Vaccination for Gonorrhoea: Where Are We Now, and What Comes Next?

Gonorrhoea, caused by Neisseria gonorrhoeae, is a common bacterial sexually transmitted infection and a major global health burden, with more than 80 million new cases estimated annually. There is currently no licensed vaccine, and increasing antimicrobial resistance has renewed the urgency of vaccine development. However, vaccines licensed to prevent invasive meningococcal disease, caused by the closely related bacterium Neisseria meningitidis, may provide cross-protection against N. gonorrhoeae. Observational studies have associated outer membrane vesicle-containing serogroup B meningococcal vaccines with reduced gonorrhoea rates, with estimated effectiveness of approximately 30%. The four-component meningococcal group B vaccine (4CMenB) contains antigens with gonococcal homologues and induces cross-reactive immune responses in both humans and animal models. These findings have supported the implementation of targeted 4CMenB immunisation programmes for people at high risk of gonorrhoea in the UK and Galicia, Spain. However, the recently reported GoGoVax trial and other randomised controlled trials in men who have sex with men (MSM) at high risk of infection have not demonstrated protection against gonorrhoea. Differences in study design, populations, exposure intensity, endpoints and residual confounding may explain the divergence between observational and randomised findings. Ongoing trials in other populations, together with post-implementation surveillance in the UK, will provide important evidence regarding the effectiveness of 4CMenB in different settings. Several gonococcus-specific vaccine candidates are also advancing through preclinical and clinical development. Future progress will benefit from validated correlates of protection, improved understanding of protective mucosal immunity across different anatomical sites and evaluation of vaccine efficacy across diverse populations and exposure settings.