Profiling of the serological response to Gonococcus in healthy subjects receiving 4CMenB vaccine

Due to the emergence of antimicrobial resistant Neisseria gonorrhoeae (Ng) strains and the high burden of gonorrhea worldwide, Ng has been prioritized as an urgent public health threat for which the development of an effective vaccine represents a medical need. The incidence of gonococcal cases is expected to rise due to the development of multi-drug resistance. Recent real-world observations of circa 30% effectiveness of the 4CMenB vaccine against gonococcus infections from case-control retrospective studies conducted in several countries could provide useful hint for gonococcal vaccine research. Moreover, a comparative genomic analysis demonstrated that antigens exposed on Outer Membrane Vesicles from New Zealand MenB strain (OMVNZ) and Ng strains show 80-90% homology. Based on the above evidence, investigation to elucidate the role of the immune response induced by 4CMenB vaccine involved in mediating protection against Ng is underway. This project aimed to conduct a serological analysis on pre and post vaccination sera from adult and infant populations receiving 4CMenB vaccination. Specific anti-Ng IgG antibodies were measured by Luminex immunoassay using beads coupled with OMVs from Ng strains and antibody functional activity was assessed by Serum Bactericidal Assay in the presence of human complement (hSBA) against two Ng strains. Binding and functional results showed a specific immune response induced by 4CMenB against Ng strains in about 25% of subjects. We also assessed functional activity by complement C3b deposition on OMV from one Ng strain. Finally, serum IgG titers against Ng antigens were measured to investigate the potential role of those antigens in mediating gonococcus cross-protection, alone or in synergy. A computational analysis uncovered a distinct immune response profile based on LOS pre-immunity, in which 19% of subjects showed evidence of an anti-Ng response induced by vaccination. Although no matching between cross-reaction and vaccine protection can be inferred, our study revealed that 4CMenB sera were cross-reactive against gonococcus for about 20% of the subjects evaluated. This research opens the door for future investigations to comprehend the cross-protective response against gonococcus.