A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial

Arch Dis Child. 2008 Nov;93(11):963-70. doi: 10.1136/adc.2007.136036. Epub 2008 May 7.

Abstract

Objective: To 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).

Design: A phase 3 open randomised controlled trial.

Setting: One centre in Oxford, UK and nine centres in Poland.

Subjects: 12-15-month-old healthy children.

Interventions: In 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 measures: The proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose.

Results: The 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).

Conclusion: The 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 number: NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / biosynthesis
  • Female
  • Haemophilus Infections / prevention & control
  • Haemophilus Vaccines / adverse effects
  • Haemophilus Vaccines / immunology*
  • Haemophilus influenzae type b / immunology
  • Humans
  • Immunization Schedule
  • Immunization, Secondary* / adverse effects
  • Infant
  • Male
  • Measles-Mumps-Rubella Vaccine / adverse effects
  • Measles-Mumps-Rubella Vaccine / immunology
  • Meningitis, Meningococcal / prevention & control
  • Neisseria meningitidis, Serogroup C / immunology
  • Poland
  • Tetanus Toxoid / adverse effects
  • Tetanus Toxoid / immunology*
  • United Kingdom
  • Vaccines, Conjugate / adverse effects
  • Vaccines, Conjugate / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Haemophilus Vaccines
  • Hib-MenCY-TT vaccine
  • Measles-Mumps-Rubella Vaccine
  • Tetanus Toxoid
  • Vaccines, Conjugate

Associated data

  • ClinicalTrials.gov/NCT00258700