Randomized clinical trial of DTaP5-HB-IPV-Hib vaccine administered concomitantly with meningococcal serogroup C conjugate vaccines during the primary infant series

Jennifer L. Oliver, Christine Sadorge, Florence Boisnard, Matthew D. Snape, Richard Tomlinson, Rebecca Mann, Peter Rudd, Shyam Bhakthavalsala, Saul N. Faust, Paul T. Heath, Stephen M. Hughes, Raymond Borrow, Stéphane Thomas, Adam Finn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Concomitant administration of vaccines simplifies delivery. DTaP5-HB-IPV-Hib is a fully liquid, combination vaccine against 6 diseases. This study evaluated the compatibility of DTaP5-HB-IPV-Hib with 2 different meningococcus group C conjugate (MCC) vaccines in infants. Methods: In a phase 3, open-label study, 284 healthy infants from 11 UK centres received DTaP5-HB-IPV-Hib at age 2, 3, and 4 months; 13-valent pneumococcal conjugate vaccine (PCV13) at 2 and 4 months; a Haemophilus influenzae type b (Hib)-MCC vaccine and a measles/mumps/rubella vaccine at 12 months. Participants were randomised 1:1 to receive either an MCC-detoxified tetanus toxin vaccine (MCC-TT; n = 141) or an MCC-Corynebacterium diphtheriae CRM197 protein vaccine (MCC-CRM; n = 143) at 3 and 4 months. The primary outcome was seroprotection rate (SPR) to MCC (percent with rabbit complement serum bactericidal antibody titer ≥8). Results: Per protocol analysis, MCC SPRs were 100 and 96.4 one month after the first dose, 100 and 99.1 after the second dose, and 100 and 97.3 after the third (booster) dose of MCC in the MCC-TT and MCC-CRM groups, respectively. One month after all 3 doses of DTaP5-HB-IPV-Hib, immunoglobulin G anti-polyribosylribitol phosphate SPRs (% ≥0.15 µg/mL) were 97.8 in the MCC-TT group and 100 in the MCC-CRM group; anti-hepatitis B antigen SPRs (% ≥10 mIU/mL) were 96.8 and 96.3 in the MCC-TT and MCC-CRM groups, respectively. All participants were seroprotected against diphtheria and tetanus (≥0.01 IU/mL) and poliovirus types 1, 2, and 3 (≥8 dilution), and seroresponse rates to all pertussis antigens were ≥90.4%. Two vaccine-related serious adverse events (transient severe abdominal pain and crying) occurred concomitantly in 1 participant in the MCC-CRM group. Adverse event rates were similar to other studies of DTaP5-HB-IPV-Hib, with pyrexia ≥38 °C in 10.9% of participants following any dose. Conclusions: DTaP5-HB-IPV-Hib can be effectively used in a 2-, 3-, and 4-month infant priming schedule when given with 2 doses of MCC.

Original languageEnglish
Pages (from-to)5718-5725
Number of pages8
JournalVaccine
Volume38
Issue number35
DOIs
Publication statusPublished - 31 Jul 2020

Bibliographical note

Funding Information:
Jennifer L Oliver received a grant for manuscript preparation from Sanofi Pasteur MSD. Christine Sadorge : was an employee of Sanofi Pasteur MSD at the time the study was conducted. Florence Boisnard was an employee of Sanofi Pasteur MSD at the time the study was conducted. Matthew D Snape reports a grant for conducting this study from Sanofi-Pasteur; and grants for conducting other studies from GlaxoSmithKline, Janssen, Medimmune, Novavax, MCM, and Pfizer. Richard Tomlinson reports that his institution received grants for conducting this study from Sanofi Pasteur MSD. Rebecca Mann reports that her institution received grants for conducting this study from Sanofi Pasteur MSD. Peter Rudd reports that his institution received grants for conducting this study from Sanofi Pasteur MSD. Shyam Bhakthavalsala reports that his institution received grants for conducting this study from Sanofi Pasteur MSD. Saul Faust reports that his institution received grants for conducting this study from Sanofi Pasteur MSD and for conducting other studies from Pfizer, Sanofi, GSK, Novartis, Alios, J&J, and Merck; and his institution received fees for participating as a symposium speaker from Pfizer, and for advisory board participation from AstraZeneca/MedImmune, Sanofi, Pfizer, Sequerius, Sandoz, and Merck. Paul Heath reports that his institution received a grant for conducting this study from Sanofi Pasteur MSD and grants for conducting other studies from GlaxoSmithKline, Janssen, Medimmune, Novavax, and Pfizer. Stephen Hughes has received fees for advisory board participation from Sanofi. Ray Borrow performs contract research on behalf of Public Health England for GSK, Pfizer and Sanofi Pasteur. Stephane Thomas was an employee of Sanofi Pasteur MSD at the time the study was conducted. Adam Finn reports that his institution received grants for conducting this study from Sanofi Pasteur MSD and for conducting other studies from GSK.

Funding Information:
The authors take full responsibility for the content of this manuscript. The authors would like to thank the participants who took part in the trial; Paul Heaton, BM, DCH, MRCP, FRCPCH, of Yeovil Hospital, Somerset, UK, and Andrew Collinson, MBChB, MD, of the Royal Cornwall Hospitals NHS Trust, Truro, UK, for their contributions to the conduct of the study. A thank you also goes to the NIHR Local Clinical Research Networks (South London, Thames Valley, Western and Wessex), the NIHR Oxford Biomedical Research Centre and NIHR Southampton Clinical Research Facility, and the NIHR Southampton Biomedical Research Centre. Medical writing and editorial support were provided by Meredith Rogers, MS, CMPP, of the Lockwood Group, Stamford, CT, USA. This assistance was funded by MCM Vaccine B.V. Leiden, The Netherlands, a partnership between Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA, and Sanofi Pasteur, Inc. Swiftwater, PA, USA. This study was sponsored by MCM Vaccine B.V. Leiden, The Netherlands, a partnership between Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA, and Sanofi Pasteur, Inc. Swiftwater, PA, USA.

Funding Information:
This study was sponsored by MCM Vaccine B.V., Leiden, The Netherlands, a partnership between Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Sanofi Pasteur, Inc., Swiftwater, PA, USA.

Publisher Copyright:
© 2020

Keywords

  • Antigen
  • Children
  • Combination
  • Immunization
  • Meningococcus
  • Vaccine

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