Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix in Healthy Adolescents: A Randomized Phase IIIb Multicenter Study.

ABSTRACT

INTRODUCTION: Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents. METHODS: In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 332 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 18) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status. RESULTS: A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified. CONCLUSIONS: These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents. TRIAL REGISTRATIONS Clinicaltrials.gov, NCT04490018; EudraCT 2020-001665-37; WHO U1111-1249-2973.

MenACYW conjugate vaccine has been made to protect against meningococcal disease caused by four common types of bacteria (germs) called Neisseria meningitidis (or meningococcus), A, C, W, and Y. Many people, particularly adolescents, have the germs of this disease in their nose or throat, and therefore may develop the disease or transmit the bacteria to other people. Hence, adolescent meningococcal vaccination against serogroups ACWY is increasingly recommended in several countries. This study assessed the immune response to these serogroups in healthy adolescents after one dose of MenACYW conjugate vaccine or Nimenrix®, a meningococcal licensed vaccine. Moreover, the immune response and safety were assessed when the vaccines were given alone or when given concomitantly with other adolescent vaccines, including the human papillomavirus (9vHPV) and tetanus, diphtheria, pertussis, and poliomyelitis (Tdap-IPV) vaccines. A total of 463 adolescents (aged 10­17 years) participated in this study and received either MenACYW or Nimenrix® alone, or MenACYW concomitantly with 9vHPV and Tdap-IPV vaccine. The immune response induced by MenACYW was as good as the immune response induced by Nimenrix®, and when given alone or concomitantly with 9vHPV and Tdap IPV vaccines. None of the participants experienced any serious side effects of any vaccine. The most common non-serious side effects were injection site pain, muscle pain, and headache. These data support the use of MenACYW in adolescents, with or without concomitant administration with 9vHPV and Tdap-IPV, which may help to increase the number of adolescents vaccinated.