Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III, randomized study

• Published in: Vaccine Vol. 36; no. 31; pp. 4750 - 4758
• Main Authors: Rivera, Luis, Schwarz, Tino F., Kim, Kyung-Hyo, Kim, Yun-Kyung, Behre, Ulrich, Cha, Sung-Ho, Jo, Dae Sun, Lee, Jacob, Lee, Jin-Soo, Cheuvart, Brigitte, Jastorff, Archana, Van der Wielen, Marie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 25-07-2018; Elsevier Limited
• Subjects: Adolescents; Adults; Age; Antigens; Co-administration; Combined diphtheria-tetanus-acellular pertussis vaccine; Combined vaccines; Diphtheria; Epidemiology; Hemagglutinins; Immune response; Immunoassays; Immunogenicity; Pertussis; Pertussis toxin; Proteins; Quadrivalent meningococcal conjugate vaccine; Randomization; Safety; Teenagers; Tetanus; Toxins; Vaccines; Whooping cough; Young adults; South Korea; United States > US; Europe; Africa; Dominican Republic; Australia; Germany; LL; MMRV; TVC; NOCI; D; PT; MenW; MenY; PRN; T; rSBA; Tdap; Quadrivalent meningococcal conjugate vaccine; Lf; Combined diphtheria-tetanus-acellular pertussis vaccine; Safety; Tdap-HBV-IPV/Hib; GMC; HibMenCY-TT; Co-administration; IMD; AE; CI; MenACWY-TT; MenC; IU; GMT; MenA; Immunogenicity; SAE; ATP; FHA; ELISA
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.04.034

•We evaluated the co-administration of MenACWY-TT and Tdap in 11–25-year-olds.•Co-administration did not impact immune response to MenACWY-TT, diphtheria, tetanus.•Anti-pertussis antibody concentrations seemed lower following co-administration.•Robust post-Tdap anti-pertussis booster responses were observed in all groups.•Both vaccines had a clinically acceptable safety profile in both groups.
This study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults.
In this phase III, randomized, partially-blind study (NCT01767376), healthy 11–25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated.
Non-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles.
Immune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents.