A combination MMR-varicella vaccine can be substituted for the second dose of the MMR vaccine or for the second doses of coadministered MMR and varicella vaccines in children aged 4–6 years, reported Dr. Keith S. Reisinger of Primary Physicians Research in Pittsburgh, and his associates.
Dr. Reisinger and his colleagues found postvaccination seropositivity rates of nearly 100% for the combination measles, mumps, rubella, and varicella vaccine (ProQuad) in a randomized, double-blind multicenter study sponsored by Merck & Co., including 799 healthy children (Pediatrics 2006;117:265–72).
Dr. Reisinger serves as a speaker for Merck and receives research money from the company.
The children had received their primary doses of the measles, mumps, and rubella vaccine (Merck-brand MMRII vaccine) and the varicella vaccine (Varivax) at age 12 months or older at least 1 month before their enrollment in the study.
A total of 399 children received ProQuad as a single injection, plus a placebo, while 205 children received the standard MMRII plus a placebo, and 195 received MMRII plus Varivax. About half the children (53%) were male, most (79%) were white, and their mean age was 4 years.
Overall, the immune responses to all four viruses, as measured by geometric mean titers (GMTs), in children who received ProQuad were statistically similar to those in children who received the other vaccines, although there were differences in GMTs with respect to the individual viruses. The GMTs of antibodies to mumps alone were statistically lower in the ProQuad group, compared with the other groups, but the GMTs of antibodies to rubella and varicella in the ProQuad group were higher, compared with the other groups, Dr. Reisinger and his associates wrote.
No severe vaccine-related adverse events were reported, and the percentages of any adverse events were similar among the groups. The most common problems were fever, nasopharyngitis, and cough. There were no significant differences in injection-site adverse experiences in the ProQuad group, compared with the other groups.
The concentration of varicella vaccine virus was higher in the ProQuad vaccine than in the current Varivax varicella vaccine, but the concentrations of measles, mumps, and rubella viruses were the same as those in the current MMRII vaccine.
Dr. Reisinger said in an interview that the development of a combined vaccine to provide protection against four diseases—measles, mumps, rubella, and varicella (MMRV)—is an important step in children's health for a number of reasons. Although the utilization rates for MMR are approximately 93%, the rates for varicella vaccination have been significantly lower.
“The use of MMRV will increase varicella protection in a similar fashion that MMR did for lagging mumps and rubella vaccine utilization in the early ′70s. Secondly, some parents and physicians are concerned about the high number of injections that infants receive in the first 2 years of life. The use of MMRV will be helpful in reducing the number of shots,” he said.
“Although the above factors are important, the largest issue to me is the need [for the United States] to move toward a two-dose varicella policy. Every vaccine has a primary failure rate. For MMR this primary failure rate is corrected through the recommendation of two doses.
“The combination of lower utilization rates of varicella with the primary vaccine failure rate may allow many children to reach adulthood with susceptibility to varicella. Adults have a much higher rate of morbidity and mortality from a varicella infection.
“If the United States adopts a second varicella dose recommendation (as surely it must), then the combined MMRV administered at 4–6 years of age will be the vaccine of choice to accomplish this,” he said.