Discussion
meningitis, Meningitis, meningococcal disease
MENINGITIS, DISEASE, MENINGITIS, MENINGOCOCCAL DISEASE
This phase 3 trial demonstrated the immunological non-inferiority of NmCV-5 compared to the licensed, WHO pre-qualified quadrivalent meningococcal conjugate vaccine, MenACWY-D. Non-inferiority was demonstrated in all three age-groups based on both seroresponse rates and GMTs. The vaccine had a comparable safety profile to the licensed vaccine. These data are expected to support the licensure and WHO pre-qualification of NmCV-5, as a pentavalent meningococcal conjugate vaccine, including for serogroup X.The licensure of meningococcal conjugate vaccines, including those targeting novel serogroups, based on immunogenicity rather than efficacy endpoints, is a well-established approach.A comparable approach was used for the licensure of the meningococcal serogroup A conjugate vaccine, MenAfriVac.Finally, there are now early data on the effectiveness of MenACWY-D and other quadrivalent vaccines, also licensed based on immunogenicity. Analyzing serogroup C and serogroup Y breakthrough cases following the introduction of a single adolescent MenACWY-D vaccine dose in the US, vaccine effectiveness was estimated to be between 80 and 85%.The trial had several strengths. Both Mali and The Gambia are in the meningitis belt and are thus representative of a key future target population for NmCV-5, while the findings are also likely to translate to other settings. The consistency of the immune responses across age groups is also reassuring considering the future impact of the vaccine. Finally, the technology used in NmCV-5 production is based on cost-effective methods for carrier protein production, polysaccharide fermentation and purification, and chemical conjugation. Thus, the vaccine is expected to be made available at a cost lower than that of the existing quadrivalent vaccines.The limitation of product licensure based on immunogenicity is acknowledged and generating effectiveness data for NmCV-5, particularly against serogroup X disease, will be important. Furthermore, data on the persistence of immune responses at six- and 12-months will be available in due course and important, particularly considering future routine use of NmCV-5 outside the epidemic response.In addition, high baseline serogroup A GMTs, reflecting prior MenAfriVac campaigns and routine immunization programmes in Mali and The Gambia, limited the seroresponse rates to this serogroup. Nonetheless, post-vaccination titres were considerably above those demonstrated to provide protection against this serogroup, and responses of above 95% to the serogroup have previously been demonstrated in naïve toddlers.Based on the data from this trial, NmCV-5 may emerge as a tool to support meningococcal disease control, particularly across the meningitis belt of sub-Saharan Africa, and thus may contribute to epidemic elimination and the other goals of the Global Roadmap for Defeating Meningitis by 2030.