Robin Marlow1, Sherine Kuriyakose2, Narcisa Mesaros3, Htay Htay Han4, Richard Tomlinson5, Saul N Faust6, Matthew D Snape7, Andrew J Pollard8, Adam Finn9. 1. Bristol Children's Vaccine Centre, University of Bristol, Upper Maudlin Street, Bristol BS2 8AE, UK. Electronic address: Robin.Marlow@bristol.ac.uk. 2. GSK, 5 Embassy Links, Cunningham Road, Bangalore 560052, India. Electronic address: sherine.o.kuriyakose@gsk.com. 3. GSK, 20 Avenue Fleming, Wavre 1300, Belgium. Electronic address: narcisa.x.mesaros@gsk.com. 4. GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406, United States. Electronic address: hhhlatt@hotmail.com. 5. Royal Devon & Exeter NHS Trust, Exeter EX2 5DW, UK. Electronic address: Richard.tomlinson@nhs.net. 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: s.faust@soton.ac.uk. 7. Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Headington, Oxford OX3 9DU, UK. Electronic address: matthew.snape@paediatrics.ox.ac.uk. 8. Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Headington, Oxford OX3 9DU, UK. Electronic address: andrew.pollard@paediatrics.ox.ac.uk. 9. Bristol Children's Vaccine Centre, University of Bristol, Upper Maudlin Street, Bristol BS2 8AE, UK.
Abstract
AIM: To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPVB) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPVR (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-IPVB or dTap-IPVR) 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-IPVB 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-IPVB group and 130 in the dTap-IPVR 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-IPVB group. CONCLUSION: Non-inferiority of dTap-IPVB to dTap-IPVR 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).
RCT Entities:
AIM: To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPVB) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPVR (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-IPVB or dTap-IPVR) 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-IPVB 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-IPVB group and 130 in the dTap-IPVR 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-IPVB group. CONCLUSION: Non-inferiority of dTap-IPVB to dTap-IPVR 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).
Authors: H J Zar; D P Moore; S Andronikou; A C Argent; T Avenant; C Cohen; R J Green; G Itzikowitz; P Jeena; R Masekela; M P Nicol; A Pillay; G Reubenson; S A Madhi Journal: Afr J Thorac Crit Care Med Date: 2020-10-13