Antimicrobial-resistant Neisseria gonorrhoeae (Ng) represents a global public health threat, with both the prevalence of gonorrheal infections and resistance to multiple antibiotics increasing in many parts of the world. Several retrospective case‑control studies, mainly in adolescents and young adults after 4CMenB vaccination campaigns, reported moderate cross‑protection against Ng. Recent 4CMenB efficacy trials conducted in a population at very high risk of Ng infection, failed to detect statistically significant efficacy.
To investigate whether the study population may impact vaccine immunogenicity, we characterized the cross-reactive immune response induced by 4CMenB in a general population of healthy adults and infants.
Specific anti-Ng IgG antibodies were quantified against the outer membrane vesicles (OMVs) from Ng laboratory strains MS11, F62 and FA1090 and additional clinical isolates as well as against the homologous meningococcus B (MenB) NZ98/254. Moreover, serum bactericidal activity was assessed against Ng MS11, F62 and FA1090 laboratory strains. Cross reactivity against Neisserial commensal species and selected recombinant surface MenB /Ng shared antigens was also assessed.
RESULTS
In healthy adults, about 25% of subjects showed a significant fold rise in IgG titers after vaccination against one or more of the tested Ng OMVs. Antibody functionality in adults was strain dependent and did not reflect the IgG titres against the corresponding strain. We also observed in adults the presence of high pre‑existing immunity against some Ng strains that may have limited the observable extent of boosting, while infants showed low baseline immunity and clear vaccine‑induced enhancements in binding and bactericidal activity.
Finally, we investigated whether the high baseline in adults might reflect prior exposure to commensal species and whether the limited boosting might be due to anti-RmpM blocking antibodies.
CONCLUSIONS
4CMenB induces cross-reactive and functional antibodies to Ng. Distinct immunological landscapes were observed between adults and infants, supporting the hypothesis that pre-existing immunity in adults may influence the magnitude, and quality of vaccine-induced functional responses. Further investigations in high risk versus general population are required to shed light on the different outcomes of RWE and RCT studies.
Finally, we identified key antigens for gonococcal immunity induced by 4CMenB.
Funding: GSK