Core B - Functional Immunology Core (CIIG)

Henry M. Jackson Fdn For The Adv Mil/Med, Rockville MD

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT The overall objective of Core B: Host Immune Response Core is to provide comprehensive and consistent immune monitoring for the Center for Immunological Interventions against Gonorrhea (CIIG). This will help the Center to develop and characterize vaccine, therapeutic, and diagnostic candidates in a rigorous and systematic manner. Core B will provide all Projects with centralized assays to evaluate immune responses elicited by Neisseria gonorrhoeae vaccine and therapeutic candidates. The Core will also develop and validate standardized assays for pre-clinical and clinical studies to position products on a feasible path for licensure by the end of the five-year funding period. While doing so, the Core will help identify correlates, surrogates and mechanisms of protection against gonorrhea. Thus Core B is critical to the success of the CIIG. To ensure successful completion of the projects in the CIIG, Core B proposes the following Specific Aims. Aim 1: Humoral and cellular immune response profiling: We will provide high-throughput evaluation of antibody quantity, quality (avidity), and isotype profile in serum and mucosal washes after immunization. We will comprehensively immunophenotype lymphoid and genital tract tissue following immunization and pathogen challenge, and we will profile systemic and genital biomarker responses using multiplex arrays. Aim 2: Evaluation of protective mechanisms: We will measure the serum bactericidal activity and opsonophagocytic killing activity of serum and mucosal washes after immunization. We will monitor T cell activation by performing in vitro antigen restimulation and analyzing by flow cytometry, FluoroSpot, and multiplex arrays. We will provide in vitro models of human genital epithelial cells to evaluate N. gonorrhoeae colonization and inflammatory responses in the context of immunization and novel therapeutics. Aim 3: Preclinical and clinical assay development and validation: We will expand assays including multiplex antigen binding, serum bactericidal activity, and opsonphagocytic killing to a panel of currently circulating N. gonorrhoeae isolates. Antibodies selected for lateral flow diagnostics will be similarly tested for reactivity. Product-specific immunogenicity and efficacy assays will be selected in conjunction with Core D to support product advancement through IND-enabling preclinical and phase I/II clinical studies, in line with current NIH/DMID guidelines. Core B will work closely with the CIIG PI and all Projects and Cores to ensure that the milestones of the CIIG are achieved in a rigorous, comprehensively- documented, reproducible, and timely manner. In these ways Core B will help the CIIG identify vaccine, therapeutic, and diagnostic leads for deployment to combat gonorrhea, a major antibiotic resistance public health concern.