Assessment of immunogenicity and safety of quadrivalent meningococcal vaccine conjugated with tetanus toxoid (MenACWY-TT) in a 2+1 schedule in infants from the first months of life in the Russian Federation when co-administered with routine pediatric vaccines: a randomized phase III study

<jats:p> <jats:bold>Relevance</jats:bold> . Invasive meningococcal disease (IMD) is one of the most dangerous infectious diseases due to its rapid progression and high risk of fatal outcomes, with infants in their first year of life, starting from the first months, being at greatest risk. Evaluation of the safety and efficacy of co-administration of meningococcal conjugate vaccine MenACWY-TT with pediatric vaccines is necessary for its potential use in the immunization program for infants. <jats:bold>Aims</jats:bold> . To evaluate the immunogenicity and safety profile of MenACWY-TT vaccine administered according to a 2+1 schedule (vaccination at 3 and 6 months, booster at 12 months), when co-administered with National Immunization Schedule vaccines in healthy children in the Russian Federation. <jats:bold>Materials and Methods.</jats:bold> An open-label, randomized, multicenter, active-controlled Phase III study was conducted at 8 centers in the Russian Federation. The immunogenicity and safety of MenACWY-TT immunization according to a 2+1 schedule at 3, 6, and 12 months of age co-administered with National Immunization Schedule vaccines, were studied. The study enrolled 225 healthy infants who were randomized in a 2:1 ratio to the MenACWY-TT + routine vaccines group (n = 150) or the comparator group receiving routine vaccines only (n = 75). Immunogenicity against meningococcal serogroups A, C, W, and Y was determined by serum bactericidal assay using human complement (hSBA), and in a subset of vaccinated participants, additionally with rabbit complement (rSBA). Safety was assessed for 30 days after each injection; monitoring for serious adverse events (SAEs) continued until the final visit—30 days after the booster dose at 12 months. <jats:bold>Results</jats:bold> . At 30 days after the booster dose (12 months), the proportion of participants with seroprotection (hSBA ≥ 1:8) in the MenACWY-TT group was 89.6 % (serogroup A), 82.3 % (C), and 80.2 % (Y and W); in post-hoc analysis excluding one center (at which significantly different values were recorded compared to other sites) – ≥ 93.8 % for all serogroups. After the primary series (at 6 months), serological response was achieved in 70.1–94.8 % of participants. The immunogenicity of routine vaccines when co-administered was comparable to the comparator group. Local reactions to MenACWY-TT (erythema 7.4 %, tenderness 6.0 %) were mild or moderate in severity. Serious adverse events (SAEs) were reported in 2.7 % of participants in both groups, with no established relationship to vaccination. <jats:bold>Conclusion</jats:bold> . The MenACWY-TT vaccine administered according to a 2+1 schedule from the first months of life demonstrated good immunogenicity and a favorable safety profile when co-administered with pediatric vaccines of the National Immunization Schedule for routine immunization of infants. </jats:p>