL encapsulated in biodegradable microparticles for sustained release is administered intravaginally in mice infected with N gonorrhoeae This treatment termed GenX induces anti gonococcal T cell and antibody responses against the existing gonococcal infection both accelerating its clearance and generating protection against re infection with homologous and heterologous strains for at least several months In this Phase II application the dose regimen of GenX will be optimized and initial pharmacokinetics studies on its distribution and uptake after intravaginal administration will be performed in preparation for subsequent toxicological testing in nonhuman primates The mechanisms of cross protection against diverse strains of naturally occurring N gonorrhoeae will be determined to substantiate the scientific basis for the treatment and to identify parameters of protective immunity that will need to be tested ultimately in humans In preparation for clinical trials manufacturing scale up and product evaluation for batch consistency purity uniformity stability and other characteristics will be performed The data obtained in these studies will then be used to create a primate toxicology plan Along with the preclinical data this toxicology plan will be incorporated into a briefing package that will b submitted to the FDA in a request for a Type C Meeting PUBLIC HEALTH RELEVANCE Gonorrhea is the second most frequent notifiable infectious disease in the United States the Centers for Disease Control report andgt cases annually and world wide incidence is estimated at andgt million new infections per year No vaccine is available and the emergence of multiple drug resistant strains now raises serious and urgent concerns over future treatment options This proposal seeks to develop a novel strategy of immune intervention against gonorrhea by redirecting the hostandapos s immune response to generate effective immunity that eliminates an existing infection and protects against re infection