Evaluating cross-protection: Meningococcal vaccines show effectiveness in gonorrhoea prevention – A systematic review and meta-analysis

Background Gonorrhoea remains a significant global health concern, with men who have sex with men (MSM) being disproportionately affected. Recent evidence suggests that outer membrane vesicle (OMV) meningococcal vaccines, such as the most widely used 4CMenB vaccine, may provide cross-protection against gonorrhoea. Objectives We aimed to evaluate the effectiveness of OMV vaccines against gonorrhoea through a systematic review and meta-analysis. Methods PubMed, Embase, and CENTRAL were searched from inception to 10 July 2024. Original articles were included if they investigated gonorrhoea incidence among recipients of OMV vaccines. Our primary endpoint was the incidence of gonorrhoea among vaccinated and unvaccinated individuals. The risk of bias was assessed using ROBINS-I, and the RoB-2 tools. A random-effects model with a 95 % confidence interval (CI) was applied to estimate pooled effect sizes. The study was registered on PROSPERO, CRD42024530848. Results We identified 12 eligible studies for qualitative analysis. Six retrospective studies and one prospective study were included in the quantitative analysis, of which six investigated the 4CMenB OMV vaccine. The pooled analysis yielded a vaccine effectiveness (VE) of 38 % [95 % CI:22 %–50 %; I 2 = 55 %]. Including only the 4CMenB vaccine, VE was 41 % (OR = 0.59; 95 % CI:0.46–0.76; I 2 = 44 %). Complete vaccination might offer 24 % greater protection compared to partial vaccination (OR = 0.76; 95 % CI:0.31–1.85; I 2 = 86 %). VE declined in 2–3 years post-vaccination. Four studies were rated as low risk, four as moderate risk, and four as having serious risk of bias. The certainty of the evidence was graded as moderate. The main limitations include the retrospective nature and the high heterogeneity of the included studies. Conclusions OMV vaccines offer moderate protection against gonorrhoea. 4CMenB OMV vaccine should be prioritised for sexually active individuals over non-OMV alternatives, with emphasis on completing the full vaccination series. Consideration should be given to administering 4CMenB to high-risk MSM groups specifically for gonorrhoea prevention.