title: Concomitant administration of a virosome-adjuvanted hepatitis a vaccine with routine childhood vaccines at age twelve to fifteen months: a randomized controlled trial.
abstract: BACKGROUND
  The objectives of this trial were to test for noninferiority of a virosomal hepatitis A virus (HAV) vaccine (Epaxal) coadministered with routine childhood vaccines compared with Epaxal given alone and to an alum-adjuvanted HAV vaccine (Havrix Junior) coadministered with routine childhood vaccines.
  
  
  METHODS
  Healthy children 12- to 15-month-old were randomized to receive either a pediatric dose (0.25 mL) of Epaxal coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 109; group A), or Epaxal given alone (n = 105; group B), or Havrix Junior coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 108; group C). A booster dose was given 6 months later. Anti-HAV antibodies were tested before and 1 month after each vaccination. Safety was assessed for 1 month after each vaccination. Solicited adverse events were assessed for 4 days after each vaccination.
  
  
  RESULTS
  : HAV seroprotection rates (> or =20 mIU/mL) at 1 and 6 months after first dose were: A: 94.2% and 87.5%, B: 92.6% and 80.0%, C: 78.2% and 71.3%, respectively (A versus C: P < 0.001 and P = 0.017 at month 1 and 6, respectively). The respective geometric mean concentrations were: A: 51 and 64 mIU/mL, B: 49 and 59 mIU/mL, C: 33 and 37 mIU/mL (A versus C: P < 0.001 at both time points). All groups achieved 100% seroprotection after the booster dose. The geometric mean concentrations after the booster dose were 1758, 1662, and 1414, for groups A, B and C, respectively (A versus C: P = 0.15). No clinically significant reduction in immune response to all concomitant vaccine antigens was seen. All vaccines were well tolerated.
  
  
  CONCLUSIONS
  : Coadministration of pediatric Epaxal with routine childhood vaccines showed immunogenicity and safety equal to Epaxal alone as well as to Havrix Junior. After first dose, Epaxal was significantly more immunogenic than Havrix Junior.
authors.affiliation: Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. rdagan@bgu.ac.il
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
authors.forename: Jacob
authors.initials: J
authors.lastname: Amir
authors.forename: Gilat
authors.initials: G
authors.lastname: Livni
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Jaber
authors.initials: J
authors.lastname: Abu-Abed
authors.forename: Lior
authors.initials: L
authors.lastname: Guy
authors.forename: Shai
authors.initials: S
authors.lastname: Ashkenazi
authors.forename: Gert
authors.initials: G
authors.lastname: Foresner
authors.forename: Gert
authors.initials: G
authors.lastname: Froesner
authors.forename: Friedemann
authors.initials: F
authors.lastname: Tewald
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Schätzl
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Schaetzl
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Ruben
authors.initials: R
authors.lastname: Ibanez
authors.forename: Christian
authors.initials: C
authors.lastname: Herzog
mesh_terms: D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006506:Hepatitis A / Q000517:prevention & control; D035922:Hepatitis A Antibodies / Q000097:blood; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D017957:Hepatitis A Virus, Human / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007557:Israel; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage*; D023321:Poliovirus Vaccines / Q000008:administration & dosage*; D022721:Vaccines, Virosome / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D022542:Measles-Mumps-Rubella Vaccine; D023321:Poliovirus Vaccines; D022721:Vaccines, Virosome