Published July 8, 2026
N Engl J Med 2026;395:349-361
DOI: 10.1056/NEJMoa2516739
Abstract
Background
No vaccines are currently licensed for the prevention of Neisseria gonorrhoeae infection. Observational studies suggest that the four-component meningococcal serogroup B vaccine (4CMenB) may reduce the risk of gonorrhea.
Methods
In this multicenter, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, men who have sex with men (MSM) to receive two doses of 4CMenB or placebo. All the participants had recently received a diagnosis of N. gonorrhoeae infection or infectious syphilis and either tested negative for human immunodeficiency virus (HIV) and were receiving HIV preexposure prophylaxis or were living with HIV. Screening for sexually transmitted infections, including N. gonorrhoeae nucleic acid amplification testing of samples obtained from urogenital, anorectal, and oropharyngeal sites, was performed quarterly for 2 years. The primary outcome was a first N. gonorrhoeae infection after the receipt of vaccine or placebo in the per-protocol population (participants who received both 4CMenB or placebo doses, attended at least two scheduled follow-up visits after the second dose, and did not meet any exclusion criterion pertinent to the assessment of efficacy).
Results
From July 2021 through May 2023, a total of 654 participants underwent randomization, of whom 587 were included in the primary analysis. The incidence of N. gonorrhoeae infection was 48.1 events per 100 person-years (160 events among 296 participants) in the 4CMenB group and 47.8 events per 100 person-years (155 events among 291 participants) in the placebo group (incidence rate ratio, 1.01; 95% confidence interval [CI], 0.80 to 1.26; P=0.97), for a vaccine efficacy of −0.5% (95% CI, −26.2 to 19.9). Vaccine efficacy was 5.5% (95% CI, −56.0 to 42.8) for symptomatic infection, −6.4% (95% CI, −47.5 to 23.2) for asymptomatic infection, and −20.0% (95% CI, −90.2 to 23.9), −1.2% (95% CI, −33.0 to 23.0), and 2.6% (95% CI, −27.7 to 25.7) for urogenital, anorectal, and oropharyngeal infection, respectively. Serious adverse events occurred in 4.7% of the participants in the 4CMenB group and in 2.8% of those in the placebo group.
Conclusions
4CMenB did not result in a lower incidence of N. gonorrhoeae infection than placebo among MSM who were at high risk for gonorrhea. (Funded by the Australian National Health and Medical Research Council and GSK; GoGoVax ClinicalTrials.gov number, NCT04415424.)
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Notes
This article was published on July 8, 2026, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by a grant (GNT1182443) from the Australian National Health and Medical Research Council and by GSK.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the members of the GoGoVax Protocol Steering Committee not already listed as authors; the nonauthor coinvestigators and coordinators, pharmacists, drug managers, and clinical and laboratory staff at the trial sites; and the trial participants.
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History
Published online: July 8, 2026
Published in issue: July 23, 2026
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Cited by
- Gonorrhoea vaccine: Australian study suggests England’s “world first” rollout may not work, BMJ, 394, (e100281), (2026).https://doi.org/10.1136/bmj-2026-100281
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Facts Only
* A multicenter, double-blind, randomized, placebo-controlled trial was conducted.
* Participants were men who have sex with men (MSM).
* The intervention involved two doses of the four-component meningococcal serogroup B vaccine (4CMenB) or placebo.
* Participants had recently been diagnosed with *N. gonorrhoeae* infection or infectious syphilis and tested negative for HIV, or were receiving HIV preexposure prophylaxis/living with HIV.
* Screening for STIs, including nucleic acid amplification testing of *N. gonorrhoeae*, was performed quarterly for two years.
* The primary outcome was a first *N. gonorrhoeae* infection after vaccine receipt or placebo.
* In the 4CMenB group, the incidence rate was 48.1 events per 100 person-years (160 events among 296 participants).
* In the placebo group, the incidence rate was 47.8 events per 100 person-years (155 events among 291 participants).
* The incidence rate ratio for *N. gonorrhoeae* infection was 1.01 (95% CI, 0.80 to 1.26; P=0.97).
* Vaccine efficacy for symptomatic infection was 5.5% (95% CI, −56.0 to 42.8).
* Vaccine efficacy for asymptomatic infection was −6.4% (95% CI, −47.5 to 23.2).
* Serious adverse events occurred in 4.7% of the 4CMenB group and 2.8% of the placebo group.
Executive Summary
A randomized, placebo-controlled trial investigated the effect of the four-component meningococcal serogroup B vaccine (4CMenB) on the incidence of *Neisseria gonorrhoeae* infection in men who have sex with men (MSM). The study involved 654 participants randomized 1:1 to receive either 4CMenB or a placebo. Participants had recently been diagnosed with *N. gonorrhoeae* infection or infectious syphilis, were HIV-negative or on prophylaxis, and underwent quarterly screening for STIs over two years. The primary outcome assessed the risk of a first *N. gonorrhoeae* infection after vaccine receipt.
The results indicated that there was no statistically significant difference in the incidence rate ratio of *N. gonorrhoeae* infection between the 4CMenB group and the placebo group (incidence rate ratio of 1.01; P=0.97). Vaccine efficacy estimates varied by type of infection: 5.5% for symptomatic infection, -6.4% for asymptomatic infection, and various small changes for specific types of infection (urogenital, anorectal, or oropharyngeal). Serious adverse events occurred at rates of 4.7% in the vaccine group and 2.8% in the placebo group.
The overall conclusion was that 4CMenB did not result in a lower incidence of *N. gonorrhoeae* infection than placebo among high-risk MSM.
Full Take
The finding that the 4CMenB vaccine did not reduce the incidence of *N. gonorrhoeae* infection compared to placebo in this high-risk MSM population suggests a significant gap between prophylactic vaccination strategies and actual disease outcomes for gonorrhea. The lack of statistically significant benefit, despite observable small efficacy percentages across different infection types (e.g., 5.5% for symptomatic), requires deeper scrutiny regarding vaccine targets, exposure dynamics, or the sensitivity of the study design to capture true risk reduction in this context.
The heterogeneity in observed efficacy rates—positive for symptomatic infection but negative or negligible for asymptomatic or specific genital infections—points toward potential complexities in how meningococcal vaccination interacts with gonococcal transmission routes or clinical presentation. The null result, coupled with the observation that serious adverse events were slightly higher in the vaccine group, prompts an examination of the real-world public health implications: if a widely available vaccine does not demonstrably lower STI rates in a vulnerable cohort, it challenges the assumption that vaccination is a reliable mechanism for controlling sexually transmitted infections. Future research must address whether the baseline risk or the specific routes of transmission relevant to gonorrhoeae are adequately addressed by meningococcal serogroup B immunity.
What factors might account for this outcome? Does the vaccine target a shared immune response that does not directly mitigate *N. gonorrhoeae* colonization, or do the observed effects relate to broader immune modulation in at-risk individuals? Further investigation into the correlation between meningococcal immunity and gonorrhea transmission dynamics is necessary to establish whether this finding represents a limitation of the intervention itself or a reflection of epidemiological reality.
Sentinel — Human
The text is highly structured, presenting clinical trial results with necessary statistical detail, strongly suggesting an origin in peer-reviewed medical literature rather than synthetic generation.