Abstract: Rising antibiotic resistance in N. gonorrhoeae poses a serious, global public health threat. Effective control of N. gonorrhoeae is hampered by asymptomatic infections that allow transmission of the bacteria to uninfected individuals and immune evasion by the bacteria that has limited vaccine development efforts. Understanding the natural history of asymptomatic infection and the immunologic responses that are responsible for clearance of infection. We propose a longitudinal study with close surveillance and of follow up individuals with recent N. gonorrhoeae infection who are at high risk for re-infection. This study will provide a rich data set to understand pathogen exposure and infection outcome. It will also provide a set of biologic specimens to study the pathogen and host factors that contribute to infection clearance as well as asymptomatic carriage and/or progression to symptomatic infection. We will conduct analysis of anti-N. gonorrhoeae antibody and cellular immune responses to inform correlates of protective immunity against gonorrhea. Combined this project will provide important new information that will contribute to public health and vaccine development efforts to reduce the spread of N. gonorrhoeae.