title: Safety and immunogenicity of 2 mixed primary infant immunization schedules of pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, and Haemophilus influenzae Type B vaccines at 2, 4, and 6 months of age: a randomized controlled trial.
abstract: BACKGROUND
  Two pentavalent infant vaccines that contain either 5 or 3 component acellular pertussis antigens are authorized in Canada. Because of changes in vaccine use by provinces over time and movement of families across jurisdictions, it is possible that children are exposed to different combination vaccines during the primary infant immunization schedule. The safety and immunogenicity of mixed primary infant schedules is unknown.
  
  
  METHODS
  In a double-blind multicenter trial, 2-month-old healthy infants were randomized to 1 of 2 schedules at 2, 4, and 6 months of age (either Pediacel, Pediacel, Infanrix [PPI] or Infanrix, Pediacel, Pediacel [IPP]). Solicited local and systemic adverse events (AEs) were collected by parent diary on days 0 through 7; unsolicited AEs were collected for 31 days after each dose. Immune responses to polypolyribosylribitol phosphate capsular polysaccharide (PRP) (Haemophilus influenzae type b) and pertussis antigens were assessed before the first dose and 28 days after the 6 month (third) dose.
  
  
  RESULTS
  In all, 127 infants were randomized to IPP and 126 to PPI. The percentage of children with anti-PRP responses ≥0.15 μg/mL after dose 3 was higher in the IPP than in the PPI group (98.3, 95% CI: 94.1, 99.8 vs. 86.1%, 95% CI: 78.6, 91.7, P < 0.001). Antipertussis toxin and anti-fimbriae 2 and 3 responses were statistically significantly higher in the IPP than in the PPI group. Higher filamentous hemagglutinin responses occurred in PPI than in IPP. No difference between groups was observed in pertactin responses.Systemic AEs were similar between the 2 vaccine schedules. Irritability (67.2 vs. 51.6, P = 0.014) and mild crying (35.2% vs. 23.0%, P = 0.037) were more common after the 6-month dose in the PPI compared with the IPP group, as were overall systemic reactions (any intensity) for the PPI group after this dose (80.0 vs. 68.0, P = 0.042).
  
  
  CONCLUSIONS
  Mixed 2-, 4-, 6-month pentavalent infant vaccine schedules had different immunogenicity and reactogenicity, with a PPI schedule being more reactogenic, and less immunogenic for PRP and fimbriae 2 and 3 antigens at 7 months. It is preferable to complete the primary infant 3-dose vaccine series with the same vaccine, rather than considering infant vaccines as interchangeable.
authors.affiliation: Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre and Capital Health, Halifax, Canada. jmlangle@dal.ca
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Earl
authors.initials: E
authors.lastname: Rubin
authors.forename: Craig
authors.initials: C
authors.lastname: White
authors.forename: Shelly
authors.initials: S
authors.lastname: McNeil
authors.forename: Jill
authors.initials: J
authors.lastname: Mutch
authors.forename: Donna
authors.initials: D
authors.lastname: Mackinnon-Cameron
authors.forename: Bruce
authors.initials: B
authors.lastname: Smith
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D002170:Canada; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D011054:Poliovirus Vaccine, Inactivated; D018074:Vaccines, Conjugate; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine