Abstract: Antibiotic resistance in the sexually transmitted pathogen, Neisseria gonorrhoeae, has been recognized as a serious emerging public health threat by WHO and the US CDC. An effective vaccine against N. gonorrhoeae would serve as an important tool in the battle against antibiotic resistant N. gonorrhoeae. However, N. gonorrhoeae vaccine development has been hampered by the fact that individuals infected with N. gonorrhoeae do not develop immunity to subsequent infection. As a result, immune responses required for protection from infection have never been determined for N. gonorrhoeae. A mass vaccination campaign in New Zealand with a new vaccine against N. meningitidis serogroup B was followed by a reduced rate of N. gonorrhoeae infections in vaccinated individuals. The vaccine used in New Zealand contained outer membrane vesicles from N. meningitidis that are a component of a US FDA-approved N. meningitidis serogroup B vaccine (4CMenB) and contain many antigens that are highly related to N. gonorrhoeae antigens. Our research team currently uses a unique human experimental infection model to study N. gonorrhoeae in its natural host. This time, when use of the new meningococcal vaccine is not yet widespread within the US, provides a unique and time- sensitive opportunity to test the effectiveness of this vaccine in preventing N. gonorrhoeae using our human challenge model. Furthermore, the proposed clinical trial will allow us to study immune responses to the 4CMenB vaccine and determine which responses are essential to the protective effect of the vaccine. The current proposal requests support for the planning and development of the proposed clinical trial, representing an important step in the development of an effective N. gonorrhoeae vaccine.