O01.5 A meningococcal native outer membrane vesicle vaccine as a platform for presenting conserved gonococcal antigens

Background Neisseria meningitidis (Nm) outer membrane vesicles (OMV) are treated with detergents to decrease endotoxin activity, which removes lipoproteins and may result in non-native protein structures. Previously, we prepared native OMV (NOMV) vaccines from mutant Nm with genetically attenuated endotoxin and over-expressed Factor H binding protein (FHbp) mutants with reduced binding to human FH. Mice immunized with NOMV-FHbp developed higher and broader meningococcal SBA responses than a control recombinant FHbp vaccine. The NOMV-FHbp also elicited SBA against Neisseria gonorrhoeae (Ng) strain FA1090, which expresses many outer membrane proteins that are highly conserved in both pathogens. In this study, we identify antigens in NOMV-FHbp that elicit SBA against Ng as well as those that elicit blocking antibodies in rhesus macaques to develop a NOMV vaccine with the potential to provide protection against both pathogens. Methods Antiserum from mice immunized with NOMV-FHbp were used to immunoprecipitate antigens from FA1090. The antigens were identified by LC-MS/MS. Antigens that elicit blocking antibodies in macaques were identified by comparing antibody responses that were positive for SBA in mice and macaques with those in macaques that also had antibodies to conserved antigens but lacked SBA against FA1090. Results Antibodies elicited by NOMV-FHbp were reactive with four integral membrane proteins and one lipoprotein in FA1090 that are highly conserved in Nm (≥87% identity), essential for bacterial survival humans, and are known to mediate SBA against Nm and Ng. One of the proteins also mediates Ng adhesion to human cervical cells, which can be blocked by vaccine-elicited antibodies. Blocking antibodies elicited by NOMV-FHbp appear to be directed to Rmp, which is known for this effect. Conclusion An engineered NOMV vaccine containing a few conserved overexpressed antigens and lacking antigens having the potential to elicit blocking antibodies, such as Rmp, may provide broad protection against disease caused by pathogenic Nm and Ng. Disclosure No significant relationships.