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

David Pace ^1*, Matthew D Snape ¹, Sharon Westcar ¹, Claire Oluwalana ¹, Ly-Mee Yu ¹, Norman Begg ², Jacek Wysocki ³, Hanna Czajka ⁴, Gudrun Maechler ², Dominique Boutriau ² and Andrew J Pollard ¹

¹ University of Oxford, United Kingdom
² GlaxoSmithKline, Biologicals, Belgium
³ Poznan University of Medical Sciences & Specialist Team of Care over Mother and Child, Dispensary Me, Poland
⁴ Cracow Specialist Hospital, under the name of John Paul II, Vaccination Centre, Krakow, Poland, Poland

^* To whom correspondence should be addressed. E-mail: dpace{at}mail.global.net.mt.

Accepted 28 April 2008

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 of 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 who were vaccinated with a combination of Hib-MenC-TT + DTPa-IPV or MenC-CRM197 + DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (LL 95%CI 92.4) of participants had rSBA-MenC 1:128 and 100% (LL 95%CI 99.2) achieved anti-PRP concentrations 1.0µg/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 a dose of 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: Clinical trials.gov, NCT00258700. Study ID: 103974.