A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK

Robin Marlow; Sherine Kuriyakose; Narcisa Mesaros; Htay Htay Han; Richard Tomlinson; Saul N Faust; Matthew D Snape; Andrew J Pollard; Adam Finn

doi:10.1016/j.vaccine.2018.03.021

A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK

Vaccine. 2018 Apr 19;36(17):2300-2306. doi: 10.1016/j.vaccine.2018.03.021. Epub 2018 Mar 22.

Authors

Robin Marlow¹, Sherine Kuriyakose², Narcisa Mesaros³, Htay Htay Han⁴, Richard Tomlinson⁵, Saul N Faust⁶, Matthew D Snape⁷, Andrew J Pollard⁸, Adam Finn⁹

Affiliations

¹ Bristol Children's Vaccine Centre, University of Bristol, Upper Maudlin Street, Bristol BS2 8AE, UK. Electronic address: [email protected].
² GSK, 5 Embassy Links, Cunningham Road, Bangalore 560052, India. Electronic address: [email protected].
³ GSK, 20 Avenue Fleming, Wavre 1300, Belgium. Electronic address: [email protected].
⁴ GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406, United States. Electronic address: [email protected].
⁵ Royal Devon & Exeter NHS Trust, Exeter EX2 5DW, UK. Electronic address: [email protected].
⁶ Southampton NIHR Wellcome Trust Clinical Research Facility and Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK. Electronic address: [email protected].
⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Headington, Oxford OX3 9DU, UK. Electronic address: [email protected].
⁸ Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Headington, Oxford OX3 9DU, UK. Electronic address: [email protected].
⁹ Bristol Children's Vaccine Centre, University of Bristol, Upper Maudlin Street, Bristol BS2 8AE, UK.

PMID: 29576304
DOI: 10.1016/j.vaccine.2018.03.021

Abstract

Aim: To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV_B) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV_R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV).

Methods: This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV_B or dTap-IPV_R) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV_B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated.

Results: 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV_B group and 130 in the dTap-IPV_R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV_B group.

Conclusion: Non-inferiority of dTap-IPV_B to dTap-IPV_R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old.

Trial registration: NCT01245049 (ClinicalTrials.gov).

Keywords: Child; Preschool booster; RCT; UK; dTap-IPV.

Publication types

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

MeSH terms

Antibodies, Bacterial / immunology
Antibodies, Viral / immunology
Antibody Formation / immunology*
Antigens / immunology*
Child, Preschool
Diphtheria / immunology
Diphtheria / prevention & control
Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
Diphtheria-Tetanus-Pertussis Vaccine / immunology*
Diphtheria-Tetanus-acellular Pertussis Vaccines / adverse effects
Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology
Female
Humans
Immunization, Secondary / adverse effects*
Male
Measles-Mumps-Rubella Vaccine / adverse effects*
Measles-Mumps-Rubella Vaccine / immunology*
Poliomyelitis / immunology
Poliomyelitis / prevention & control
Poliovirus / immunology
Poliovirus Vaccine, Inactivated / adverse effects*
Poliovirus Vaccine, Inactivated / immunology*
Tetanus / immunology
Tetanus / prevention & control
United Kingdom
Vaccination / methods
Vaccines, Combined / adverse effects
Vaccines, Combined / immunology
Whooping Cough / immunology
Whooping Cough / prevention & control

Substances

Antibodies, Bacterial
Antibodies, Viral
Antigens
DTPP vaccine
Diphtheria-Tetanus-Pertussis Vaccine
Diphtheria-Tetanus-acellular Pertussis Vaccines
Measles-Mumps-Rubella Vaccine
Poliovirus Vaccine, Inactivated
Vaccines, Combined

Associated data

ClinicalTrials.gov/NCT01245049