title: Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial.
abstract: BACKGROUND
  Recent reviews have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines.
  
  
  OBJECTIVE
  To evaluate immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix, GlaxoSmithKline Biologicals) and DTPa-IPV-Hib (Pediacel, Sanofi Pasteur MSD) when coadministered as a 3-dose primary vaccination course.
  
  
  METHODS
  In a single-blind, single-center, randomized controlled trial in the Netherlands, healthy infants (n = 780) were randomly assigned (1:1:1) to receive either (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix Hexa, GlaxoSmithKline Biologicals), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (Prevenar/Prevnar, Pfizer Inc.) + DTPa-IPV-Hib at 2, 3, and 4 months of age. Blood samples were collected 1 month after dose 3. Diary cards were used to record safety and reactogenicity.
  
  
  RESULTS
  Antibody concentrations elicited by PHiD-CV coadministered with DTPa-IPV-Hib were noninferior to those following DTPa-HBV-IPV/Hib coadministration for 9 of 10 vaccines pneumococcal serotypes and protein D. For serotype 18C (conjugated to tetanus toxoid), the antibody concentration was higher with DTPa-HBV-IPV/Hib coadministration (1.73 vs. 1.07 μg/mL). The percentages of infants with antibody concentrations ≥0.2 μg/mL (68.9%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 64.9%-100% in the PHiD-CV + DTPa-IPV-Hib group) and with measurable opsonophagocytic activity (56.1%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 61.1%-100% in the PHiD-CV + DTPa-IPV-Hib group) were comparable for all serotypes in both PHiD-CV groups. Group differences in antibody responses to the DTPa-IPV-Hib antigens remained within the predefined limit for noninferiority. Safety and reactogenicity profiles were comparable across groups.
  
  
  CONCLUSIONS
  : PHiD-CV and DTPa-IPV-Hib were immunogenic and well tolerated when coadministered as a 3-dose primary vaccination course.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. mvandenbergh@spaarneziekenhuis.nl
authors.forename: Menno R
authors.initials: MR
authors.lastname: van den Bergh
authors.forename: Judith
authors.initials: J
authors.lastname: Spijkerman
authors.forename: Nancy
authors.initials: N
authors.lastname: François
authors.forename: Kristien
authors.initials: K
authors.lastname: Swinnen
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007072:Immunoglobulin D / Q000276:immunology*; D007223:Infant; D008074:Lipoproteins / Q000276:immunology*; D009426:Netherlands; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014611:Vaccination; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate
chemical_list: C538863:10-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D001426:Bacterial Proteins; D002352:Carrier Proteins; C513012:DTP-IPV-Hib vaccine; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D007072:Immunoglobulin D; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C067989:glpQ protein, Haemophilus influenzae