The results of a randomized controlled trial (RCT) indicate that meningococcal B vaccine is not effective at preventing gonorrhea infection in high-risk groups.
The results, presented this week at the Conference on Retroviruses and Infections by a team of Australian researchers, show that among gay and bisexual men with a history of gonorrhea infection who received either the 4CMenB vaccine or placebo, gonorrhea incidence was essentially the same—roughly 48% in both arms.
The 4CMenB vaccine is designed to protect against four serogroups of Neisseria meningitidis, which can cause invasive meningococcal disease. But in recent years, observational studies have suggested 4CMenB might also provide moderate cross-protection against Neisseria gonorrhoeae, the bacterium that causes gonorrhea—one of the most common sexually transmitted infections (STIs) worldwide.
With more than 82 million new gonorrhea infections recorded globally, incidence rising, treatment becoming more complicated because of drug-resistant strains, and no existing gonorrhea vaccine available, public health officials in some countries have eyed meningococcal B vaccines as a potential strategy to combat gonorrhea.
In May 2025, amid a surge of gonorrhea infections in the United Kingdom, England’s National Health Services announced that gay and bisexual men with a recent history of STIs or multiple sexual partners—a group at high risk for gonorrhea infection—would be eligible to receive 4CMenB at sexual health clinics.
But the trial’s lead investigators say their results, along with those from a smaller trial, indicate the need to look at other options.
“Taken together, these two studies provide strong evidence that the 4CMenB meningococcal vaccine is not effective at preventing gonorrhoea in gay and bisexual men who are at high risk of contracting it,” lead investigator Kate Seib, PhD, of Griffith University, said in the press release.
‘Incredibly disappointing’ results
Co-lead investigator Andrew Grulich, PhD, MBBS, of the Kirby Institute called the results “incredibly disappointing,” given the hopes that an effective vaccine could transform efforts to prevent gonorrhea.
“We want men who have received the 4CMenB vaccine in the hope of gonorrhoea prevention to know that the vaccine is very safe and they will have protection against some meningococcal strains,” Grulich said. “However, these men will need to explore other options for prevention of acquisition of gonorrhoea, such as condoms and regular testing.”
In the double-blind, placebo-controlled GoGoVax trial, 587 gay and bisexual men with a documented gonorrhea or syphilis infection in the previous 18 months were randomly assigned 1:1 to receive two doses three months apart for either 4CMenB or placebo from July 2021 through May 2023. The primary outcome was the incidence of a gonorrhea infection at least four weeks after the second scheduled dose.
We want men who have received the 4CMenB vaccine in the hope of gonorrhoea prevention to know that the vaccine is very safe and they will have protection against some meningococcal strains....However, these men will need to explore other options for prevention of acquisition of gonorrhoea, such as condoms and regular testing.
The incidence of a first episode of gonorrhea was 48.1 per 100 person-years (160 infections among 296 participants) in the 4CMenB group and 47.8 per 100 person-years (155 among 291 participants) in the placebo group. The overall vaccine efficacy was –0.5%.
The investigators note that the high rates of previous gonorrhea infection in the trial participants may make them less susceptible to any potential protective effects from the 4CMenB vaccine. The study results, however, cannot be generalized to other populations.
Limits of observational studies
Among the previous studies that suggested 4CMenB may have a cross-protective effect against gonorrhea was a US Centers for Disease Control and Prevention-led surveillance study conducted among 16- to-23-year-olds in Philadelphia and New York City from 2016 through 2018. That study found that receipt of two doses of the vaccine was associated with a 40% reduced incidence of gonorrhea, compared with no vaccination.
"These findings suggest that MenB-4C could offer cross-protection against N gonorrhoeae and provide further evidence supporting feasibility of an effective gonococcal vaccine," the study authors wrote.
But Grulich said the results from these types of observational studies may be affected by confounding factors that can influence the results.
“In GoGoVax, our data demonstrate that good-quality randomisation was achieved, and people randomised to receive vaccine or placebo had balanced levels of confounding factors,” he said. “A properly conducted RCT provides the strongest possible evidence of a cause-and-effect relationship.”
When asked by CIDRAP News in a follow-up email about what these results mean for countries that are offering the 4CMenB vaccine to gay and bisexual men as a strategy to prevent gonorrhea infection, Grulich said he thinks health authorities making that recommendation “should consider our findings.”
