title: Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.
abstract: Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse events were reported. In conclusion, Tdap vaccination 3-4weeks before concomitant administration of PCV13 and MCV4 significantly reduced the antibody response to six of the 13 pneumococcal serotypes in adults. The trial is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000536763.
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, NSW, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia. Electronic address: Mohamed.tashani@health.nsw.gov.au.
authors: M
authors: M
authors: Tashani
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, NSW, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Family and Community Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: M
authors: M
authors: Alfelali
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, NSW, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; The Executive Administration of Research, King Abdullah Medical City (KAMC), Makkah, Saudi Arabia.
authors: O
authors: O
authors: Barasheed
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; School of Public Health, The University of Sydney, Sydney, NSW, Australia.
authors: A S
authors: AS
authors: Alqahtani
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Kids Research Institute, The Children's Hospital at Westmead, NSW, Australia.
authors: L
authors: L
authors: Heron
authors: Immunology Department, The Children's Hospital at Westmead, Westmead 2145, NSW, Australia.
authors: M
authors: M
authors: Wong
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, NSW, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia.
authors: H
authors: H
authors: Rashid
authors: National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, NSW, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia; WHO Collaborating Centre for Mass Gatherings and High Consequence/High Visibility Events, Flinders University, Adelaide 5001, Australia.
authors: R
authors: R
authors: Booy
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001315:Australia; D003017:Clostridium tetani / Q000276:immunology*; D003353:Corynebacterium diphtheriae / Q000276:immunology*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007514:Islam; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008875:Middle Aged; D009895:Opsonin Proteins; D010587:Phagocytosis; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D014195:Travel; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D022401:Meningococcal Vaccines; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines
keywords: Carrier interference; Diphtheria and acellular pertussis vaccine; Pneumococcal conjugate vaccine; Pneumococcal opsonophagocytic assay