A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2-10 y.

University of Tampere
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 10/2012; 8(12). DOI: 10.4161/hv.22165
Source: PubMed


Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2-10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2-10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at NCT00427908.

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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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