title: Safety and immunogenicity of a hexavalent vaccine administered at 2, 4 and 6 months of age with or without a heptavalent pneumococcal conjugate vaccine: a randomized, open-label study.
abstract: BACKGROUND
  DTaP₅-IPV-Hib-HepB, an investigational hexavalent combination vaccine, was evaluated for safety and immunogenicity, when administered to infants with heptavalent pneumococcal conjugate vaccine (PCV7).
  
  
  METHODS
  Infants were randomized to receive DTaP₅-IPV-Hib-HepB plus PCV7, DTaP₅-IPV-Hib-HepB with PCV7 administered 1 month later or DTaP₅-IPV/Hib plus HepB plus PCV7 at 2, 4 and 6 months of age in an open-label, phase IIb trial. Vaccine responses were assessed by pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2/3 seroconversion rates, Haemophilus influenzae type b polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3 seroprotection rates and geometric mean titers. Solicited injection site and systemic reactions, serious adverse events, and other safety outcomes were reported.
  
  
  RESULTS
  Seroprotection rates to polyribosylribitol phosphate, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens across all groups met or exceeded predetermined acceptability criteria. Seroconversion rates to pertussis toxoid, pertactin and fimbriae types 2/3, but not filamentous hemagglutinin, met such criteria. Antidiphtheria antibodies were significantly lower when PCV7 was coadministered. Geometric mean titers to the other antigens of the hexavalent and PCV7 vaccines were all high and similar in the 2 groups. No safety signals were noted.
  
  
  CONCLUSIONS
  DTaP₅-IPV-Hib-HepB administered at 2, 4 and 6 months of age concomitantly with PCV7 was well tolerated and elicited robust antibody responses to all but the antidiphtheria antigens for which there may be evidence of immune interference. Only filamentous hemagglutinin did not meet seroconversion rate acceptability criteria.
authors.affiliation: Pediatric Infectious Diseases Division, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada. b.tapiero@umontreal.ca
authors.forename: Bruce
authors.initials: B
authors.lastname: Tapiéro
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Mark
authors.initials: M
authors.lastname: Dionne
authors.forename: William
authors.initials: W
authors.lastname: Meekison
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: Paul
authors.initials: P
authors.lastname: Zickler
authors.forename: Earl
authors.initials: E
authors.lastname: Rubin
authors.forename: Joanne
authors.initials: J
authors.lastname: Embree
authors.forename: Prakash
authors.initials: P
authors.lastname: Bhuyan
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lee
authors.forename: Minran
authors.initials: M
authors.lastname: Li
authors.forename: Antigona
authors.initials: A
authors.lastname: Tomovici
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine