Vaccine fails to prevent gonorrhoea in Australian study

A trial of a vaccine against gonorrhoea found that it was no more effective than a placebo, in a result described as “unexpected and somewhat disappointing, but very clear” when presented to the Conference on Retroviruses and Opportunistic Infections (CROI 2026) in Denver last week.

Professor Kate Seib of Griffith University in Australia was presenting the results of the GoGoVax study of the 4CMenB vaccine (Bexsero). This is a vaccine given to children to prevent meningitis B. But the bacteria that cause meningitis and gonorrhoea are closely related (both of the genus Neisseria) and observational studies suggested that the vaccine might prevent 33-40% of infections. This was the evidence that has led the UK to roll out the vaccine to gay and bisexual men at higher risk of infection.

Background

There are 82 million cases of gonorrhoea a year worldwide and it particularly affects people at risk of HIV. One in nine people in populations as different as gay and bisexual men in Seattle, US and young women in South Africa acquire gonorrhoea every year, and although its symptoms are usually fairly mild, it is thought to cause from 8 to 30% of cases of pelvic inflammatory disease in women, a major cause of infertility. More rarely, in 0.5 to 3% of cases in both men and women, it becomes a more severe systemic illness that can manifest as joint inflammation, skin lesions and heart disease.

Also of great concern is the fact that Neisseria gonorrhoeae easily acquires resistance to antibiotics. It is now resistant, partly or completely, to several classes of antibiotics and we currently only have one drug, ceftriaxone, that works against most infections. Two new antibiotics, gepotidacin and zoliflodacin, were licensed by the US Food and Drug Administration in December 2025 to treat multi-drug-resistant gonorrhoea – though there have already been cases of resistance to the new drugs.

In the UK, diagnoses of gonorrhoea more than doubled between 2013 and 2022, from 37,150 to 82,592 in 2022. Last year, the UK’s National Health Service began offering the Bexsero vaccine to people at high risk of gonorrhoea, and the Galicia region of Spain has done the same.

It is therefore crucial, as Professor Seib said, “to keep on investigating new methods of gonorrhoea prevention”, despite setbacks  – as in this study.

The study

In the GoGoVax study, 620 gay and bisexual men and trans and non-binary people were randomised to receive either Bexsero or a placebo, in two shots three months apart. If the vaccine had proven efficacious, the placebo recipients would have been offered the vaccine at the end of the two-year study.

Five hundred and eighty-seven people received both doses and attended all clinic visits, which consisted of three-monthly STI check-ups and – at months six, 12 and 24 – tissue samples from infection sites (urethra, rectum or throat) and sexual behaviour questionnaires.

Participants’ average age was 34, 98% were cisgender men, 10% had HIV, 90% had had gonorrhoea before and 19% had had syphilis before. Sixty per cent had had more than ten partners in the last six months, and 35% said they never used condoms (only 1.2% always used them).

Unfortunately, the vaccine offered zero protection on almost every measure. The annual incidence of a first episode of gonorrhoea (i.e. the chance of getting a gonorrhoea diagnosis in the study’s first year) was 48%, in both the vaccine and placebo arms, and the incidence of any infection including repeat ones was 60% and 61% in the vaccine and placebo arms.

The incidence of symptomatic gonorrhoea was 9% on the vaccine and 9.5% on placebo (so less than one in five infections had symptoms).

Incidence in the HIV-positive participants was 51% in the vaccine recipients but 87% on placebo, a 41% difference that might look promising. But with relatively few HIV-positive participants, this translated to 18 infections on vaccine versus 20 on placebo, a difference that was not statistically significant. The same applied to other small subgroups such as transgender/non-binary people and younger men.

Annual incidence in the three possible infection sites was 29% in both throat and rectal infections, for both vaccine and placebo recipients. In urethral/genital infections it was 10% in vaccine and 9% in placebo recipients – again, not statistically significant.

This is the second randomised trial of 4CMenB in gay and bisexual men to not show efficacy. In the French DoxyVAC study, the 22% reduction in gonorrhoea in vaccine recipients was not statistically significant.

However, Seib said, results should not be generalised to other populations, especially cisgender women, where the route of infection and risk of complications are different. Two other large randomised studies are underway: the MAGI study in 2200 men and women in the US, Malawi and Thailand, and the BIYELA study in 1100 young women in South Africa.

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