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

Pediatr Infect Dis J. 2012 Aug;31(8):e133-40. doi: 10.1097/INF.0b013e318259fc8a.

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.

Trial registration: ClinicalTrials.gov NCT00578175.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • Chickenpox Vaccine / administration & dosage*
  • Chickenpox Vaccine / adverse effects
  • Chickenpox Vaccine / immunology
  • Female
  • Hepatitis A Vaccines / administration & dosage*
  • Hepatitis A Vaccines / adverse effects
  • Hepatitis A Vaccines / immunology
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Herpes Zoster Vaccine / administration & dosage*
  • Herpes Zoster Vaccine / adverse effects
  • Herpes Zoster Vaccine / immunology
  • Humans
  • Infant
  • Male
  • Measles-Mumps-Rubella Vaccine / administration & dosage*
  • Measles-Mumps-Rubella Vaccine / adverse effects
  • Measles-Mumps-Rubella Vaccine / immunology
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Chickenpox Vaccine
  • Hepatitis A Vaccines
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Herpes Zoster Vaccine
  • Measles-Mumps-Rubella Vaccine
  • Pneumococcal Vaccines
  • Priorix-Tetra vaccine

Associated data

  • ClinicalTrials.gov/NCT00578175