Core C - in vivo Efficacy Testing (CIIG)

SUMMARY New prophylactic and therapeutic products are urgently needed to reduce the global burden of gonococcal disease and curb the spread and emergence of antibiotic resistant Ng strains. The overall goal of the In Vivo Efficacy Core (Core C) is to provide centralized in vivo efficacy testing of candidate gonorrhea vaccines and an antibody drug conjugate being developed by the Center for Immunological Intervention against Gonorrhea (CIIG). We are uniquely qualified to meet this goal. Years of collaborative research with academic and industrial colleagues have led to the development of well-established protocols for testing vaccines, antibiotics, and other anti-infectives administered by different parental routes, and topically (vaginal) applied antibodies or microbicides for efficacy against Ng. Available mouse models for product testing in our laboratory include the female mouse model of Ng lower reproductive tract (LRT) infection, an ascending Ng infection model, and a Ng/Chlamydia coinfection model for studying the effect of chlamydial infection on gonorrhea vaccine efficacy. The latter goal is important based on evidence that cross-protection of a licensed serogroup B meningococcal vaccine is reduced in individuals with C. trachomatis infection. To support the CIIG Research Projects in meeting their milestones, we will: i.) test the efficacy of candidate Vesivax®-OMV-NgAg-IAM vaccines in female mouse models of Ng LRT infection and ascending infection (Projects 1 and 3). ii.) develop a more humanized ascending infection model that uses supplementation of mice with soluble host-restricted factors (factor H, C4BP) to be more predictive of the effectiveness vaccines and immunotherapeutics for which host complement defenses play a role in protection, and for testing the mechanism by which an Ng peptide-VLP vaccine confers protection in vivo (Project 2); iii.) test the efficacy of leading CIIG vaccines in mice that are Chlamydia-infected prior to Ng challenge; iv.) test the in vivo safety and efficacy of optimized antibody drug conjugates against Ng (Project 4). Core C will also play a central role in integrating the work of the center by collecting and coordinating the delivery of biosamples from efficacy studies to Core B and to Project labs using specimen transport templates and the central data portals provided by Core D. We will also immunize mice for hybridoma production in collaboration with Project 4. Core C will also meet with Project and Core leaders and Core D prior to each experiment to ensure the correct study design is followed and review the resultant data. These interactive meetings will help fuel synergy within the center, and performed by Core C will play a critical role in the advancement of CIIG deliverables into IND-enabling activities and clinical trials.