Mumps, Rubella And Varicella Vaccine Research Articles

The Implementation and Impact of a Revised National Childhood Immunization Schedule in an Urban Asian Community.

Changes to the national childhood immunization schedule (NCIS) can have a potential impact on vaccine uptake in the community. The NCIS in Singapore has undergone several revisions over the years, with the most recent modification on 1 November 2020. The new NCIS includes, as routine, the influenza and the varicella vaccine, as well as two combination vaccines, the measles, mumps, rubella and varicella vaccine (MMRV), and the hexavalent diphtheria, acellular pertussis, tetanus, haemophilus influenza b, injectable polio, and hepatitis B vaccine (6-in-1). This retrospective database study aims to assess the effect of the new NCIS on (a) the vaccination uptake of children at 6 and 12 months and (b) the cost difference to the healthcare system and to parents. One-year vaccination data from two cohorts of children immunized according to the old (n = 10,916) and new NCIS (n = 10,299) were extracted, respectively, from their electronic medical records. The vaccine uptake at 6 and 12 months increased by 10.8 and 2.1%, respectively, with the new NCIS as compared to the old NCIS. The mean number of required visits to the primary care clinic for each child was reduced from six to four. There is an estimated 6.41% cost reduction with the new NCIS.

Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

Assessment of the Clinical and Economic Impact of Different Immunization Protocols of Measles, Mumps, Rubella and Varicella in Internationally Adopted Children.

The appropriate immunization of internationally adopted children (IAC) is currently under debate and different approaches have been suggested. The aim of this study is to evaluate the clinical and economic impact of different strategies of measles, mumps, rubella, and varicella (MMRV) immunization in IAC in Italy. A decision analysis model was developed to compare three strategies: presumptive immunization, pre-vaccination serotesting and vaccination based on documentation of previous immunization. Main outcomes were the cost of strategy, number of protected IAC, and cost per child protected against MMRV. Moreover, the incremental cost-effectiveness ratio (ICER) was calculated. The strategy currently recommended in Italy (immunize based on documentation) is less expensive. On the other hand, the pre-vaccination serotesting strategy against MMRV together, improves outcomes with a minimum cost increase, compared with the presumptive immunization strategy and compared with the comparator strategy. From a cost-effectiveness point of view, vaccination based on serotesting results in being the most advantageous strategy compared to presumptive vaccination. By applying a chemiluminescent immunoassay test, the serology strategy resulted to be clinically and economically advantageous. Similar results were obtained excluding children aged <1 year for both serology methods. In conclusion, based on our analyses, considering MMRV vaccine, serotesting strategy appears to be the preferred option in IAC.

Immunogenicity and safety of intramuscular versus subcutaneous administration of a combined measles, mumps, rubella, and varicella vaccine to children 12 to 18 months of age

ABSTRACT This randomized trial conducted in France compared intramuscular (IM) and subcutaneous (SC) administration of two doses of a measles, mumps, rubella, and varicella (MMRV) combination vaccine (ProQuad®) administered one month apart to 405 children 12–18 months of age (NCT00402831). The 2-dose regimen of MMRV administered IM was shown to be as immunogenic as the 2-dose regimen administered SC for all antigens 6 weeks post-vaccination for the subjects who were initially seronegative for measles, mumps, rubella, or varicella (lower bounds of the two-sided 95% CIs for the difference in response rates for all antigens greater than −10% [range −2.1 for varicella to −3.0 for mumps]). The antibody response rates for all vaccine antigens 6 weeks after the second dose of MMRV were > 99% in both the IM and SC groups. Fewer subjects in the IM group experienced injection-site AEs compared with the SC group (17.8% and 28.6% post-dose 1, and 20.4% and 29.5% post-dose 2, respectively). From Day 0 to Day 4 post-dose 2, fewer subjects reported erythema and swelling in the IM group than in the SC group (15.4% and 27.0%, and 6.0% and 12.5%, respectively). In both groups, most injection-site AEs started during the first four days after vaccination; their intensity was mainly mild or ≤2.5 cm. The rates of fever were comparable between the two groups after each dose of MMRV. In conclusion, two doses of the MMRV vaccine were highly immunogenic and well tolerated when administered either SC or IM. ClinicalTrials.gov Identifier: NCT00402831

Avaliação da legislação e normas vigentes para bioensaios aplicados em pesquisa clínica: um estudo de caso para comprovação de imunogenicidade de vacinas

Vaccines are immunobiologicals products considered safe, effective and essential to control and / or eradication of vaccine-preventable diseases, and they were submitted to analytical tests and bioassays to check the quality and therapeutic efficacy. In this study was evaluated the applicability of the Executive Director Resolution of the National Health Surveillance Agency, (Anvisa), RDC no 27 May 17, 2012 and analyzed the other standardized bioassays documents recommended to the World Health Organization, Food and Drug Administration, United States Pharmacopeia, European Medicines Agency and data literature. The analyses of data literature and regulation statutes showed inconsistent guidelines. This study showed that is essential create a more targeted legislation to respond the particularities of bioanalytical assays in clinical trials to ascertain the vaccines immunogenicity. In order to corroborate with this guideline elaboration was carried out a case study by a standardized measles virus plaque reduction neutralization test in a 96-well plates (Micro-PRNT) to measure vaccinia neutralization according to RDC no 27 May 17, 2012, 27 focus on the effectiveness of tests that is used in vaccine generated immune responses studies. The results showed that the method provides the selectivity and specificity required for applicability in combination vaccines as MMR (mumps, measles and rubella) or MMRV (measles, mumps, rubella and varicella vaccine).

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process

ABSTRACTVaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRVAMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRVAMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRVAMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRVAMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRVAMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

Immunogenicity and reactogenicity of tetravalent vaccine for measles, mumps, rubella and varicella (MMRV) in healthy children: a meta-analysis of randomized controlled trials

Background: Varicella is a highly infectious childhood disease. Tetravalent measles–mumps–rubella–varicella (MMRV) vaccine was introduced as one-syringe dose. Objective: To evaluate the immunogenicity and reactogenicity of MMRV vaccine versus trivalent MMR with varicella (V) vaccines in healthy children and to assess the respective safety issue. Methods: Randomized controlled trials (RCTs) were searched from the OVID databases. Trials were eligible if healthy children were randomized to receive MMRV or MMR+V vaccine. Seroconversions in serum antibody titers were the primary outcomes; adverse events were the secondary outcomes. Results: Ten RCTs with 8961 healthy children were identified. MMRV and MMR+V vaccines showed comparable immunogenicity against measles (relative risk [RR] = 0.99, 95% CI = 0.98–1.00), mumps (RR = 0.99, 95% CI = 0.97–1.00), rubella (RR = 1.00, 95% CI = 1.00–1.01) and varicella (RR = 0.98, 95% CI = 0.95–1.01). At least 93% of children in both groups had seroconverted within 6 weeks. MMRV group showed significantly higher incidences of fever (RR = 1.19, 95% CI = 1.09–1.31) and rash (RR = 1.23, 95% CI = 1.06–1.43). Conclusions: The immunogenicities of MMRV and MMR+V vaccines were comparable in healthy children; however, MMRV vaccination showed higher incidences of fever and rash.

Analysis of safety data in children after receiving two doses of ProQuad® (MMRV)

BackgroundIn randomized clinical studies, over 11,800 children, 12 months to 6 years of age, were administered ProQuad®, a combination measles, mumps, rubella, and varicella vaccine (MMRV). This paper describes the safety following a 2-dose regimen of MMRV administered to children in the second year of life. MethodsSafety data from five clinical studies were combined for all children who were scheduled to receive two doses of MMRV ∼3–6 months apart. All vaccinated children were followed for safety following each dose of MMRV. ResultsOf 3112 children who received a first dose of MMRV, 2780 (89.3%) received a second dose of MMRV. Overall, 70.5% and 57.7% of children reported ≥1 adverse experiences following first and second doses of MMRV, respectively. Injection-site redness was statistically significantly higher postdose 2 than postdose 1, while injection-site pain/tenderness was statistically significantly higher postdose 1 compared to postdose 2. Rashes were statistically significantly lower postdose 2 compared to postdose 1. Ten febrile seizures (8 postdose 1, 2 postdose 2) were reported following MMRV vaccination. The incidence of febrile seizures postdose 1 of MMRV was 0.26% (8/3019) compared to 0.07% (2/2695) postdose 2 of MMRV. ConclusionsAdministration of two doses of MMRV has an acceptable safety profile in children 12 to 23 months of age. There is a small increase in the risk of febrile seizures following the first dose of MMRV as compared to the component vaccines, but the risk for any individual child is relatively low.

Safety of a 2-dose Regimen of a Combined Measles, Mumps, Rubella and Varicella Live Vaccine Manufactured With Recombinant Human Albumin

ProQuad, a vaccine containing antigens from M-M-RVAXPRO (measles, mumps and rubella vaccine) and VARIVAX (varicella vaccine), is indicated for simultaneous vaccination against measles, mumps, rubella and varicella (MMRV) in individuals from 12 months of age. To eliminate blood-derived products of human origin from the manufacturing process of the MMRV vaccine, recombinant human albumin was selected as a replacement for human serum albumin. This open-label, multicenter clinical trial (clinicaltrials.gov identifier NCT00560755) was designed to describe the safety profile of a 2-dose schedule of the MMRV vaccine at a 1-month interval in healthy children aged 12-22 months. In total, 3388 children received at least 1 dose of the MMRV vaccine. Overall, 3376 (99.65%) children were included in the post-dose 1 safety analysis and 3342 (98.64%) in the post-dose 2 safety analysis. After doses 1 and 2, the frequencies of children experiencing solicited injection-site reactions (post-dose 1: erythema 14.31%; swelling 5.57% and pain 10.31%; post-dose 2: erythema 30.46%; swelling 13.23% and pain 11.49%), rashes of interest (post-dose 1: 11.4%; post-dose 2: 2.78%), vaccine-related nonserious systemic adverse events (post-dose 1: 34.86%; post-dose 2: 13.4%) and temperature ≥39.4 °C (post-dose 1: 25.24%; post-dose 2: 12.06%) were consistent with those observed in previous studies of the MMRV vaccine manufactured with human serum albumin. Neither serious allergic-type adverse events nor anaphylactic reactions were reported. The results confirm the good safety profiles of MMRV and of measles, mumps and rubella vaccines manufactured with recombinant human albumin.

Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad®) in infants from 9 months of age

Vaccination against measles, mumps, rubella and varicella (MMRV) is currently recommended in developed countries for infants from 12 months of age. However, measles vaccination at 9 months of age is recommended by the WHO in the Expanded Program on Immunization (EPI) schedule and it is therefore possible that MMR or MMRV vaccines might also be given at this age.This open-label, randomised, comparative study evaluated the immunogenicity and safety of a 2-dose schedule of ProQuad® (MMRV vaccine) given at a 3-month interval in healthy infants aged ≥9 months. For measles, the non-inferiority of the response rate post-Dose 2 was reached when Dose 1 was administered at 11 months (98%) compared with 12 months (99%) but was not reached when Dose 1 was administered at 9 months (95%). The response rate to measles post-Dose 1 increased with age, from 73% to 88% and 90% at 9, 11 and 12 months, respectively. For mumps, rubella and varicella, response rates were not different after Dose 1 (>95%) or Dose 2 (>99%) regardless of whether Dose 1 was administered at 9, 11 or 12 months of age. In conclusion, the age of administration of the first of a two-dose regimen of ProQuad may be lowered to 11 months. Dose 1 may be administered at 9 months if early protection is required, but it should be recognised that a second dose is required promptly with a minimum of 3-month interval between doses.

Antibody persistence for 3 years following two doses of tetravalent measles–mumps–rubella–varicella vaccine in healthy children

Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).

Update: Recommendations From the Advisory Committee on Immunization Practices (ACIP) Regarding Administration of Combination MMRV Vaccine

On February 27, 2008, new information was presented to the Advisory Committee on Immunization Practices (ACIP) regarding the risk for febrile seizures among children aged 12-23 months after administration of the combination measles, mumps, rubella, and varicella (MMRV) vaccine (ProQuad, Merck & Co., Inc., Whitehouse Station, New Jersey). This report summarizes current knowledge regarding the risk for febrile seizures after MMRV vaccination and presents updated ACIP recommendations that were issued after presentation of the new information. These updated recommendations remove ACIP's previous preference for administering combination MMRV vaccine over separate injections of equivalent component vaccines (i.e., measles, mumps, and rubella [MMR] vaccine and varicella vaccine).

A combination vaccine against measles, mumps, rubella and varicella

A new combination vaccine against measles, mumps, rubella and varicella (MMRV) from GlaxoSmithKline Biologicals has recently been approved in Europe. It combines the components from two well-established, live, attenuated vaccines against measles, mumps and rubella. This review presents a summary of the development of this MMRV vaccine from published clinical studies. Seroconversion rates and antibody titers after the first and second dose are similar to those observed after concomitant administration of the MMR and varicella vaccines. Furthermore, the clinical profile of this combination vaccine, in terms of injection- site and general tolerability, is similar to that of the component vaccines. A higher incidence of low-grade fever has been noted following the first dose of MMRV vaccine, although it is no different from component vaccines following the second dose. MMRV vaccines were recommended in Germany in 2006 for administration in two doses to children aged 11-14 months and 15-23 months. They offer a convenient way to implement varicella vaccination and to achieve high vaccine coverage rates mirroring those of MMR vaccines. For other countries considering introducing these vaccines, the advantages for children, parents and healthcare providers of protecting against four diseases in a single vaccine should be noted.

The Safety and Immunogenicity of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

This clinical trial was conducted to demonstrate that each of 3 consistency lots of a combined measles, mumps, rubella and varicella vaccine (MMRV) would be well tolerated, induce clinically acceptable and similar immune responses to each antigen and induce immune responses similar to measles, mumps and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V). An additional objective was to evaluate the persistence of antibodies 1 year postvaccination. Study participants 12 to 23 months of age received a single injection of either one of 3 consistency lots of MMRV or MMR + V administered at separate injection sites. A total of 3,928 healthy children were enrolled at study sites in the United States and Canada. Immune responses to measles, mumps, rubella and varicella in children immunized with each of 3 lots of MMRV were similar and the combined response to all 3 lots was comparable to that of the control group. The 1-year antibody persistence rates for measles, mumps, rubella and varicella viruses were each greater than 95% and comparable among the recipients of the 3 consistency lots of MMRV and the control group. All vaccines were generally well tolerated during the 42 days after vaccination and the overall incidence of adverse experiences was comparable between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9 degrees C oral equivalent or tactile) were greater in recipients of MMRV than in recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and there was no difference in the incidence of febrile seizures. MMRV was generally well tolerated and had comparable immunogenicity and overall safety profiles to MMR + V administered concomitantly. Long-term persistence of antibodies after receipt of MMRV is expected based on similar antibody titers against all 4 antigens 1 year postvaccination compared with recipients of MMR and V.

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

A study was conducted to assess administration of a combination measles, mumps, rubella and varicella vaccine (MMRV) with other childhood vaccines. 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. 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. 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.

Dose-Response Study of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

A combined measles, mumps, rubella and varicella (MMRV) vaccine would facilitate universal immunization against 4 diseases by decreasing the number of injections and thus enhancing compliance and coverage rates. If a second dose of varicella vaccine were to be recommended, MMRV could be used to administer a routine second dose of M-M-RII with the added advantage of boosting varicella-zoster virus (VZV) antibody titers. Subjects 12-23 months of age received a single injection of 1 of 3 lots of an MMRV vaccine (ProQuad) containing high, middle or low VZV potency, or VARIVAX given concomitantly with M-M-RII. Recipients of MMRV received a second injection of MMRV approximately 90 days later. We enrolled 1559 subjects in the study. Antibody response rates to VZV 6 weeks after 1 injection of high potency MMRV (88.6%) or 2 injections of MMRV of any varicella potency (99.7-100%) were similar to the response rates after concomitant administration of M-M-RII and VARIVAX (93.1%). The second injection of MMRV boosted VZV antibody titers. Antibody responses to measles, mumps and rubella were >or=98%, similar to the control, after 1 or 2 injections of MMRV. MMRV was generally well-tolerated during the 42 days after vaccination. One injection of high potency MMRV resulted in antibody responses to the 4 vaccine components equivalent to those found after concomitant administration of M-M-RII and VARIVAX. A second injection of MMRV resulted in a significant boost in VZV antibody. This boost may translate into enhanced immunogenicity against varicella, which is known to correlate with increased protection.