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.

Safety and immunogenicity of a measles, mumps, rubella and varicella vaccine given with combined Haemophilus influenzae type b conjugate/hepatitis B vaccines and combined diphtheria-tetanus-acellular pertussis vaccines.

BACKGROUND: A study was conducted to assess administration of a combination measles, mumps, rubella and varicella vaccine (MMRV) with other childhood vaccines. METHODS: In this open, multicenter trial, 1915 healthy children ages 12-15 months were randomized into 3 groups: group 1, MMRV, combined Haemophilus influenzae type b conjugate-hepatitis B vaccines (Hib/HepB) and combined diphtheria-tetanus-acellular pertussis vaccines (DTaP) concomitantly; group 2, MMRV followed by Hib/HepB and DTaP 42 days later; group 3, MMR and varicella vaccine followed by Hib/HepB and DTaP 42 days later. RESULTS: Antibody responses to measles, mumps, rubella, varicella, Hib, HepB, diphtheria and tetanus were similar between groups 1 and 2 (all >95%, except varicella, 89.7% in group 1 and 90.9% in group 2). Pertussis toxin and filamentous hemagglutinin responses were significantly lower in group 1 than in group 2 (group 1, 74.1 and 67.1%; group 2, 90.4 and 86.8%, respectively). An exploratory analysis suggested that the difference in and pertussis toxin and filamentous hemagglutinin responses was likely the result of study design rather than interference among vaccine components because the groups differed in age of receipt of DTaP (group 1, approximately 12 months; group 2, approximately 13.5 months). When the groups were matched for age, sample size was sufficient for comparison only in children > or =13.5 months old. Pertussis toxin and filamentous hemagglutinin responses were similar in these children. The safety profiles for each vaccination regimen were comparable. CONCLUSIONS: The immunogenicity data support concomitant administration of MMRV with Hib/HepB. Limited data from an exploratory analysis indicate that MMRV can be administered concomitantly with DTaP. Concomitant administration of MMRV, Hib/HepB and DTaP is well-tolerated.

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.