Research Summary

Randomized Trial Finds 4CMenB Does Not Reduce Gonorrhea in MSM With Recent STIs

Edited by:
Ashton L. Stahl

Key Highlights

  • The trial included 654 participants at 7 Australian clinics.
  • Gonorrhea incidence was similar with 4CMenB and placebo.
  • Estimated vaccine efficacy was −0.5% (95% CI, −26.2% to 19.9%).
  • Serious adverse events occurred in 4.7% and 2.8% of participants, respectively.

The 4-component meningococcal serogroup B vaccine (4CMenB) did not reduce the incidence of Neisseria gonorrhoeae infection among men who have sex with men (MSM) at high risk for gonorrhea, according to a study published in The New England Journal of Medicine. The Australian GoGoVax trial found nearly identical infection rates among participants receiving 4CMenB and those receiving placebo.

The multicenter, double-blind, randomized, placebo-controlled trial enrolled adults aged 18 to 50 years who had recently received a diagnosis of gonorrhea or infectious syphilis. Participants were either living with HIV or were HIV-negative and receiving, or planning to receive, HIV pre-exposure prophylaxis. The study was conducted at 5 publicly funded sexual health clinics and 2 private primary care clinics in eastern Australia.

Researchers randomly assigned 654 participants in a 1:1 ratio to receive 2 intramuscular doses of 4CMenB or saline placebo 3 months apart. Participants underwent quarterly screening for sexually transmitted infections over 2 years, including nucleic acid amplification testing for N gonorrhoeae using samples from urogenital, anorectal, and oropharyngeal sites. The primary outcome was a first gonorrhea infection beginning at least 4 weeks after the second dose in the per-protocol population.

Study Findings

The primary analysis included 587 participants: 296 in the 4CMenB group and 291 in the placebo group. Their mean age was 34.2 years, 98.3% identified as men, 9.5% were living with HIV, and 89.6% had experienced gonorrhea during the previous 18 months.

During a mean follow-up of 1.97 years, the incidence of a first gonorrhea infection was 48.1 cases per 100 person-years in the 4CMenB group and 47.8 cases per 100 person-years in the placebo group. The incidence rate ratio was 1.01 (95% CI, 0.80-1.26; P = .97), corresponding to a vaccine efficacy of −0.5% (95% CI, −26.2% to 19.9%).

Vaccine efficacy was 5.5% for symptomatic infection and −6.4% for asymptomatic infection. Estimates were −20.0% for urogenital infection, −1.2% for anorectal infection, and 2.6% for oropharyngeal infection. Serious adverse events occurred in 4.7% of participants receiving 4CMenB and 2.8% receiving placebo; investigators considered 1 event possibly related to the vaccine.

Clinical Implications

According to the study authors, the results provide evidence that 4CMenB is not effective for preventing gonorrhea among MSM at high risk for infection. They suggested that other vaccine targets, implementation strategies, or both may be necessary.

The trial was not powered to assess symptomatic, asymptomatic, site-specific, or subgroup outcomes. Its concentration on a high-risk population also limits the generalizability of the results to women and people with little or no previous gonorrhea exposure.

Expert Commentary

“4CMenB did not result in a lower incidence of N gonorrhoeae infection than placebo among MSM who were at high risk for infection,” the researchers concluded.

Reference

Seib KL, Donovan B, Jin F, et al; GoGoVax Study Team. Meningococcal B vaccine to prevent Neisseria gonorrhoeae infection. N Engl J Med. 2026;395(4):349-361. doi:10.1056/NEJMoa2516739