Background The escalating global incidence of multidrug-resistant Neisseria gonorrhoeae necessitates an effective vaccine. While the meningococcal 4CMenB vaccine offers some cross-protection against gonorrhoea, this protection is limited highlighting the need for a targeted gonococcal vaccine. In this study, we evaluate the durability of immune response and characterise the immunogenicity induced by GonoVac, a native Outer Membrane Vesicle (nOMV) vaccine produced from N. gonorrhoeae GC_0817560lpxL1-, across genetically distinct strains of mouse.Methods We evaluated the longevity of the immune response induced by two and three doses of GonoVac formulated with aluminium hydroxide (Al(OH)3) over a one-year period (49 weeks for C57BL/6 and CD1 mice, 33 weeks for BALB/c mice), compared to the meningococcal group B vaccine, 4CMenB. Identical immunisation schedules were followed in BALB/c, C57BL/6, and CD1 mice. Separately, we examined the impact of Al(OH)3 on GonoVac immunogenicity in all three mouse strains. Serological, mucosal, and cellular responses were assessed using ELISA, serum bactericidal assays (SBA) and ELISpot.Results GonoVac with Al(OH)3 induced robust, long-lasting anti-gonococcal IgG responses in all three strains of mice and significantly higher levels of antibody-dependent complement-mediated killing of gonococci in C57BL/6 and CD1 mice compared with 4CMenB. Immune responses were maintained for up to one year. Serum anti-gonococcal IgG subclass distributions varied across mouse strains and between GonoVac and 4CMenB in the same strain of mouse. GonoVac formulated with and without Al(OH)3 elicited high levels of antibody-dependent complement-mediated killing of N. gonorrhoeae irrespective of mouse strain. While mucosal IgG responses were robust with both GonoVac formulations, Al(OH)3 significantly enhancing cellular immunity in BALB/c and CD1 mice compared with C57BL/6 mice.Conclusions Our findings demonstrate that GonoVac, a preclinical candidate gonococcal nOMV vaccine, induces durable and functional anti-gonococcal immune responses that are higher than 4CMenB, across three commonly used laboratory strains of mice.