A Phase 3 study to assess the safety and immunogenicity of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in healthy infants in the USA and Puerto Rico

A quadrivalent meningococcal tetanus toxoid-conjugate vaccine, MenACYW-TT, has been developed to provide protection against invasive meningococcal disease caused by <i>Neisseria meningitidis</i> serogroups A, C, Y, and W. This Phase 3 study (NCT03537508; April 25, 2018, to September 22, 2023) evaluated the immunogenicity and safety of MenACYW-TT, compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM₁₉₇-conjugate vaccine (MenACWY-CRM), in healthy infants ≥6 weeks of age when administered concomitantly with routine pediatric vaccines in a four-dose series (3 + 1 schedule). Functional antibodies against each meningococcal serogroup were measured by serum bactericidal antibody assay using human complement (hSBA). Non-inferiority was demonstrated for the first co-primary endpoint of seroresponse rates 30 days after the fourth dose at 12-15 months of age, with serogroup-specific seroresponse rates of 79.4%-97.6% and 77.6%-96.4% for MenACYW-TT and MenACWY-CRM, respectively. Non-inferiority was also demonstrated for the second co-primary endpoint based on proportions of participants with hSBA antibody titers ≥1:8 against each serogroup 30 days after the third dose at 6 months of age, with rates of 77.9-99.0% for MenACYW-TT and 67.7-92.9% for MenACWY-CRM. After four doses, hSBA geometric mean titers were comparable for serogroup A and higher for serogroups C, W, and Y with MenACYW-TT versus MenACWY-CRM. Immune responses to all routine pediatric vaccines administered concomitantly with MenACYW-TT were non-inferior to those following concomitant administration with MenACWY-CRM. MenACYW-TT and MenACWY-CRM were overall well tolerated, and the safety profiles of these vaccines were comparable. This study supports the use of MenACYW-TT in infants aged 6 weeks (42 days) or older.<b>Study registration</b>: ClinicalTrials.gov: NCT03537508.