Contribution of the different Neisseria gonorrhoeae lipooligosaccharide structural variants to functional responses elicited by GMMA outer membrane vesicles.

Despite decades of research, an effective vaccine against Neisseria gonorrhoeae remains elusive due to the pathogen's antigenic variability and immune evasion capabilities. Retrospective studies of OMV-based meningococcal vaccines have shown a partial effectiveness against gonorrhea, reigniting hopes for a feasible vaccine. Our study focused on the role of gonococcal lipooligosaccharides (LOS), the most abundant antigens on the surface, in stimulating functional immune responses. By employing detoxified OMV from Neisseria gonorrhoeae isogenic strains expressing different LOS glycoforms, we observed that antibodies targeting LOS with long α-chain oligosaccharides correlated with bactericidal activity against a wide range of gonococcal isolates, whereas antibodies that also recognized the β-chain and consequently the 2C7 epitope could achieve a broader bacterial adhesion-inhibiting effect. The results obtained underscore the potential of targeting defined LOS structures to elicit cross-strain protective immunity. Insights from our findings may guide the design of vaccine strategies to combat the threat posed by antimicrobial-resistant gonorrhea.