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

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 mu g/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). Conclusion: 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.