title: Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.
abstract: BACKGROUND
  : Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015.
  
  
  METHODS
  We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA).
  
  
  RESULTS
  A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P  <   0.05) lower geometric mean titres (GMTs) post-vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination.
  
  
  CONCLUSIONS
  Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the conjugate vaccine is recommended to avoid immune interference.
authors.affiliation: 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.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Tashani
authors.affiliation: 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.forename: Leon
authors.initials: L
authors.lastname: Heron
authors.affiliation: Department of Immunology, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.affiliation: 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.|Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Harunor
authors.initials: H
authors.lastname: Rashid
authors.affiliation: 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.|Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|WHO Collaborating Centre for Mass Gatherings and High Consequence/High Visibility Events, Flinders University, Adelaide, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012067:Religion; D057236:Travel Medicine; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage* / Q000276:immunology; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Hajj; Pneumococcal conjugate vaccine; carrier interference; carrier priming; pneumococcal opsonophagocytic assay