The Food and Drug Administration's recent approval of the first combination vaccine designed to protect children against measles, mumps, rubella, and varicella is raising expectations of improved immunization rates, but is also eliciting some concerns.
The quadrivalent MMRV vaccine Proquad, developed by Merck and Co., Inc., is a combination of the company's measles, mumps, and rubella (MMR II) and varicella (Varivax) vaccines.
“Right now, at the 1-year visit, we're giving kids four or five shots. That's a lot. Anything that gets the number down while providing the same protection is a good thing. It's not revolutionary, but it's beneficial,” said Robert W. Frenck Jr., M.D., a member of the American Academy of Pediatrics' Committee on Infectious Diseases and a professor of pediatrics at the University of California, Los Angeles.
The need for one less shot, and potentially one fewer office visit, might close the gap between vaccination rates for varicella and for measles, mumps, and rubella. “It's likely that use of the combination vaccine will help get the varicella vaccination numbers up,” said Jay Lieberman, M.D., of the UCLA Center for Vaccine Research in Torrance, California.
In 2004, the immunization rate for varicella was estimated to be 87.5%, compared with 93% for measles, mumps, and rubella, according to a press release issued by Merck.
Dr. Lieberman coauthored one of a handful of studies comparing the immunogenicity of the MMVR injection with the standard two-shot MMR II and varicella immunizations.
The Merck-funded study showed that seroconversion rates were similar in children receiving the one- and two-shot regimens, as well as among children who received different lots of the MMRV vaccine. The latter measure, which was necessary for FDA approval, demonstrated the ability to manufacture the vaccine consistently, said Dr. Lieberman.
In this and similar studies, children injected with the MMRV vaccine suffered more fevers following the inoculations than those who received the independent MMR and varicella vaccines; however, “the fevers were mild and not clinically relevant,” according to Dr. Lieberman. There was no statistically significant difference in the incidence of more worrisome adverse febrile events, including febrile seizures, he said, noting that overall the one- and two-shot regimens appear to be similarly tolerated.
The FDA approved the quadrivalent vaccine for children between the ages of 12 months and 12 years, including those in need of a second dose of the MMR II vaccine.
Because the recommendation for MMR II has been to give two doses—the first at age 12–15 months and the second prior to school entry at age 4–6 years—adoption of the quadrivalent vaccine would make the ongoing debate over the need for a second dose of the varicella vaccine irrelevant, said Richard K. Zimmerman, M.D., of the department of family medicine at the University of Pittsburgh, Pennsylvania, and a voting member of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP).
“A second dose of varicella vaccine should reduce the number of breakthrough cases of chickenpox that we've seen, but the ACIP has not yet recommended a second dose,” Dr. Zimmerman said. In fact, in June of this year, the ACIP rejected a proposal recommending children be given booster shots of the varicella vaccine after age 4. “This was due in part to questions about cost and waiting for a combination vaccine such as MMRV to make it more feasible.”
If the ACIP recommends a second dose of varicella vaccine, “then MMRV should be easily accepted, although cost could be a barrier,” said Dr. Zimmerman.
According to Merck, the price for Proquad is $114.61 per shot, compared with $104 for the combination of the MMR II and Varivax vaccines, which cost $38 and $66, respectively.
Some immunization watchdog groups are urging caution. “Combining this many live viruses into one vaccine is something that has never been done before, and there is not enough information about possible long-term effects,” said Barbara Loe Fisher, president of the National Vaccine Information Center.
“There may be some concerns about delivering more antigens in a single shot, but there is no scientific evidence that this is a problem,” said Dr. Frenck. “These viruses are all attenuated, and four is nothing compared to the number of viruses and bacteria that we are all exposed to every day.”