Immunogenicity and Safety of the New MMRV Vaccine
Immunogenicity and Safety of the New MMRV Vaccine
Abstracts & Commentary
By Hal B. Jenson, MD, FACP, Chair, Department of Pediatrics, Director, Center for Pediatric Research, Eastern Virginia Medical School and Children’s Hospital of the King’s Daughters, Norfolk, VA, is Associate Editor for Infectious Disease Alert.
Dr. Jenson is on the speaker’s bureau for Merck.
Synopsis: In these 2 studies, the quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccine, with increased potency of varicella compared to the current monovalent varicella vaccine, provides a varicella response rate of 81% and 91% after 1 dose, and 99% and 100% after 2 doses. One dose of MMRV is immunologically comparable to separate administration of measles-mumps-rubella and varicella vaccines in healthy children 12-23 months of age.
Sources: Shinefield H, et al. Evaluation of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children. Pediatr Infect Dis J. 2005;24:665-669; Shinefield H, et al. Dose-Response Study of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children. Pediatr Infec Dis J. 2005;24:670-675.
The quadrivalent Measles, Mumps, Rubella, and Varicella (MMRV) vaccine was studied in 480 healthy children 12-23 months of age who were randomized 2:1 to receive either MMRV (4.81 log10 PFU of varicella) and placebo (323 children) or the current measles-mumps-rubella (MMR-II) and varicella (Varivax) vaccines (157 children). Injections were given concomitantly at separate sites. Children receiving MMRV and placebo received a second dose of MMRV 90 days later. Immunogenicity at 6 weeks showed that the response rates to all vaccine components were > 90% in both groups. Geometric mean titers (GMT) to measles (1.4 fold increase, 95% CI, 1.2-1.7 fold increase) and mumps (1.4 fold increase, 95% CI, 1.1-1.7 fold increase) were significantly higher after 1 dose of MMRV than after administration of MMR and varicella vaccines. The second dose of MMRV resulted in increased GMT for all components, with the greatest increase for varicella (588.1 gpELISA units/mL after 2 doses vs 13.0 gpELISA units/mL after 1 dose).
Vaccinations were well-tolerated. Measles-like rash and fever during the 5-12 days after MMRV (rash, 5.9%; fever, 27.7%) were significantly more frequent than after MMR and varicella vaccines (rash, 1.9%; fever, 18.7%).
The quadrivalent MMRV vaccine was also studied in 1559 healthy children from 11-23 months of age. Children were randomized 1:1:1:1 to receive MMRV with low potency varicella (3.48 log10 PFU), MMRV with middle potency varicella (3.97 log10 PFU), MMRV with high potency varicella (4.25 log10 PFU), or separate injections of MMR vaccine and varicella vaccine, as a control group. Children receiving MMRV were administered a second dose of MMRV at 90 days. The subgroups were comparable with respect to age (overall mean of 12.9 months), race (including 66% Caucasian and 15% African American), and gender (54% male and 46% female).
Response rates to varicella after 1 dose of the 3 combination vaccine lots were 64% (low potency), 81% (middle potency), and 87% (high potency), and geometric mean titers (GMT) were 5.7, 10.5, and 11.9, respectively, compared to a response rate of 93% and GMT of 16.5 for the control group. Hypothesis testing of similarity demonstrated that 2 injections of MMRV (low, middle, and high dose) and 1 injection of MMRV (high dose) were comparable to separate MMR and varicella vaccinations, in terms of response rate. (> 5 gpELISA units/mL, a value that has been shown to correlate with protection). The GMT responses after 2 injections of MMRV (low, middle, and high dose) and 1 injection of MMRV (middle and high doses) were similar to separate MMR and varicella vaccinations. Response rates for measles, mumps, and rubella were comparable (98.2% to 100%) after 1 dose for all groups, including the control group. The GMT for measles was higher for MMRV (middle and high doses) compared to the control group (1.2 fold increase, 95% CI, 1.1-1.4 for each).
Vaccinations were well-tolerated. The incidence of injection site reactions was comparable for the 3 combination vaccines after 1 or 2 doses (30% and 22% for low potency, 27% and 22% for middle potency, and 27% and 20% for low potency) compared to that of the control group (28% at the MMR site and 30% at the varicella site). During the first 42 days after the first vaccination, as reported by the parents, the incidence of fever (31%, 34%, and 39%) and duration of fever (1.6, 1.5, and 1.9 days) were comparable to the control group (36% and 1.6 days, respectively). There was a significantly lower incidence of fever after the second MMRV (23%, 27%, and 28%) compared to the control group. The incidence of rash was comparable to the incidence of rash from varicella vaccine alone. Only one adverse event, a febrile seizure 8 days after MMRV with middle potency, was assessed to be vaccine-related.
Commentary
Earlier studies demonstrated that combining varicella vaccine with MMR vaccine results in lower antibody response rates and GMTs for varicella and higher GMTs for measles, with no appreciable differences for mumps and rubella. These results suggest that, when combined in a single vaccine, the measles component interferes with the varicella component. It has been shown previously that acceptable varicella GMTs are achievable using MMRV containing a higher varicella potency (4.81 log10PFU) than that used in the monovalent varicella vaccine. These new studies show that a single vaccination with MMRV with ~4.25 log10PFU of varicella induces comparable immunity to separate injections with MMR-II and varicella vaccines. Furthermore, a second injection of all 3 MMRV formulations yielded response rates and GMTs comparable to the control group for all vaccine components. A second MMRV dose resulted in significant increases both of varicella response (≥ 5 gpELISA units/mL) seroconversion among the small number of subjects who had not responded to the first MMRV dose, and in varicella GMT.
The Food and Drug Administration (FDA) recently approved the combined MMRV produced by Merck & Co., Inc. and marketed as ProQuad®. This vaccine is licensed for children 12 months to 12 years of age. This formulation contains "a minimum of 3.99 log10 PFU," at product expiry comparable to the middle potency vaccine used in the current study. The results of combined studies reported in the product circular indicate that the overall response rates among 5446 children 12 to 23 months of age were 97.4% for measles, 95.8%-98.8% for mumps , 98.5% for rubella, and 91.2% for varicella. Response rates after a second dose were 98-99% for the 4 antigens with 2-fold increases in GMT for measles, mumps, and rubella and a 41-fold increase in GMT for varicella.
Both the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics are reviewing these data and are expected to announce soon guidelines for the recommended use of MMRV in the childhood immunization schedule. The results of this study, as well as the 10-year efficacy study of 1 vs 2 doses of the monovalent varicella vaccine, indicate that 2 doses of this MMRV vaccine may be the optimal immunogenic strategy for routine childhood immunization. This fits well with the current recommendation for 2 doses of MMR vaccine. It is likely that the first dose of MMRV vaccine will be recommended to be given at 12-15 months, the same as the current recommendation for the first dose of MMR vaccine, with a second dose at least 3 months later in selected circumstances. Because of the concern for interference, if MMR and varicella vaccine are not administered at the same time, at least 30 days should elapse between a dose of measles-containing vaccine and varicella vaccine.
Synopsis: In these 2 studies, the quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccine, with increased potency of varicella compared to the current monovalent varicella vaccine, provides a varicella response rate of 81% and 91% after 1 dose, and 99% and 100% after 2 doses.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.