Safety and immunogenicity of a combination measles, mumps, rubella and varicella vaccine (ProQuad).

BACKGROUND: A combination measles, mumps, rubella, and varicella vaccine (ProQuad, Merck & Co., Inc, West Point, PA) was evaluated in five clinical trials. Use of ProQuad would result in fewer injections for children and would facilitate universal immunization against all four diseases. OBJECTIVE: To describe the combined results obtained from the studies conducted during the clinical development program for ProQuad. METHODS: A total of 5833 healthy children, 12-23 months of age, and 399 healthy children, 4-6 years of age, received 1 or 2 doses of ProQuad in five controlled clinical trials. M-M-R II and VARIVAX were used as the control for most studies. Safety was evaluated for six weeks postvaccination and immunogenicity was assessed six weeks after each dose by a sensitive assay (ELISA or gpELISA). RESULTS: A single dose of ProQuad in 12- to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R II and VARIVAX and was generally well tolerated. ProQuad can be used concomitantly with other vaccines (hepatitis B and Hoemophilus influenzoe b). A higher rate of fever was reported after 1 dose of ProQuad compared to M-M-R II and VARIVAX, but fever episodes were transient without long-term sequelae. Both a 2-dose regimen of ProQuad in 12- to 23-month-olds and use of ProQuad in place of M-M-R II at 4-6 years were shown to be immunogenic and well tolerated. The incidence of adverse experiences following a second dose of ProQuad was lower than that following the initial dose. CONCLUSIONS: A single dose of ProQuad is as immunogenic as M-M-R II and VARIVAX and is well tolerated in a 1- or 2-dose schedule. ProQuad should easily fit into the routine immunization schedule.

A combination measles, mumps, rubella, and varicella vaccine (ProQuad) given to 4- to 6-year-old healthy children vaccinated previously with M-M-RII and Varivax.

BACKGROUND: In the United States, children receive primary doses of M-M-RII (Merck & Co, Inc, West Point, PA) and Varivax (Merck & Co, Inc) beginning at 12 months, often at the same health care visit. Currently a second dose of M-M-RII is given to 4- to 6-year-old children, to increase vaccination rates and to reduce the number of individuals without detectable antibodies. A second dose of a varicella-containing vaccine may result in similar benefits. OBJECTIVES: To demonstrate that ProQuad (measles, mumps, rubella, and varicella virus vaccine live; Merck & Co, Inc) may be given in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children. METHODS: Four- to 6-year-old children who had been immunized previously with M-M-RII and Varivax were assigned randomly to receive either ProQuad and placebo (N = 399), M-M-RII and placebo (N = 195), or M-M-RII and Varivax (N = 205) and were then monitored for safety and immunogenicity. RESULTS: ProQuad was generally well tolerated. Similarity (noninferiority) was demonstrated in postvaccination antibody responses to measles, mumps, and rubella between recipients of ProQuad and all recipients of M-M-RII and in responses to varicella between recipients of ProQuad and recipients of Varivax. Postvaccination seropositivity rates for antibodies against all 4 viruses were nearly 100% in all 3 groups. Small fold increases were observed for measles, mumps, and rubella antibody titers. In contrast, substantial boosts in varicella antibody titers were observed among recipients of a second dose of varicella vaccine, administered as ProQuad or Varivax. CONCLUSIONS: ProQuad may be used in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children.

Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children.

BACKGROUND: A quadrivalent measles, mumps, rubella and varicella vaccine would facilitate universal immunization against all 4 diseases, improve compliance and immunization rates and decrease the number of injections given to children and visits to physicians' offices. OBJECTIVES: To evaluate 1- and 2-dose regimens of a combined measles, mumps, rubella and varicella vaccine (ProQuad, referred to as MMRV) manufactured with a varicella component of increased potency. METHODS: In this partially blind, multicenter study, 480 healthy 12- to 23-month-old children were randomized to receive either MMRV and placebo or M-M-RII and VARIVAX. Injections were given concomitantly at separate sites. Subjects randomized to receive MMRV and placebo received a second dose of MMRV 90 days later. Subjects were followed for 42 days after each vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after each vaccination. RESULTS: Measles-like rash and fever during days 5-12 were more common after the first dose of MMRV (rash, 5.9%; fever, 27.7%) than after M-M-RII and VARIVAX (rash, 1.9%; fever, 18.7%). The incidence of other adverse events were similar between groups. Response rates were >90% to all vaccine components in both groups. Geometric mean titers to measles and mumps were significantly higher after 1 dose of MMRV than after administration of M-M-RII and VARIVAX. The second dose of MMRV elicited slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer (from 13.0 to 588.1 glycoprotein antigen-based enzyme-linked immunosorbent assay units/mL). CONCLUSION: A 1- or 2-dose regimen of MMRV is generally well-tolerated when administered to 12- to 23-month-old children and has a safety and immunogenicity profile similar to that of M-M-RII and VARIVAX administered concomitantly.