Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study

Abstract

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Keywords: Coadministration; MenACYW-TT; paediatric vaccines; toddlers.

Fig. 1.

Proportion of participants with (a) hSBA meningococcal titres ≥1:8, (b) anti-measles antibody concentrations ≥225 mIU/ml, (c) anti-mumps antibody concentrations ≥10 mumps antibody units/ml, (d) anti-rubella concentrations ≥10 IU/ml and (e) anti-varicella antibody concentrations ≥5 glycoprotein ELISA antibody units/ml at Day 30 in participants randomised to MenACYW-TT + MMR + V, MenACYW-TT and MMR + V (PPAS). ELISA, enzyme-linked immunosorbent assay; hSBA, serum bactericidal antibody assay using human complement; MMR, measles, mumps and rubella vaccine; PPAS, per-protocol analysis set; V, varicella vaccine.

Fig. 2.

Proportion of participants with (a) hSBA meningococcal titres ≥1:8, (b) anti-tetanus antibody concentrations ≥0.1 and 1.0 IU/ml, (c) anti-diphtheria antibody concentrations ≥0.1 and 1.0 IU/ml, (d) anti-pertussis PT and FHA vaccine response*, (e) anti-polio 1, 2 and 3 antibody titres ≥1:8, (f) anti-Hep B antibody concentrations ≥10 and 100 mIU/ml, and (g) anti-PRP antibody concentrations ≥0.15 and 1.0 μg/ml at Day 30 in participants randomised to MenACYW-TT + DTaP-IPV-HepB-Hib, MenACYW-TT and DTaP-IPV-HepB-Hib (PPAS). DTaP-IPV-HepB-Hib, diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b vaccine; FHA, filamentous haemagglutinin; hSBA, serum bactericidal antibody assay using human complement; PPAS, per-protocol analysis set; PRP, polyribosyl-ribitol phosphate; PT, pertussis toxoid.

Fig. 3.

Proportion of participants with (a) hSBA meningococcal titres ≥1:8, and anti-pneumococcal antibody concentrations (b) ≥0.35 μg/ml and (c) ≥1.0 μg/ml to serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F at Day 30 in participants randomised to MenACYW-TT + PCV13, MenACYW-TT and PCV13 (PPAS). hSBA, serum bactericidal antibody assay using human complement; PCV13, pneumococcal conjugate vaccine; PPAS, per-protocol analysis set.