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. 2025 Aug;14(8):1843-1865.
doi: 10.1007/s40121-025-01190-7. Epub 2025 Jul 15.

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered with Routine Pediatric Vaccines: A European Randomized Controlled Trial

Federico Martinon-Torres  1   2   3 , Miia M Virta  4 , Susanna Koski  5   6 , Ignacio Salamanca de la Cueva  7 , Henryk T Szymanski  8 , Samantha Bosis  9 , Anca C Drăgănescu  10   11 , Sven-Arne Silfverdal  12 , Betzana Zambrano  13 , Mandeep S Dhingra  14 , Siham B'Chir  15 , Olga Syrkina  16 , Olga Lyabis  17 , Gustavo A Vasquez  18 , Christine Rehm  14 ; MET58 Study Group
Affiliations

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered with Routine Pediatric Vaccines: A European Randomized Controlled Trial

Federico Martinon-Torres et al. Infect Dis Ther. 2025 Aug.

Abstract

Introduction: The immunogenicity and safety of MenACYW-TT (MenQuadfi®) were compared to another quadrivalent meningococcal conjugate vaccine, MCV4-TT (Nimenrix®), when administered in infants alongside routine childhood vaccines in Europe.

Methods: One set of healthy infants was randomized 1:1 to receive MenACYW-TT (group 1; n = 714) or MCV4-TT (group 2; n = 726) at age 2, 4, and 12-18 months (2 + 1 regimen) concomitantly with routine vaccines (including 10-valent pneumococcal conjugate vaccine). Another set was randomized 1:1 to receive MenACYW-TT in a 2 + 1 regimen (group 3; n = 112) or a 3 + 1 regimen at age 2, 4, 6, and 12-18 months (group 4; n = 108) concomitantly with routine vaccines (including 13-valent pneumococcal conjugate vaccine). Immune responses against meningococcal serogroups A, C, W, and Y were measured by serum bactericidal assay using human complement (hSBA). Non-inferiority of MenACYW-TT versus MCV4-TT was based on hSBA geometric mean titers (GMTs) 30 days post-booster (dose 3; primary endpoint) and rates of seroprotection 30 days post-dose 2 (secondary endpoint) against all vaccine meningococcal serogroups. Immune responses to co-administered vaccines and safety were also assessed. Post hoc, non-inferiority of MenACYW-TT was also assessed based on seroresponse rates 30 days post-booster.

Results: Non-inferiority of MenACYW-TT versus MCV4-TT, based on GMTs post-booster, was demonstrated for serogroups C, W, and Y but not for A. GMTs against serogroups C, W, and Y were 1.5- to 4.5-fold higher with MenACYW-TT than MCV4-TT; those against serogroup A were marginally lower. Antibody responses in groups 3 and 4 against all serogroups were similar to group 1. Non-inferiority of MenACYW-TT based on seroresponse rates post-booster against all serogroups was demonstrated post hoc. No interference with concomitant routine vaccines nor safety concerns were identified.

Conclusions: Consideration of all immunogenicity and safety data generated in this study supports the incorporation of MenACYW-TT into the routine childhood vaccination schedule as a 2 + 1 regimen starting at age 6 weeks.

Gov identifier: NCT03547271.

Keywords: Concomitant vaccine administration; Immunogenicity; Infants; Invasive meningococcal disease; MCV4-TT; MenACYW-TT; Meningitis; Quadrivalent meningococcal vaccines; Safety; Toddlers.

Plain language summary

This study compared the immune response and safety of two vaccines that protect against meningococcal disease caused by serogroups A, C, W, and Y. We compared the MenACYW-TT (MenQuadfi®) vaccine to MCV4-TT (Nimenrix®), a vaccine already licensed for infants in Europe. The vaccines were assessed when administered as a three-dose series (2 + 1 regimen) for infants starting vaccination at age 6 weeks, given alongside routine scheduled childhood vaccines. The MenACYW-TT vaccine appeared to trigger a similar or higher immune response as compared with MCV4-TT based on antibody titers that were measured for the different study groups in our main analysis, except against serogroup A. However, a subsequent unplanned analysis, based on increased individual antibody response compared with baseline, found the two vaccines to be similar across all meningococcal serogroups. Thus, the two vaccines would be expected to provide similar protection against the four meningococcal serogroups. The two vaccines had no effect on the immune response to the co-administered routine vaccines, and no new safety concerns were identified. These results support the use of the MenACYW-TT vaccine in infants from 6 weeks of age.

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Conflict of interest statement

Declarations. Conflict of Interest: Betzana Zambrano, Mandeep Singh Dhingra, Siham B’Chir, Olga Syrkina, Olga Lyabis, Christine Rehm, and Gustavo Vasquez are employees of Sanofi and may hold shares and/or stock options in the company. Federico Martinon-Torres has acted as principal investigator in this trial and also in other randomized controlled trials of Ablynx, Abbot, Seqirus, Sanofi Pasteur MSD, Sanofi Pasteur, Cubist, Wyeth, Merck, Pfizer, Roche, Regeneron, Jansen, Medimmune, Moderna, Novavax, Novartis, and GSK, with honoraria paid to his institution. He also reports consulting or advisory relationship with AstraZeneca, GSK Vaccines SRL, BioNet, Biofabri, Pfizer Inc, Sanofi Pasteur Inc, Seqirus Janssen Pharmaceuticals Inc, and MSD. Susanna Koski acted as a principal investigator for the study reported in this manuscript, which was sponsored by Sanofi. She is an employee of Finnish Vaccine Research (FVR), which conducts clinical vaccine studies for many major vaccine manufacturers, including Sanofi. Henryk T Szymanski reports personal fees and trial fees paid to his institution from MSD, Seqirus, Pfizer, Janssen, and Sanofi Pasteur. Miia Virta, Ignacio Salamanca de la Cueva and Samantha Bosis have no conflicts of interest to declare. Anca Cristina Drăgănescu acted as a principal investigator for the study reported in this manuscript, which was sponsored by Sanofi. Sven-Arne Silfverdal acted as a principal investigator for the study reported in this manuscript, which was funded by Sanofi, and also for other trials sponsored by GSK, Jansen, Medimmune, MSD, and Pfizer. He has been a member of advisory boards for Astra, GSK, MSD, Pfizer, and Sanofi Pasteur, with honoraria to his institution or personal. Ethical Approval: The study was conducted in compliance with the International Conference on Harmonisation guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki. Informed consent was obtained from participants’ parents (or legal guardian) before any study procedures were performed. The protocol and any amendments were approved by applicable independent ethics committees or institutional review boards at each participating site and the appropriate regulatory agencies in each country (Supplementary methods).

Figures

Fig. 1
Fig. 1
Flow of participants through the study. AE adverse event, BL blood sample, LFU lost to follow-up, MCV4-TT quadrivalent meningococcal conjugate vaccine, MenACYW-TT quadrivalent meningococcal polysaccharide tetanus toxoid-conjugate vaccine, PD protocol deviation, V visit, VW voluntary withdrawal by parent(s)/legally acceptable representative(s). *The numbers of participants who received MenACYW-TT (groups 1, 3, and 4) or MCV4-TT (group 2)
Fig. 2
Fig. 2
hSBA vaccine seroprotection (antibody titers ≥ 1:8) 30 days after the second dose of MenACYW-TT (group 1) versus MCV4-TT (group 2) at 4 months of age (a) seroprotection rates and (b) non-inferiority analysis in PPAS. CI confidence interval, hSBA serum bactericidal antibody assay using human complement, MCV4-TT quadrivalent meningococcal conjugate vaccine, MenACYW-TT quadrivalent meningococcal polysaccharide tetanus toxoid-conjugate vaccine, N number of participants, NI non-inferiority, PCV10 10-valent pneumococcal conjugate vaccine. 95% CI of the single proportion calculated from the exact binomial method. 95% CI of the difference calculated from the Wilson score method without continuity correction. The overall non-inferiority was demonstrated if the lower limit of the two-sided 95% CI was > − 10% for all four serogroups. Group 1: MenACYW-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age. Group 2: MCV4-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age
Fig. 3
Fig. 3
hSBA seroresponse 30 days after booster dose of MenACYW-TT (group 1) versus MCV4-TT (group 2) at 12–18 months of age; (a) hSBA seroresponse rate and (b) post hoc non-inferiority analysis in PPAS. CI confidence interval, hSBA serum bactericidal antibody assay using human complement, MCV4-TT quadrivalent meningococcal conjugate vaccine, MenACYW-TT quadrivalent meningococcal polysaccharide tetanus toxoid-conjugate vaccine, N number of participants, NI non-inferiority, PCV10 10-valent pneumococcal conjugate vaccine, PPAS per-protocol analysis set. hSBA vaccine seroresponse was defined as a post-vaccination titer ≥ 1:16 for participants with a pre-vaccination hSBA titer < 1:8, or a post-vaccination titer ≥ fourfold increase from baseline for participants with a pre-vaccination hSBA titer ≥ 1:8. Post hoc non-inferiority assessment: lower limit of the two-sided 95% CI of the difference in hSBA seroresponse rates >  − 10% for all four serogroups. Group 1: MenACYW-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age. Group 2: MCV4-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age.
Fig. 4
Fig. 4
Percentage of participants with hSBA titer (a) ≥ 1:4 and (b) ≥ 1:8 at D0 before dose 1 at 2 months of age, D30 post-dose 2 at 4 months of age, and at D0 before and D30 after the booster at 12–18 months of age for groups 1, 2 and 3. CI confidence interval, D day, hSBA serum bactericidal antibody assay using human complement, MCV4-TT quadrivalent meningococcal conjugate vaccine, MenACYW-TT quadrivalent meningococcal polysaccharide tetanus toxoid-conjugate vaccine, PCV10 10-valent pneumococcal conjugate vaccine, PCV13 13-valent pneumococcal conjugate vaccine. 95% CI of the single proportion calculated from the exact binomial method. group 1: MenACYW-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age. Group 2: MCV4-TT and routine pediatric vaccines (including hexavalent and PCV10) administered at 2, 4, and 12–18 months of age. Group 3: MenACYW-TT and routine pediatric vaccines (including hexavalent and PCV13) administered at 2, 4, and 12–18 months of age
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