O01.6 Meningococcal vesicle vaccines deleted for major outer membrane proteins enhance gonococcal clearance in a murine model

Background With an incidence rate of 106 million infections a year, Neisseria gonorrhoeae has a significant effect on global morbidity. Rapid development of gonococcal antibiotic resistance, and reports of treatment failures with last-line cephalosporins, has caused the Centers for Disease Control and Prevention to label N. gonorrhoeae as an urgent threat and has sparked renewed interest in development of a gonococcal vaccine. Methods In this study, we immunized mice with detoxified outer membrane vesicles (dOMVs) isolated from the closely-related pathogen Neisseria meningitidis and examined the effect on gonococcal clearance in a murine vaginal colonization model. dOMV vaccines were derived from (1) wild type (WT) bacteria, (2) an isogenic strain (ΔABR) deleted for expression of the major outer membrane proteins PorA, PorB, and RmpM, or (3) an isogenic strain (OCh) deleted for PorA and expressing a varying PorB sequence type relative to the parental strain. ELISAs were used to evaluate anti-dOMV IgG and IgA antibody titers present in sera and vaginal washes. Sera were also used to identify potential gonococcal vaccine antigens using immunoblot and immunoprecipitation experiments. Results Although vaccination with WT dOMVs significantly enhanced gonococcal clearance relative to adjuvant-only controls, vaccination with ΔABR dOMVs resulted in clearance of a higher percentage of mice relative to WT dOMV-vaccinated mice one week post-immunization. Higher levels of clearance in ΔABR dOMV-immunized mice correlated with significantly increased vaginal IgA titers and enhanced immunogenicity of unique meningococcal protein antigens. Conclusion Immunization with meningococcal dOMVs deleted for PorA, PorB, and RmpM promotes gonococcal clearance in a murine model. Deletion of the major porins likely enhances immunogenicity of proteins that are less abundant on the meningococcal surface but exhibit a high degree of homology with corresponding gonococcal proteins, suggesting the potential utility of these dOMVs as a broadly cross-protective Neisseria vaccine. Disclosure No significant relationships.