Onofrio, I.; Pagliari, S.; Francis, A.; Quinn, M. E.; Belcher, T.; Dissanayake, S.; Twumasi, C.; Vichos, I.; Grudzien, L. A.; Rollier, C.; MacLennan, C. A.

Background Neisseria gonorrhoeae poses significant public health challenges due to multidrug-resistant gonorrhoeic and severe reproductive health complications of untreated infection. No vaccine is licensed to prevent gonorrhea. However, the meningococcal outer membrane vesicle (OMV)-containing vaccine, 4CMenB, provides moderate cross-protection against gonorrhea. We have recently demonstrated that immunization with gonococcal OMV accelerates clearance of gonococcal infection in mice compared with 4CMenB. Methods To gain insight into possible mechanisms of protection of gonococcal OMV, we evaluated the immunogenicity of GonoVac, a candidate native OMV (nOMV) vaccine against gonorrhea, in mice and rabbits. Three doses of GonoVac were administered intramuscularly from 0.15 to 5 {micro}g in mice, and four doses were used to immunize rabbits at 50 {micro}g per dose, formulated with or without aluminum hydroxide (Al(OH)3). Systemic and mucosal antibody responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay (SBA). Cellular responses were assessed by enzyme-linked immunosorbent spot (ELISpot). Results Immunization with GonoVac formulated with and without Al(OH)3 induced significantly higher levels of gonococcal serum and vaginal IgG, and serum bactericidal antibodies, compared with 4CMenB, which induced no serum killing activity. Serum bactericidal activity of GonoVac correlated with anti-gonococcal IgG and IgG2a levels. Serum IgA levels were minimal. Cellular immune responses were higher in mice receiving GonoVac/Al(OH)3 compared with GonoVac alone. Immunogenicity was similar for GonoVac produced in a bioreactor and shake flasks. Conclusion GonoVac elicits robust and functional immune responses in mice and rabbits compared with 4CMenB, supporting its further development as a promising candidate vaccine against gonorrhea.