Immunogenicity and safety of a second dose of measles-mumps-rubella-varicella vaccine in healthy children aged 5 to 6 years

Background: Two doses of measles-mumps-rubella (MMR) vaccine are recommended for elimination of these diseases in countries with universal mass vaccination; a 2-dose program is also likely to be required for elimination of childhood varicella and has recently been provisionally recommended in the United States. Given the overlap in MMR and varicella vaccination schedules, development of a combined vaccine appears logical and would facilitate the introduction of 2 doses of varicella vaccination in healthy children with no additional injections. Methods: The immunogenicity and safety of a second dose of an experimental MMR-varicella (MMRV) vaccine was assessed in an open-label phase III study (208136/017) in healthy children aged 5 to 6 years who had previously received a first dose of either MMRV (N = 48) or a licensed MMR vaccine (N = 45) in the second year of life. Results: After administration of MMRV at 5 to 6 years of age, all subjects were seropositive for measles, rubella and varicella antibodies and only one subject in the MMRV group remained seronegative for mumps antibodies. Ratios of postover prevaccination geometric mean titers for antibodies against measles, mumps and rubella did not differ between the 2 study groups. A 5.2-fold increase (95% confidence interval: 3.5-7.8) in antivaricella antibody geometric mean titers was seen in initially seropositive subjects in the MMRV group after administration of the second vaccine dose. Local symptoms after the second dose of MMRV were more common in the MMRV group than in the MMR group. The incidence of fever was low in both groups compared with that usually seen after a first dose of MMR or MMRV vaccine. Conclusion: This experimental tetravalent MMRV vaccine appears well suited for use in national immunization programs in place of a second dose of MMR or MMR plus varicella in children who have already received a first dose of MMR.