Immunogenicity and Safety of Two Tetravalent (Measles, Mumps, Rubella, Varicella) Vaccines Co-Administered with Hepatitis A and Pneumococcal Conjugate Vaccines to Children 12 14 Months of Age

BACKGROUND:: This study compared single-dose tetravalent measles, mumps, rubella, varicella (MMRV) vaccine, Priorix-Tetra, stored refrigerated (GSK+4C) or frozen (GSK 20C), with ProQuad (Merck-20C), when co-administered 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 (GMC/GMT) were determined from ELISA 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. Non-inferiority 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% CIs above -5%, -10%, and -5%, respectively). For varicella-zoster virus (VZV), seroresponse rates were 57.1%, 69.8%, and 86.7% in the GSK+4C, GSK-20C, and Merck-20C groups, respectively. Non-inferiority was not shown for either GSK vaccine (lower 97.5% CIs <-15%). GMC ratios for anti-VZV demonstrated non-inferiority (lower 97.5% CI >/=0.5) versus Merck-20C for GSK-20C only. GMC ratios for antibodies to HAV and to PCV7 pneumococcal serotypes also met criteria for non-inferiority 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 one serious adverse event was 2.0%, 2.9% and 1.8% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. CONCLUSIONS:: Non-inferiority of both GSK MMRV vaccines versus Merck-20C was demonstrated for responses to measles, mumps and rubella viruses, but was not fully demonstrated for VZV. The vaccines showed acceptable reactogenicity/safety when co-administered with HAV and PCV7.

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