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Randomized Controlled Trial Multicenter Study
A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial.
- D Pace, M Snape, S Westcar, C Oluwalana, L-M Yu, N Begg, J Wysocki, H Czajka, G Maechler, D Boutriau, and A J Pollard.
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford, UK. dpace@mail.global.net.mt
- Arch. Dis. Child. 2008 Nov 1;93(11):963-70.
ObjectiveTo study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR).DesignA phase 3 open randomised controlled trial.SettingOne centre in Oxford, UK and nine centres in Poland.Subjects12-15-month-old healthy children.InterventionsIn the primary stage of the study 500 healthy 6-12-week-old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT+DTPa-IPV or MenC-CRM197 vaccine+DTPa-IPV-Hib. In the booster stage, 476 participants (190 in the UK and 286 in Poland) were vaccinated with Hib-MenC-TT and MMR.Main Outcome MeasuresThe proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose.ResultsThe co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children vaccinated with Hib-MenC-TT+DTPa-IPV or MenC-CRM197+DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (lower limit of (LL) 95% CI 92.4) of participants had rSBA-MenC >or=1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations >or=1.0 microg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95% CI 6.2 to 19.4).ConclusionThe waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease.Trial Registration NumberNCT00258700. Study ID: 103974 (http://clinicaltrials.gov).
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