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

Johannes Gutenberg-University
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 07/2012; 8(7):866-72. DOI: 10.4161/hv.20229
Source: PubMed


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 NCT00126984.

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    • "The results of our study using the GSK rSBA are consistent with other studies of MenACWY-TT persistence in adolescents and children where the same assay was employed [12] [13] [14]. Good antibody persistence up until 3 years after vaccination of adolescents with MenACWY-TT has been demonstrated, while in toddlers, persisting antibody levels have been observed to be similar or higher than after vaccination with licensed MenC-CRM 197 [13] [14] [15] [16] [17]. "
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    ABSTRACT: Long term protection against invasive meningococcal disease relies on persistence of bactericidal antibodies. We studied the persistence of serum bactericidal antibodies using rabbit and human complement (rSBA, hSBA assays) two years after vaccination with a meningococcal serogroup A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT, N = 253) or a licensed monovalent serogroup C conjugate vaccine (MenC-CRM197, N = 42) in Finnish toddlers who were aged 12–23 months at the time of vaccination. In 97.8–98.9% of subjects receiving MenACWY-TT, rSBA titres ⩾1:8 persisted against serogroups A, W and Y and 88.2% against serogroup C, which was according to exploratory analysis statistically significantly higher than in recipients of the MenC-CRM197 vaccine (69.0%). A total of 86.9% of subjects had persisting hSBA ⩾1:8 for serogroup C, which was statistically significantly higher than the MenC-CRM group (52.6%). Exploratory analysis also showed that the year 2 hSBA-MenC geometric mean titre was statistically significantly higher in the MenACWY-TT group than the MenC-CRM group. At least 87.0% of subjects had hSBA ⩾1:8 for serogroups W and Y at year 2, while the percentage was 23.0% for serogroup A. Using rSBA, but not hSBA, a high percentage of MenC-CRM197 recipients acquired antibody against serogroups A (82.1%), W (58.6%) and Y (80.0%). MenACWY-TT induced high level of bactericidal antibody in toddlers that persisted for at least 2 years.
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