Quadrivalent meningococcal tetanus toxoid-conjugate booster vaccination in adolescents and adults: phase III randomized study

Abstract

Background: The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier.

Methods: This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study.

Results: The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported.

Conclusions: MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile.

Impact: A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.

Fig. 1. Participant disposition flow chart.

*subset cohort† one participant was withdrawn by parent and Day 30 visit not conducted due to COVID-19, two participants were lost to follow up and Day 30 visit not conducted due to COVID-19, and one participant was enrolled in error (previously vaccinated with another meningococcal vaccine)‡ Day 30 visit was not conducted (due to COVID-19 for 3/4 participants)¶ Day 30 visit was not conducted for one participant due to parental concern about COVID-19, and one participant was enrolled in error (previously vaccinated with another meningococcal vaccine).

Fig. 2. Proportion of participants with hSBA vaccine seroresponse at Day 6 post-MenACYW-TT booster.

Proportion of participants with hSBA vaccine seroresponse at Day 6 post-MenACYW-TT booster in MenACYW-TT primed (Group 1) and MCV4-CRM primed (Group 2) participants (PPAS1). Errors bars indicate 95% confidence intervals. Group 1, MenACYW-TT primed: MenACYW-TT booster; Group 2, MCV4-CRM primed: MenACYW-TT booster. *For a participant with a pre-vaccination titer <1:8, the post-vaccination titer must be ≥1:16; for a participant with a pre-vaccination titer ≥1:8, the post-vaccination titer must be at least 4-fold greater than the pre-vaccination titer

Fig. 3. Persistence of hSBA GMTs following priming vaccination with MenACYW-TT or MCV4-CRM.

Persistence of hSBA GMTs to serogroup A (a), serogroup C (b), serogroup W (c) and serogroup Y (d) following priming vaccination with MenACYW-TT or MCV4-CRM (FAS3). CI, confidence interval; GMT, geometric mean titer; N, total subjects; hSBA human complement serum bactericidal antibody assay. MenACYW-TT primed (red line), Group 1, 3 and 4 participants who were MenACYW-TT primed in the previous studies, MET50 or MET43; MCV4-CRM primed (blue line), Group 2 participants who were MCV4-CRM primed in the previous study, MET50.

Fig. 4. Percentage of subjects achieving hSBA vaccine seroresponse at Day 30 post-booster with MenACYW-TT booster alone, or co-administered with MenB-T or 4CMenB.

Errors bars indicate 95% confidence intervals. hSBA, human complement serum bactericidal antibody assay Group 1, MenACYW-TT primed: MenACYW-TT booster; Group 3, MenACYW-TT primed: MenACYW-TT booster +MenB-T; Group 4, MenACYW-TT primed: MenACYW-TT booster +4CMenB *For a participant with a pre-vaccination titer <1:8, the post-vaccination titer must be ≥1:16; for a participant with a pre-vaccination titer ≥1:8, the post-vaccination titer must be at least 4-fold greater than the pre-vaccination titer