A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial
- D Pace1,
- M Snape1,
- S Westcar1,
- C Oluwalana1,
- L-M Yu2,
- N Begg3,
- J Wysocki4,
- H Czajka5,
- G Maechler3,
- D Boutriau3,
- A J Pollard1
- 1Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford, UK
- 2Centre for Statistics in Medicine, Wolfson College Annexe, University of Oxford, Linton Road, Oxford, UK
- 3GlaxoSmithKline Biologicals, Rixensart, Belgium
- 4Department of Preventive Medicine, Poznan University of Medical Sciences and Specialist Team of Care over Mother and Child, Dispensary Medicine of Development Age, Poznan, Poland
- 5Cracow Specialist Hospital, under the name of John Paul II, Vaccination Centre, Krakow, Poland
- David Pace, Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, UK;
- Accepted 28 April 2008
- Published Online First 7 May 2008
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 ⩾1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations ⩾1.0 μg/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).
Funding: This study (study ID: 103974; Clinical Trial Register Number NCT00258700 (www.clinicaltrials.gov)) was sponsored by GlaxoSmithKline Biologicals, Rixensart, Belgium. The Oxford Vaccine Group is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. AJP is a Jenner Institute Investigator.
Competing interests: AJP has conducted clinical trials on behalf of Oxford University and organised international conferences, sponsored by the following vaccine manufacturers: Wyeth Vaccines, GlaxoSmithKline Vaccines, Sanofi Pasteur, Sanofi Pasteur MSD and Novartis Vaccines. Industry-sourced honoraria for consultancy, lecturing or writing and travel assistance are paid directly to an independent charity or an educational/administrative fund held by the Department of Paediatrics, University of Oxford. MDS has received assistance to attend scientific meetings from Novartis Vaccines. DP has received travel grants from the company that sponsored the study and from Wyeth to attend scientific meetings. JW and HC received travel grants from the company that sponsored the study. NB and DB have stock ownership and DB is an inventor of patent applications. The other authors have no conflict of interest.
Ethics approval: The study was approved by the Oxfordshire Research Ethics Committee in the UK and by the Bioethics Committee at the Regional Medical Council of the Regional Wielkopolska Chamber of Physicians and Dentists in Poznan, Poland.
Contributors: HC, CO, DP, AJP, MS, SW, JW and L-MY declare they have been involved in the study design, acquisition or analysis and interpretation of data, draft/critical revision of the article and final approval of the version to be published. AJP acts as a guarantor for the overall content of the article. DB and GM declare they have been involved in the study conception and design, acquisition or analysis and interpretation of data, draft/critical revision of the article and final approval of the version to be published. NB declares he has been involved in the study conception and design, draft/critical revision of the article and final approval of the version to be published.
Statement of independence of researchers from funders: The University of Oxford received and managed the budget from the funder, GlaxoSmithKline Biologicals, to conduct the clinical trial and no payments were made to Drs Oluwalana, Pace, Pollard, Snape, Westcar or Yu by GlaxoSmithKline Biologicals. NB, DB and GM are employees of GlaxoSmithKline Biologicals. JW received and managed the budget from the funder, GlaxoSmithKline Biologicals, to conduct the clinical trial and no payments were made to his institute. HC received and managed the budget from the funder, GlaxoSmithKline Biologicals, to conduct the clinical trial and her institute was paid by the funder, GlaxoSmithKline Biologicals.
Infanrix-IPV, Menitorix and Priorix are trademarks of the GlaxoSmithKline group of companies, Pediacel is the trademark of Sanofi Pasteur and Meningitec is the trademark of Wyeth Vaccines.