EPIC-STI Projects Overview
The Epidemiology and Prevention Interdisciplinary Center for Sexually Transmitted Infections (EPIC-STI).
Expert panels have been convened over the past several years by the US Centers for Disease Control (CDC) and the World Health Organization (WHO) with a mandate to identify barriers to the effective prevention and control of sexually transmitted infections (STIs) and their disease sequelae, including the development of effective vaccines. Among the consensus agreement in research gaps was the need to:
- obtain better basic epidemiologic data on STI burden,
- improve our understanding of STI natural history and burden of disease,
- advance basic science research for STI vaccines including development of appropriate
- animal models, high throughput antigen discovery, and novel adjuvant and delivery systems, and
- conduct basic and translational studies in human clinical settings to expand the knowledge base on mucosal immunity in the genital tract. The goal of this application is to establish an integrated, interdisciplinary Center uniquely positioned to adopt a synergistic approach to bridging these and other research gaps. The investigators that comprise the EPIC-STI are internationally recognized leaders in molecular epidemiology, immunology, and
- vaccine development, with particular expertise in human papillomavirus (HPV) and Chlamydia trachomatis (CT) infections. The EPIC-STI will extend the successful model of the currently funded University of New Mexico -Interdsciplinary HPV Prevention Center (UNM-IHPC) to the epidemiologic description of the burden and impact of other common STIs and co-infections, the development of novel HPV and CT vaccines using broad spectrum epitope mapping and vaccine delivery via highly immunogenic virus like particle (VLP) platforms, and evaluation of the immune response to CT infections using complementary human and mouse studies.
The EPIC-STI projects 1 and 3 will use complementary approaches to fill critical gaps in knowledge needed to improve our understanding of the development of protective host immune response to CT infection. A focus of these synergistic projects will be enhancing the understanding of the immune response at the genital mucosa, including characterization of memory T-cells tracking to the mucosa and how the mucosal immunological microenvironment interacts to affect trafficking or functioning of T-cell responses to CT infection using mouse models. Project 3 provides a detailed and expansive characterization of soluble immune microenvironment in human CT infections and determines whether specific immunologic profiles change following antibiotic treatment and correlate with spontaneous resolution of infection versus susceptibility to reinfection. Translation of the findings from the human studies in Project 3 to animal studies in Project 1 serves to accelerate and refine the mouse model of CT infection and immunity. A core component of these two projects is to develop a more sound understanding of the character and variability of normal immune responses in order to identify deviations that result from infection or that may be associated with protection.
Traditionally vaccines have relied on one strategy - to mimic as closely as possible the immunological consequences of natural infection. Project 2 of the EPIC-STI will utilize a novel bacteriophage virus-like particle (VLP) display system that can be used for both vaccine identification and implementation. We have already used this platform to develop a next-generation HPV vaccine, and one aim of Project 2 is directed towards formulating this vaccine to address both US and global disparities in vaccine affordability and access in rural/remote populations. This highly immunogenic VLP platform will also be employed in the CT components of this Project. CT vaccine candidates will be identified using a high-throughput and sensitive antigen discovery that employs sera resulting from Projects 1 and 3 in parallel with complementary bioinformatics strategies. Synergies will be furthered through the testing of lead vaccine candidates using Dr. Starnbach’s state-of-the-art CT infection model.