title: Immunogenicity and safety of two tetravalent (measles, mumps, rubella, varicella) vaccines coadministered with hepatitis a and pneumococcal conjugate vaccines to children twelve to fourteen months of age.
abstract: BACKGROUND
  This study compared single-dose tetravalent measles, mumps, rubella, varicella vaccine, Priorix-Tetra, stored refrigerated (GSK+4C) or frozen (GSK-20C), with ProQuad (Merck-20C), when coadministered with hepatitis A vaccine (HAV) and 7-valent pneumococcal conjugate vaccine (PCV7).
  
  
  METHODS
  Multicenter, observer-blind phase 2 study in 1783 healthy 12-14 month olds randomized to: GSK+4C (n = 705), GSK-20C (n = 689) or Merck-20C (n = 389), administered concomitantly with HAV (Havrix) and PCV7 (Prevnar). Seroresponse rates and antibody geometric mean concentrations/titers were determined from enzyme-linked immunosorbent assay and neutralization assays. Reactogenicity and safety were assessed.
  
  
  RESULTS
  Seroresponse rates (day 42) were >97% for measles and rubella viruses and >92% for mumps virus, in all groups. Noninferiority of both GSK+4C and GSK-20C vaccines versus Merck-20C was demonstrated for seroresponse rates to measles, mumps and rubella viruses (lower 97.5% confidence interval above -5%, -10% and -5%, respectively). For varicella-zoster virus, seroresponse rates were 57.1%, 69.8% and 86.7% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. Noninferiority was not shown for either GSK vaccine (lower 97.5% confidence intervals <-15%). Geometric mean concentration ratios for anti-varicella-zoster virus demonstrated noninferiority (lower 97.5% confidence interval ≥ 0.5) versus Merck-20C for GSK-20C only. Geometric mean concentration ratios for antibodies to HAV and to PCV7 pneumococcal serotypes also met criteria for noninferiority for both GSK groups compared with Merck-20C. GSK vaccine safety was observed comparable to Merck-20C. Localized but not generalized measles/rubella-like rash and grade 3 fever was reported slightly more frequently with GSK vaccines, but antipyretic use was similar. The incidence of subjects experiencing at least 1 serious adverse event was 2.0%, 2.9% and 1.8% in the GSK+4C, GSK-20C and Merck-20C groups, respectively.
  
  
  CONCLUSIONS
  Noninferiority of both GSK measles, mumps, rubella, varicella vaccines versus Merck-20C was demonstrated for responses to measles, mumps and rubella viruses but was not fully demonstrated for varicella-zoster virus. The vaccines showed acceptable reactogenicity/safety when coadministered with HAV and PCV7.
authors.affiliation: Pediatric Alliance, Pittsburgh, PA, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Blatter
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Julie S
authors.initials: JS
authors.lastname: Shepard
authors.forename: Michael
authors.initials: M
authors.lastname: Leonardi
authors.forename: Steven
authors.initials: S
authors.lastname: Shapiro
authors.forename: Martin
authors.initials: M
authors.lastname: Schear
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Mufson
authors.forename: Judith M
authors.initials: JM
authors.lastname: Martin
authors.forename: Meera
authors.initials: M
authors.lastname: Varman
authors.forename: Stanley
authors.initials: S
authors.lastname: Grogg
authors.forename: Arnold
authors.initials: A
authors.lastname: London
authors.forename: Pierre
authors.initials: P
authors.lastname: Cambron
authors.forename: Martine
authors.initials: M
authors.lastname: Douha
authors.forename: Ouzama
authors.initials: O
authors.lastname: Nicholson
authors.forename: Christopher
authors.initials: C
authors.lastname: da Costa
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D019433:Chickenpox Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D005260:Female; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D053061:Herpes Zoster Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D022362:Hepatitis A Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D053061:Herpes Zoster Vaccine; D022542:Measles-Mumps-Rubella Vaccine; D022242:Pneumococcal Vaccines; C577557:Priorix-Tetra vaccine