Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

Abstract

Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR).

Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines.

Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations.

Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

Keywords: conjugate vaccine; immunogenicity; infants; meningococcal disease; safety.

Figure 1. Subject disposition flowchart. *Routine vaccines at 2, 4, and 6 mo visits included DTaP-IPV/Hib, HBV, and either PCV-7 or PCV-13. ^†Routine vaccines at 12 mo visit included MMR and either PCV-7 or PCV-13.

Figure 2. (A) Percentage of participants (95% CI) in MenACWY-CRM + Routine (left) and Routine Only (right) groups with hSBA titers ≥8 at baseline, 1-mo following the 3-dose infant series (7 mo) and prior to the toddler dose, at 12 mo, per serogroup. (B) Immunogenicity results after 4 doses of MenACWY-CRM. Percentage of participants (95% CI) with hSBA titers ≥8 at 1-mo after the 4th vaccination (13 mo) in MenACWY-CRM + Routine and Routine Only groups, per serogroup.* Dashed lines illustrate criterion for response sufficiency, i.e., LL95%CI ≥85% for serogroups C, W-135, and Y and ≥80% for serogroup A after 4 doses of MenACWY-CRM. (C) GMTs (95% CI) in MenACWY-CRM + Routine (left) and Routine only (right) groups before vaccination, 1-mo after the 3-dose infant series (7 mo), prior to toddler dose (12 mo), and 1-mo following toddler dose (13 mo), per serogroup.

Figure 3. Seroresponse in participants with and without MenACWY-CRM after routine vaccinations at 2, 4, 6, and 12 mo. The difference in percentage of seroresponders (95% CI) is shown. (A) Percentage of participants with seroresponse to concomitant vaccinations DTaP-IPV/Hib 1-mo after the 3-dose infant series, at 7 mo. (B) Percentage of participants with seroresponse to pneumococcal conjugate 1-mo after the 3-dose infant series, at 7 mo. (C) Percentage of participants with seroresponse to pneumococcal conjugate 1-mo after the 4th vaccine dose, at 13 mo. *Non-inferiority criteria met for the difference in percentage of seroresponders, i.e., LL95%CI ≥–5% for poliovirus and ≥–10% for all other antigens.