title: Immunogenicity and safety of an investigational fully liquid hexavalent combination vaccine versus licensed combination vaccines at 6, 10, and 14 weeks of age in healthy South African infants.
abstract: BACKGROUND
  Assessment of primary vaccination of a new fully liquid, hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) in South African infants.
  
  
  METHODS
  Infants were randomized to the following at 6, 10, and 14 weeks of age (Expanded Program on Immunization schedule): DTaP-IPV-Hep B-PRP-T (Group 1; N = 286); DTwP-Hib, hepatitis B, and OPV vaccines (Group 2; N = 286); or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth (Group 3; N = 143). Antibody titers were measured before vaccination (pertussis toxoid, filamentous hemagglutinin) and postprimary vaccination (all valences). Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates. Safety was evaluated from parental reports.
  
  
  RESULTS
  Noninferiority (Group 1 minus Group 2) was demonstrated for anti-HBs, -PRP, -diphtheria, -tetanus, and -polio 1, 2, 3 (lower 95% confidence interval for the difference was -8.20 to 3.46). Anti-HBs antibody titers ≥10 mIU/mL and anti-PRP ≥0.15 μg/mL were ≥95.4% in each group. Seroprotection rates were also high for the other antigens. Seroconversion rates (4-fold increase from pre- to postvaccination) were 93.6%, 83.2%, and 95.1% in Groups 1, 2, and 3, respectively, for anti-pertussis toxoid and 93.1%, 57.7%, and 90.0% for anti-filamentous hemagglutinin. Anti-HBs GMTs were 330, 148, and 1913 mIU/mL for Groups 1, 2, and 3, respectively. Reactogenicity was similar in each group. Fever ≥39.0°C occurred in 1.7%, 0.4%, and 0.0% of infants in Groups 1, 2, and 3, respectively; no extensive limb swelling, hypotonic-hyporesponsive episodes, or vaccine-related serious adverse events were reported.
  
  
  CONCLUSIONS
  The new, fully liquid, investigational hexavalent vaccine in the Expanded Program on Immunization schedule, with/without hepatitis B at birth, is highly immunogenic and safe compared with control vaccines, warranting further development.
authors.affiliation: Department of Science, University of the Witwatersrand, Johannesburg, Republic of South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Ismail
authors.initials: I
authors.lastname: Mitha
authors.forename: Clare
authors.initials: C
authors.lastname: Cutland
authors.forename: Michelle
authors.initials: M
authors.lastname: Groome
authors.forename: Eduardo
authors.initials: E
authors.lastname: Santos-Lima
mesh_terms: D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / 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*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D023321:Poliovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D013019:South Africa; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D023321:Poliovirus Vaccines; D017778:Vaccines, Combined