Sexually transmitted infections (STIs) represent a major cause of reproductive morbidity and mortality in women, at an estimated annual health care cost in the United States (US) of $16 billion. Of the 20 million new infections in the US each year, human papillomavirus (HPV) and Chlamydia trachomatis (CT) are by far the most common. While asymptomatic in most women, both infections have the potential for serious adverse outcomes. Infection with one or more of 14 high-risk HPV genotypes is attributable to the development of nearly all invasive cervical cancer and its precursor lesions, cervical intraepithelial neoplasia (CIN). Excisional treatment of high-grade CIN in young childbearing women can result in serious pregnancy complications including preterm deliveries. Infection with HPV6/11, attributable to more than 90% of genital warts can have significant physical morbidity and psychosocial consequences especially in populations who are refractory to treatment and CT infection can cause serious complications such as pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. In the US, despite the availability of HPV and CT screening and treatment and in the case of HPV, efficacious first-generation vaccines, over 39.5 million women aged 14-59 years are estimated to be currently infected with HPV and in 2011, nearly 1.5 million cases of CT infection were reported to the US Centers for Disease Control and Prevention. Novel approaches are critical to understanding the continued high burden of these infections and the barriers to and successes of public health interventions. The overarching goal of this application is to establish an integrated, interdisciplinary STI Cooperative Research Center (STI-CRC) uniquely positioned to adopt a synergistic approach bridging gaps to (1) understand basic epidemiologic data on STI burden, (2) understand STI natural history and burden of disease, (3) advance basic science research for STI vaccines including development of appropriate animal models, high throughput antigen discovery and novel antigen delivery systems, (4) conduct basic studies in clinical settings to expand the overall knowledge base on mucosal immunity in the genital tract; and (5) evaluate the effectiveness of real-world STIs prevention and associated outcomes. The investigators that come together to form this STI-CRC are international leaders in epidemiology, immunology, biostatistics and informatics and vaccine development, with particular expertise in HPV, CT and STI co-infections.