Gonorrhea rates and antibiotic resistance are both increasing. Neisseria gonorrhoeae (Ng) is an exclusively human pathogen and is exquisitely adapted to its natural host. Ng can subvert immune responses and undergoes frequent antigenic variation, resulting in limited immunity and protection from
reinfection. Previous gonococcal
vaccine efforts have been largely unsuccessful, and the last
vaccine to be tested in humans was more than 35 years ago. Advancing technologies and the threat of untreatable
gonorrhea have fueled renewed pursuit of a
vaccine as a long-term sustainable
solution for
gonorrhea control. Despite the development of a female mouse model of genital gonococcal
infection two decades ago, correlates of immunity or protection remain largely unknown, making the gonococcus a challenging
vaccine target. The controlled human urethral
infection model of
gonorrhea (Ng CHIM) has been used to study gonococcal pathogenesis and the basis of anti-gonococcal immunity. Over 200 participants have been inoculated without serious adverse events. The Ng CHIM replicates the early natural course of urethral
infection. We are now at an inflexion point to pivot the use of the model for
vaccine testing to address the urgency of improved
gonorrhea control. Herein we discuss the need for
gonorrhea vaccines, and the advantages and limitations of the Ng CHIM in accelerating the development of
gonorrhea vaccines.