Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children

Abstract

The present extension study, conducted in children originally vaccinated at 12-14 mo or 3-5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ≥ 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ≥ 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ≥ 1:8 and ≥ 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984.

Figures

Figure 1. Participant flow. ACWY_T, toddlers vaccinated with MenACWY-TT at 12–14 mo of age; MenCCRM, toddlers vaccinated with MenC-CRM197 at 12–14 mo of age; ACWY_C, children vaccinated with MenACWY-TT at 3–5 y of age; MenPS, children vaccinated with MenPS at 3–5 y of age; ATP, according to protocol; TVC, total vaccinated cohort; N, number of participants. 1Several formulations were evaluated in the primary study, but participants who received the selected formulation for further development or control vaccine were eligible to participate in the persistence study. Participants who withdrew from the primary phase were described in the previous publication.

Figure 2. Geometric mean titers for rSBA at pre-vaccination, at 1 mo and 15 mo after primary vaccination (ATP cohort for persistence) and at 1 mo after the polysaccharide challenge (ATP cohort for immune memory). Notes: ATP, according to protocol; ACWY_T, toddlers primed with MenACWY-TT at 12–14 mo of age; MenCCRM, toddlers primed with MenC-CRM197 at 12–14 mo of age; ACWY_C, children primed with MenACWY-TT at 3–5 y of age; MenPS, children primed with MenPS at 3–5 y of age; Errors bars, exact 95% confidence interval; Month 0, pre-primary vaccination; Month 1, 1 mo post-primary vaccination; Month 15, 15 mo post-primary vaccination; Month 16, one month post-polysaccharide challenge. 1These numbers are not the same as those presented in the previous publication at the same timepoints because the analyses for the present study were conducted on the ATP cohorts for persistence and immune memory (Month 15) and in the previous publication the analyses were performed on the ATP cohort for immunogenicity (Month 1). *Statistically significantly higher values compared with the control group (exploratory analysis)