Despite remaining as one of the leading causes of sexually transmitted infections, with sequelae ranging from ectopic pregnancy and infertility caused by scarring of the reproductive tract to blindness of children born to infected mothers, Neisseria gonorrhoeae has become a forgotten plague. This status has begun to change as multidrug resistant strains of N. gonorrhoeae have emerged, raising the frightening prospect of untreatable infections. Fortunately, as a renewed sense of urgency for the development of a prophylactic gonococcal vaccine has arisen, there have been several great strides made that will facilitate the development of a gonococcal vaccine. First, a new appreciation of the value of phenotypic and genome-based analyses of N. gonorrhoeae variants has led to increased recovery and characterization of bacteria from clinical specimens rather than simple PCR-based molecular diagnosis. Second, new insights regarding immune responses that facilitate N. gonorrhoeae persistence suggest immunological correlates that might afford protective memory. Third, the development of vaginal and transcervical uterine infection in ‘humanized’ mouse models provides an unprecedented ability to study this exquisitely host-adapted pathogen in vivo, facilitating efforts to define the contribution of virulence factors to infection and immunopathogenesis, and providing a tractable model in which to test vaccine candidates. Finally, the re-establishment of human male volunteer urethral challenge models provides a clear path for the definitive validation of high priority vaccine formulations. The material nature of these advances has energized the community to coordinate efforts in the common goal of developing a vaccine to defeat this relentless pathogen.
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