Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults

Abstract

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

FIG. 1.

Flowchart of subjects enrolled.

FIG. 2.

Proportions of subjects achieving human serum bactericidal assay (hSBA) titers of ≥1:4 against Neisseria meningitidis serogroups A, C, W-135, and Y 1 month after vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) plus a combined tetanus, reduced diphtheria, and acellular pertussis vaccine (Tdap) or with MenACWY-CRM plus saline placebo (SP). Error bars represent 95% confidence intervals.

FIG. 3.

Proportions of subjects achieving antibody concentrations of ≥1.0 IU/ml against diphtheria and tetanus antigens 1 month after vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) plus a combined tetanus, reduced diphtheria, and acellular pertussis vaccine (Tdap) or vaccination with Tdap plus saline placebo (SP). Error bars represent 95% confidence intervals.

FIG. 4.

Proportion of subjects achieving a 4-fold increase in concentrations of antibodies against pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]) 1 month after vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) plus a combined tetanus, reduced diphtheria, and acellular pertussis vaccine (Tdap) or with Tdap plus saline placebo. The asterisk indicates noninferiority (the lower limit of the 95% confidence interval was ≥−10%). Error bars represent 95% confidence intervals.

FIG. 5.

Reverse cumulative distribution of anti-pertussis toxoid (anti-PT) (A), anti-filamentous hemagglutinin (anti-FHA) (B), and anti-pertactin (anti-PRN) (C) titers prevaccination and 1 month postvaccination. MenACWY-CRM, quadrivalent meningococcal conjugate vaccine; Tdap, combined tetanus, reduced diphtheria, and acellular pertussis vaccine.