This is a Phase 3, double-blinded, randomised placebo-controlled, multi-centred trial evaluating the efficacy of the four-component meningococcal B vaccine, 4CMenB (Bexsero®), in the prevention of Neisseria gonorrhoeae infection.The target population for this trial is GBM+, either HIV-negative and on PrEP or HIV-positive, who had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with greater gonorrhoea risk). This population has the highest known gonococcal incidence and are recommended under Australian guidelines to attend clinics 3-monthly for comprehensive sexual health screening, including Nuclei acid amplification test (NAAT)-based screening of urine, and pharyngeal and anal specimens for N. gonorrhoeae infection. 730 participants will be enrolled and randomised 1:1 and stratified by clinical sites to receive two doses of 4CMenB vaccine or a matching placebo at 0 and 3 months by intramuscular injection. Recruitment will occur over a 12-month period and all participants will be followed up 3-monthly over a period of 2 years. Participants, their study clinicians and study researchers assessing the outcomes will be blinded to the treatment arm (vaccine or placebo). Participants will be required to attend approximately 10 study visits. Participants may attend additional visits if they have been diagnosed with gonorrhoea infection (symptomatic or asymptomatic) or have a postitive gonorrhoea NAAT test when they return for test of cure. Potentially eligible individuals will be screened within 14 days of baseline (the visit when the first dose of study treatment is administered). Randomisation can be conducted any time between screening and baseline. Screening, randomisation and baseline can occur on the same day if the required HIV result(s) and drug kit (containing 4CMenB or placebo) are available for a participant in the clinic. At screening, study clinicians will conduct the informed consent process with a participant and the informed consent will be signed by both the study clinician and the participant. Eligibility criteria will be checked and a review of medical history (including vaccination history for 4CMenB, prior known meningococcal disease, recent history of sexually transmitted infections \[STIs\], history of taking PrEP \[for HIV negative individuals\] as well as antibiotic use in the last 3 months) will be conducted. Routine blood, urine and swabs will be collected, and urine pregnancy test will be performed in participants with child-bearing potential. Symptoms of urethritis, proctitis, epididymitis, and cervicitis/vaginitis will be documented. At randomisation (which can occur anytime within screening an baseline), participants will be randomised to receive either the 4CMenB vaccine or the placebo. At the baseline visit, research blood specimen and an oral mucosal exudate swab for immune responses testing will be collected before the administration of the first dose of the study treatment. A 10-minute study questionnaire will be completed by the participants. Participants will return to their study site 3 months after the first dose of study treatment to receive the second dose. Prior to the treatment administration, urine pregnancy test (in participants with child-bearing potential) will be conducted. Symptoms of urethritis, proctitis, epididymitis, and cervicitis/vaginitis will be documented. History of antibiotic use in the last 3 months will also be collected. If a participant has tested positive for gonorrhoea infection, routinely collected culture isolates and NAAT samples will be stored in a study research laboratory for phenotypic antimicrobial resistance (AMR) testing and genotyping. Routine blood, urine and swabs will also be collected. Adverse events and serious adverse events (SAEs) will be recorded but only SAEs will be entered into the study electronic data capture system, and reported to the Sponsor in real time. Three-monthly visits will be conducted over a period of 2 years. The study aims to evaluate the efficacy of 4CMenB in the prevention of N. gonorrhoeae infection.