Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine
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.
Current vaccination rates against measles, mumps and rubella have reached nearly universal coverage (~93%) in the United States. However, despite recommendations by the Advisory Committee on Immunization Practices, varicella vaccination has reached only ~84% of children in the United States, and coverage rates for all 4 diseases are substantially lower in other countries. A quadrivalent vaccine might improve compliance and immunization rates by decreasing the number of injections given to children.
The purpose of this study was to evaluate the safety, tolerability and immunogenicity of 1 or 2 doses of an investigational combined measles, mumps, rubella and varicella (Oka/Merck) vaccine live (ProQuad; Merck & Co., Inc., West Point, PA), hereafter referred to as MMRV, compared with the concomitant administration at separate injection sites of the commercially available measles, mumps and rubella vaccine live (M-M-RII; Merck & Co., Inc.) and varicella virus vaccine (Oka/Merck) live (VARIVAX; Merck & Co., Inc.), hereafter referred to as MMR and VV, respectively. An early formulation of the Merck quadrivalent vaccine (MMRV) was administered in previous studies to ~1500 healthy children 12 months-6 years of age and was generally well-tolerated and immunogenic with respect to measles, mumps and rubella. However, the seroconversion rates and geometric mean titers (GMTs) to varicella-zoster virus (VZV) afforded by this early MMRV were lower than those after the standard immunization with MMR and VV administered at the same time but at separate injection sites.
This study was designed to evaluate whether a higher dose of the VZV component in MMRV could overcome the decrease in varicella GMTs observed in previous studies. It represents the first evaluation of 1- and 2-dose regimens of MMRV manufactured with an upgraded process to increase the potency of the VZV component to 4.81 log10 plaque-forming units/0.5-mL dose. A previous study comparing 1 versus 2 doses of varicella vaccine showed that 2 doses given 3 months apart significantly increased GMTs and slightly reduced the frequency of breakthrough disease. Therefore the immunogenicity and safety of a second dose of MMRV were also tested.
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.
Current vaccination rates against measles, mumps and rubella have reached nearly universal coverage (~93%) in the United States. However, despite recommendations by the Advisory Committee on Immunization Practices, varicella vaccination has reached only ~84% of children in the United States, and coverage rates for all 4 diseases are substantially lower in other countries. A quadrivalent vaccine might improve compliance and immunization rates by decreasing the number of injections given to children.
The purpose of this study was to evaluate the safety, tolerability and immunogenicity of 1 or 2 doses of an investigational combined measles, mumps, rubella and varicella (Oka/Merck) vaccine live (ProQuad; Merck & Co., Inc., West Point, PA), hereafter referred to as MMRV, compared with the concomitant administration at separate injection sites of the commercially available measles, mumps and rubella vaccine live (M-M-RII; Merck & Co., Inc.) and varicella virus vaccine (Oka/Merck) live (VARIVAX; Merck & Co., Inc.), hereafter referred to as MMR and VV, respectively. An early formulation of the Merck quadrivalent vaccine (MMRV) was administered in previous studies to ~1500 healthy children 12 months-6 years of age and was generally well-tolerated and immunogenic with respect to measles, mumps and rubella. However, the seroconversion rates and geometric mean titers (GMTs) to varicella-zoster virus (VZV) afforded by this early MMRV were lower than those after the standard immunization with MMR and VV administered at the same time but at separate injection sites.
This study was designed to evaluate whether a higher dose of the VZV component in MMRV could overcome the decrease in varicella GMTs observed in previous studies. It represents the first evaluation of 1- and 2-dose regimens of MMRV manufactured with an upgraded process to increase the potency of the VZV component to 4.81 log10 plaque-forming units/0.5-mL dose. A previous study comparing 1 versus 2 doses of varicella vaccine showed that 2 doses given 3 months apart significantly increased GMTs and slightly reduced the frequency of breakthrough disease. Therefore the immunogenicity and safety of a second dose of MMRV were also tested.