Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine co-administered with a booster dose of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in healthy children aged 12–23 months Immunogenicity and safety of combined measles-mumps-rubella-varicella vaccine using new measles and rubella working seeds in healthy children in Taiwan and Singapore Reactogenicity and immunogenicity of a live attenuated tetravalent measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity and Safety of MMRV and PCV-7 Administered Concomitantly in Healthy Children 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 Incidence of febrile seizures in Finland: prospective population-based study. Safety of a 2-dose Regimen of a Combined Measles, Mumps, Rubella and Varicella Live Vaccine Manufactured With Recombinant Human Albumin Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial Safety and Immunogenicity of Early Vaccination with Two Doses of Tetravalent Measles-Mumps-Rubella-Varicella (MMRV) Vaccine in Healthy Children from 9 Months of Age Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine administered concomitantly with measles, mumps, rubella, varicella vaccine in healthy toddlers. Immunogenicity and Safety of Two Tetravalent (Measles, Mumps, Rubella, Varicella) Vaccines Coadministered With Hepatitis A and Pneumococcal Conjugate Vaccines to Children Twelve to Fourteen Months of Age Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles-mumps-rubella-varicella vaccine during the second year of life: An open, randomized controlled trial. Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting. Safety, immunogenicity and immediate pain of intramuscular versus subcutaneous administration of a measles–mumps–rubella–varicella vaccine to children aged 11–21 months Concomitant administration of varicella vaccine with combined measles, mumps, and rubella vaccine in healthy children aged 12 to 24 months of age. Evaluation of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials Safety and Immunogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine Coadministered With Measles-Mumps-Rubella-Varicella Vaccine in Children Aged 12 to 16 Months 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. Concomitant administration of hepatitis A vaccine with measles/mumps/rubella/varicella and pneumococcal vaccines in healthy 12- to 23-month-old children
This study was undertaken to assess the co-administration of an experimental measles-mumps-rubella-varicella vaccine ( MMRV , GlaxoSmithKline Biologicals ) with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate ( DTPa-HBV-IPV/Hib ) vaccine in healthy children . Healthy children aged 12–23 months ( N = 451 ) were r and omised to one of three parallel groups to receive one dose of MMRV vaccine co-administered with a booster dose of DTPa-HBV-IPV/Hib vaccine ( co-administration group ) , or one dose of MMRV vaccine alone ( MMRV group ) , or a booster dose of DTPa-HBV-IPV/Hib vaccine alone ( DTPa-HBV-IPV/Hib group ) . No differences in seroconversion rates for measles ( > 95 % ) , mumps ( > 80 % ) , rubella ( > 99 % ) and varicella ( > 98 % ) were seen between the co-administration group and the MMRV group . No differences in geometric mean titres ( GMTs ) were observed between the two groups with the exception of anti-measles titres , which were observed to be higher in the MMRV group than in the co-administration group ( 4,419.2 vs. 3,441.8 mIU/ml respectively ) . Immune response to the booster dose of DTPa-HBV-IPV/Hib vaccine was observed to be similar in the co-administration group and the DTPa-HBV-IPV/Hib group . Co-administration of the MMRV vaccine with a booster dose of DTPa-HBV-IPV/Hib vaccine was well-tolerated and did not exacerbate the reactogenicity profile of either vaccine . In summary , GlaxoSmithKline Biologicals ’ experimental MMRV vaccine was immunogenic and well-tolerated when administered with a booster dose of DTPa-HBV-IPV/Hib vaccine during the second year of life . The ability to co-administer the MMRV vaccine at the same time as other routine childhood immunisation vaccines could increase compliance with varicella vaccination in countries where this vaccine is already recommended and may facilitate implementation of varicella vaccination elsewhere Aim : This study evaluated the immunogenicity and safety of tetravalent measles-mumps-rubella-varicella ( MMRV ) vaccine produced with measles and rubella monovalent bulks derived from a newly established working seed virus stock ( MMRVnew WS ) compared with the combined MMRV vaccine derived from the current seed virus stock , in Taiwanese and Singaporean children ( NCT00892775 ) . Methods : Healthy children aged 11–22 mo were r and omized to receive two doses of either the MMRV new WS vaccine or the MMRV vaccine .  Antibody titers against measles , mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay . The primary objective was to demonstrate non-inferiority of MMRVnew WS to MMRV in terms of post-dose-1 seroconversion rates , defined as a group difference with a lower limit of the 95 % confidence interval greater than -10 % for each antigen . Parents/guardians recorded symptoms in diary cards for 43 d after each vaccine dose . Results : Non-inferiority of MMRV new WS to MMRV was achieved for all vaccine antigens . The lower limits of the 95 % confidence intervals for group differences ( MMRVnew WS group vs. MMRV ) for measles ( 99.4 % vs 100 % ) , mumps ( 89.7 % vs 90.4 % ) , rubella ( 99.7 % vs 100 % ) and varicella ( 97.6 % vs 92.9 % ) seroconversion rates were greater than -10 % . Mild symptoms including a peak in fever between days 5 and 12 , post-dose-1 , was observed in both groups . Conclusion : The immune responses elicited by the MMRV new WS vaccine were non-inferior to that elicited by the MMRV vaccine for all antigens . Both vaccines exhibited an acceptable safety profile in Taiwanese and Singaporean children In countries where routine varicella vaccination is implemented , it is usually given at the same age as that recommended for measles-mumps-rubella ( MMR ) vaccination . A combined multivalent measles-mumps-rubella-varicella ( MMRV ) vaccine would offer the convenience of a single injection and facilitate implementation of varicella vaccination into routine childhood immunisation schedules . We evaluated the immunogenicity and reactogenicity of a tetravalent MMRV c and i date vaccine compared to an extemporaneous mix of a measles-mumps-rubella vaccine and varicella vaccine ( MMR/V ) , and to a measles-mumps-rubella ( MMR ) vaccine alone . A multicentre study was conducted in which a total of 240 healthy children aged 12 months ( 80 per group ) were r and omised to receive MMRV , MMR/V , or MMR alone . Active surveillance for adverse events was undertaken for 43 days post-vaccination . Blood sample s were taken prior to vaccination and at 60 days post-vaccination . There were no significant differences between groups in rates of pain , redness , or swelling at the site of vaccination . There was no significant difference in the rate of any fever ( axillary temperature > or=37.5 degrees C ) and grade 3 fever ( axillary temperature > 39.0 degrees C ) between the groups receiving MMRV and MMR during the 43-day follow-up period . Although , a significant increase was found for fever of any cause with onset between days 0 and 14 for MMRV compared to the MMR group , there was no significant difference in grade 3 fever rates during the same period . With respect to immunogenicity , MMRV and MMR/V demonstrated similar seroconversion rates to each component compared to MMR alone , with at least 91.9 % of subjects in all groups seroconverting to each vaccine component 60 days after vaccination . Decreased GMTs for varicella antibody at day 60 indicated that there may have been inhibition of this response compared to MMR/V. This tetravalent MMRV c and i date vaccine showed promising results , although further examination of the possible increase in minor fever and decreased varicella immunogenicity should be assessed in future studies OBJECTIVE : We assessed the immunogenicity and safety of a combination measles , mump , rubella , and varicella vaccine ( MMRV ) ( ProQuad [ Merck & Co , Inc , West Point , PA ] ) administered to healthy children concomitantly with a pneumococcal 7-valent conjugate vaccine ( PCV-7 ) ( Prevnar [ Pfizer , Philadelphia , PA ] ) . PATIENTS AND METHODS : Healthy 12- to 15-month-old children who lacked vaccination and clinical histories for measles , mumps , rubella , varicella , and zoster but had written documentation of receipt of a 3-dose primary series of PCV-7  were r and omly assigned in a 2:1:1 ratio to receive either the MMRV and PCV-7 ( group 1 ) , PCV-7 followed 6 weeks later by MMRV ( group 2 ) , or MMRV followed 6 weeks later by PCV-7 ( group 3 ) . The primary safety analysis was 56 days ( 28 days after each visit ) . Immunogenicity was evaluated 6 weeks after each vaccination . RESULTS : A total of 1027 children were enrolled ( group 1 : 510 ; group 2 : 258 ; group 3 : 259 ) . For all 3 groups , the antibody response rate was ≥96.8 % for measles , mumps , and rubella , ≥88.0 % for varicella-zoster virus , and ≥98.3 % for all of the 7 Streptococcus pneumoniae serotypes . The immune responses to all antigens present in MMRV and PCV-7 were similar whether administered concomitantly or sequentially . The incidence of local and systemic adverse experiences ( AEs ) was comparable between group 1 and groups 2 and 3 combined . No vaccine-related serious AEs were reported . CONCLUSIONS : Concomitant administration of the MMRV and PCV-7 is highly immunogenic and generally well tolerated . Similar immune responses between the groups support concomitant administration of the MMRV and PCV-7 to healthy children 12 to 15 months of age 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 r and omized 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 , ∼12 months ; group 2 , ∼13.5 months ) . When the groups were matched for age , sample size was sufficient for comparison only in children ≥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 The objective was to study the incidence of febrile seizures prospect ively determined through age 4 years . A st and ardized r and omized cluster sample of nulliparous pregnant women from a geographically defined area were prospect ively followed from the beginning of pregnancy through the child 's age 4 . Data on children eligible for the study ( n = 1287 ) , including febrile seizures , sociodemographic data , developmental milestones , and chronic diseases , were prospect ively collected from families and health care staff . Data were available for 1033 children . Through age 4 , the average annual incidence of febrile seizures was 14 per 1000 person-years ( 15 for girls and 13.5 for boys ) . The incidence rate through age 4 was 6.9 % ( 7.3 % for girls and 6.5 % for boys ) . The incidence rate of febrile seizures in Finnish children is comparable to that reported previously . The higher figure , based on prospect i ve rather than retrospective data , may give a more accurate picture of the clinical importance of febrile seizures Background : 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 . Methods : This open-label , multicenter clinical trial ( clinical trials.gov identifier NCT00560755 ) was design ed 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 . Results : 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 . Conclusion : The results confirm the good safety profiles of MMRV and of measles , mumps and rubella vaccines manufactured with recombinant human albumin BACKGROUND Rates of varicella have decreased substantially in countries implementing routine varicella vaccination . Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine ( MMRV ) . We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV . METHODS This study was done in ten European countries with endemic varicella . Healthy children aged 12 - 22 months were r and omised ( 3:3:1 ratio , by computer-generated r and omisation list , with block size seven ) to receive 42 days apart ( 1 ) two doses of MMRV ( MMRV group ) , or ( 2 ) MMR at dose one and monovalent varicella vaccine at dose two ( MMR+V group ) , or ( 3 ) two doses of MMR ( MMR group ; control ) . Participants and their parents or guardians , individuals involved in assessment of any outcome , and sponsor staff involved in review or analysis of data were masked to treatment assignment . The primary efficacy endpoint was occurrence of confirmed varicella ( by detection of varicella zoster virus DNA or epidemiological link ) from 42 days after the second vaccine dose to the end of the first phase of the trial . Cases were grade d for severity . Efficacy analyses were per protocol . Safety analyses included all participants who received at least one vaccine dose . This trial is registered with Clinical Trials.gov , number NCT00226499 . FINDINGS Between Sept 1 , 2005 , and May 10 , 2006 , 5803 children ( mean age 14·2 months , SD 2·5 ) were vaccinated . In the efficacy cohort of 5285 children , the mean duration of follow-up in the MMRV group was 36 months ( SD 8·8 ) , in the MMR+V group was 36 months ( 8·5 ) and in the MMR group was 35 months ( 8·9 ) . Varicella cases were confirmed for 37 participants in the MMRV group ( two moderate to severe ) , 243 in the MMR+V group , and 201 in the MMR group . Second cases occurred for three participants ( all in the MMR+V group ) . Varicella cases were moderate to severe for two participants in the MMRV group , 37 in the MMR+V group ( one being a second case that followed a mild first case ) ; and 117 in the  MMR group . Efficacy of two-dose MMRV against all varicella was 94·9 % ( 97·5 % CI 92·4 - 96·6 ) , and against moderate to severe varicella was 99·5 % ( 97·5 - 99·9 ) . Efficacy of one-dose varicella vaccine against all varicella was 65·4 % ( 57·2 - 72·1 ) , and against moderate to severe varicella ( post hoc ) was 90·7 % ( 85·9 - 93·9 ) . The most common adverse event in all groups was injection-site redness ( up to 25 % of participants ) . Within 15 days after dose one , 57·4 % ( 95 % CI 53·9 - 60·9 ) of participants in the MMRV group reported fever of 38 ° C or more , by contrast with 44·5 % ( 41·0 - 48·1 ) with MMR+V , and 39·8 % ( 33·8 - 46·1 ) with MMR . Eight serious adverse events were deemed related to vaccination ( three MMRV , four MMR+V , one MMR ) . All resolved within the study period . INTERPRETATION These results support the implementation of two-dose varicella vaccination on a short course , to ensure optimum protection from all forms of varicella disease . FUNDING GlaxoSmithKline Vaccines Background : This open , r and omized , controlled study [ 208136/018 ] assessed the safety and immunogenicity of early vaccination with an experimental tetravalent measlesmumps-rubella-varicella ( MMRV ) vaccine ( GlaxoSmithKline Biologicals ) compared to concomitant administration of separate licensed MMR ( Priorix ™ ) and varicella ( Varilrix ™ ) vaccines ( MMR+V ) . Methods : Vaccines were administered as a two-dose course in healthy children at 9 and 12 months of age ( N = 153 in the MMRV group and N = 146 in the MMR+V group ) . Results : The incidence of fever of any intensity ( axillary temperature ≥ 37.5 ° C ) during the 15 days of follow-up post-dose 1 was higher in the MMRV group than in the MMR+V group ( 48.3 % vs 25.7 % , respectively ) but was low in both groups post-dose 2 ( 20.3 % and 22.1 % , respectively ) . The incidence of fever > 39.0 ° C and the incidence of solicited local symptoms ( pain , redness , swelling ) were low ( ≤ 5.3 % and ≤ 13.7 % , respectively ) in the two groups after each vaccine dose . Seroconversion rates were similar in the two groups for all vaccine antigens after each vaccine dose and were ≥ 99.2 % for each antigen post-dose 2 . Anti-measles GMT was higher in the MMRV group than in the MMR+V group after the first vaccine dose . After the second dose , slight to moderate increases in measles , mumps and rubella antibody titers and a substantial increase in varicella antibody titer were seen in both groups , leading to higher GMTs in the MMRV group compared with the MMR+V group for measles , mumps and varicella . Anti-rubella antibody GMTs were similar in the two groups post-dose 2 . Conclusion : Early vaccination with two doses of this experimental MMRV vaccine at 9 and 12 months of age was well-tolerated and at least as immunogenic as two doses of separate licensed MMR and varicella vaccines BACKGROUND Invasive meningococcal disease can have devastating outcomes , especially in high-risk groups such as infants . As infants are recommended to receive multiple vaccines during a single office visit , this phase 3 study assessed the safety and immune response to MenACWY-CRM at alternative visits in older infants and concomitant use with measles , mumps , rubella , varicella vaccine ( MMRV ) at 12 months of age . METHODS Two age groups were concurrently enrolled : 7- to 9-month-old infants who received 2 doses of MenACWY-CRM at 7 - 9 and 12 months and were r and omized 1:1 to receive MenACWY-CRM with or without MMRV at 12 months , and 12-month-old infants who received MMRV only at 12 months . Using predefined non-inferiority criteria , immune responses to the antigens in MMRV were compared between those who did and did not receive MenACWY-CRM ; immune responses to MenACWY-CRM as measured by the percentage of subjects with human serum bactericidal activity ( hSBA ) titers ≥ 8 , were compared between those who did and did not receive concomitant MMRV . Adequacy of the immune response to 2 doses of MenACWY-CRM administered at 7 - 9 and 12 months was also assessed . Local and systemic reactions , adverse events result ing in withdrawal or requiring medical attention and serious adverse events were monitored . RESULTS Concomitant administration of MMRV with MenACWY-CRM did not affect the immune response to either vaccine . The 2-dose series of MenACWY-CRM induced adequate immune response to all 4 serogroups . No increased reactogenicity was observed with MenACWY-CRM+MMRV compared with MMRV alone , and there were no study -related serious adverse events . CONCLUSIONS Concomitant administration of MenACWY-CRM with MMRV vaccinations at 12 months was well-tolerated , without safety concerns . Robust immune responses to all components of both vaccines were produced and all criteria for non-inferiority were met , supporting the use of a 2-dose regimen of MenACWY-CRM in this age group Background : This study compared single-dose tetravalent measles , mumps , rubella , varicella vaccine , Priorix-Tetra , stored refrigerated ( GSK+4C ) or frozen ( GSK-20C ) , with ProQuad ( Merck-20C ) , when coadministered with hepatitis A vaccine ( HAV ) and 7-valent pneumococcal conjugate vaccine ( PCV7 ) . Methods : Multicenter , observer-blind phase 2 study in 1783 healthy 12–14 month olds r and omized to : GSK+4C ( n = 705 ) , GSK-20C ( n = 689 ) or Merck-20C ( n = 389 ) , administered concomitantly with HAV ( Havrix ) and PCV7 ( Prevnar )  .  Seroresponse rates and antibody geometric mean concentrations/titers were determined from enzyme-linked immunosorbent assay and neutralization assays . Reactogenicity and safety were assessed . Results : Seroresponse rates ( day 42 ) were > 97 % for measles and rubella viruses and > 92 % for mumps virus , in all groups . Noninferiority of both GSK+4C and GSK-20C vaccines versus Merck-20C was demonstrated for seroresponse rates to measles , mumps and rubella viruses ( lower 97.5 % confidence interval above −5 % , −10 % and −5 % , respectively ) . For varicella-zoster virus , seroresponse rates were 57.1 % , 69.8 % and 86.7 % in the GSK+4C , GSK-20C and Merck-20C groups , respectively . Noninferiority was not shown for either GSK vaccine ( lower 97.5 % confidence intervals < −15 % ) . Geometric mean concentration ratios for anti-varicella-zoster virus demonstrated noninferiority ( lower 97.5 % confidence interval ≥0.5 ) versus Merck-20C for GSK-20C only . Geometric mean concentration ratios for antibodies to HAV and to PCV7 pneumococcal serotypes also met criteria for noninferiority for both GSK groups compared with Merck-20C . GSK vaccine safety was observed comparable to Merck-20C . Localized but not generalized measles/rubella-like rash and grade 3 fever was reported slightly more frequently with GSK vaccines , but antipyretic use was similar . The incidence of subjects experiencing at least 1 serious adverse event was 2.0 % , 2.9 % and 1.8 % in the GSK+4C , GSK-20C and Merck-20C groups , respectively . Conclusions : Noninferiority of both GSK measles , mumps , rubella , varicella vaccines versus Merck-20C was demonstrated for responses to measles , mumps and rubella viruses but was not fully demonstrated for varicella-zoster virus . The vaccines showed acceptable reactogenicity/safety when coadministered with HAV and PCV7 Co-administration of meningococcal ACWY-tetanus toxoid conjugate vaccine ( ACWY-TT ) with MMRV vaccine was investigated in 1000 12 - 23-month old children r and omized ( 3:3:1:1 ) to receive co-administered ACWY-TT+MMRV , or a single dose of ACWY-TT , MMRV or MenC-CRM(197 ) . Non-inferiority of ACWY-TT to MenC-CRM(197 ) and non-inferiority of ACWY-TT+MMRV to ACWY-TT and MMRV alone , and the immunogenicity of serogroups AWY were demonstrated according to pre-defined criteria . Fever reactions in ACWY+MMRV and MMRV groups were comparable . ACWY-TT can be co-administered with MMRV without affecting immunogenicity or safety profiles of either vaccine . This study has been registered at www . clinical trials.gov NCT00474266 BACKGROUND A combined measles , mumps , rubella , varicella live vaccine ( MMRV , Merck and Co. , Inc. , US ) was recently licensed in the US . Pre-licensure clinical trial data showed a significant increase in fever in days 5 - 12 following MMRV vaccination as compared to the vaccines given separately ( MMR+V ) . This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV . METHODS Children ages 12 - 60 months who received a first dose of MMRV in February 2006-June 2007 in a managed care organization were included in the study . Subjects were optimally matched on age , sex , and calendar date of vaccination to children who received MMR+V concomitantly in November 2003-January 2006 , before MMRV licensure . Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel , according to pre-specified criteria . RESULTS During the 30 days post-vaccination , there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR+V cohorts , respectively . After review of available medical charts and adjudication , there were 84 cases of confirmed febrile convulsion , 44 ( 1.41/1000 ) and 40 ( 1.28/1000 ) in the MMRV and MMR+V cohorts , respectively ( RR=1.10 , 95 % CI=0.72 , 1.69 ) . In days 5 - 12 following vaccination , a pre-specified period of interest , the respective numbers were 22 ( 0.70/1000 ) and 10 ( 0.32/1000 ) ( RR=2.20 , 95 % CI=1.04 , 4.65 ) . CONCLUSION These data suggest that the risk of febrile convulsion is increased in days 5 - 12 following vaccination with MMRV as compared to MMR+V given separately during the same visit , when post-vaccination fever and rash are also increased in clinical trials . While there was no evidence of an increase in the overall month following vaccination , the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine This study compared intramuscular and subcutaneous administration of two doses of measles – mumps – rubella – varicella ( MMRV ) combination vaccine ( Priorix-Tetra ™ , GlaxoSmithKline Biologicals ) in children . Healthy children ( N = 328 ) were r and omised to receive  MMRV  either intramuscularly or subcutaneously . Reactogenicity was similar between treatment groups for immediate vaccination pain , vaccination site pain , redness and incidence of fever and rashes . Slightly less vaccination site swelling occurred during days 0–3 of the post-vaccination period after intramuscular administration . Seroconversion rates for all components , 42–56 days post-dose 2 , ranged from 99.3 % to 100 % in the intramuscular group and from 98.6 % to 100 % in the subcutaneous . Cell-mediated immunity data supported the humoral immunogenicity findings . In summary , the MMRV vaccine is well tolerated and highly immunogenic when administered either subcutaneously or intramuscularly to children in the second year of life The reactogenicity and immunogenicity of three combined measles , mumps and rubella ( MMR ) vaccines and one administered with a varicella vaccine was studied in infants . The vaccines were Priorix ( design ated MeMuRu , Group 1 ) , M-M-R II ( Group 2 ) , Triviraten ( Group 3 ) and Priorix + a varicella vaccine , Varilrix ( Group 4 ) . Fever was greater in Group 2 ( 61.3 % ) compared to Group 1 ( 48.5 % ; p = 0.033 ) or Group 3 ( 37.1 % ; p = 0.009 ) . Rash with fever was reported in Group 2 ( 4.8 % ) and Group 4 ( 3.3 % ) , but not for Group 1 . Anti-measles , -mumps and -rubella seroconversion was similar for Group 1 ( 96.1 % , 96.1 % and 100 % , respectively ) , Group 4 ( 98 % for all three ) , and Group 2 ( 91.5 % , 93.6 % and 97.9 % ) 60 days post-vaccination . GMTs for measles ( 3,053.7 - 3,412.2 mIU/ml ) , mumps ( 1,001.5 - 1,158.8 U/ml ) and rubella ( 68.7 - 89.1 IU/ml ) were similar for Groups 1 , 2 and 4 at Day 60 . Antibody persistence was noted 2 years post-vaccination . The MeMuRu + varicella combination showed no clinical ly relevant increase in reactogenicity and should facilitate introduction of a varicella vaccine into national immunization schedules 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 r and omized to receive either MMRV and placebo or M-M-R ® II and VARIVAX . Injections were given concomitantly at separate sites . Subjects r and omized 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-R ® II 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-R ® II 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-R ® II and VARIVAX administered concomitantly BACKGROUND Meningococcal serogroup B disease disproportionately affects infants . We assessed lot-to-lot consistency , safety and immunogenicity , and the effect of concomitant vaccination on responses to routine vaccines of an investigational multicomponent vaccine ( 4CMenB ) in this population . METHODS We did primary and booster phase 3 studies between March 31 , 2008 , and Aug 16 , 2010 , in 70 sites in Europe . We used two series of sponsor-supplied , computer-generated r and omisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations ( diphtheria-tetanus-acellular pertussis , inactivated poliovirus , hepatitis B plus Haemophilus influenzae type b , and seven-valent pneumococcal vaccine ) at 2 , 4 , and 6 months of age alone , or concomitantly with 4CMenB or serogroup C conjugate vaccine ( MenC ) in : 1 ) an open-label , lot-to-lot immunogenicity and safety sub study of three 4CMenB lots compared with routine vaccines alone ( 1:1:1:1 , block size eight ) ; or 2 ) an observer-blind , lot-to-lot safety sub study of three 4CMenB lots compared with MenC ( 1:1:1:3 , block size six ) . At 12 months , 4CMenB-primed children from either sub study were r and omised ( 1:1 , block size two ) to receive 4CMenB booster , with or without measles-mumps-rubella-varicella ( MMRV ) vaccine . Immunogenicity was assessed by serum bactericidal assay with human complement ( hSBA ) against serogroup B test strains , and on r and omly selected subsets of serum sample s for routine vaccines ; laboratory personnel were masked to assignment . The first co primary outcome was lot-to-lot consistency ( hSBA geometric mean ratio of all lots between 0·5 and 2·0 ) , and the second was an immune response ( hSBA titre ≥5 ) for each of the three strains . The primary outcome for the booster study was immune response to booster dose . Immunogenicity data for 4CMenB were for the modified intention-to-treat population , including all infants from the open-label sub study who provided serum sample s. The safety population included all participants who contributed safety data after at least one dose of study vaccine . These trials are registered with Clinical Trials.gov , numbers NCT00657709 and NCT00847145 . FINDINGS We enrolled 2627 infants in the open-label phase , 1003 in the observer-blind phase , and 1555 in the booster study . Lot-to-lot consistency was shown for the three 4CMenB lots , with the lowest 95 % lower confidence limit being 0·74 and the highest upper limit being 1·33 . Of 1181–1184 infants tested 1 month after three 4CMenB doses ( all lots pooled ) , 100 % ( 95 % CI 99–100 ) had hSBA titres of 5 or more against strains selective for factor H binding protein and neisserial adhesin A , and 84 % ( 82–86 ) for New Zeal and outer-membrane vesicle . In a subset ( n=100 ) , 84 % ( 75–91 ) of infants had hSBA titres of 5 or more against neisseria heparin binding antigen . At 12 months of age , waning titres were boosted by a fourth dose , such that 95–100 % of children had hSBA titres of 5 or more for all antigens , with or without concomitant MMRV . Immune responses to routine vaccines were much the same with or without concomitant 4CMenB , but concomitant vaccination was associated with increased reactogenicity . 77 % ( 1912 of 2478 ) of infants had fever of 38·5 ° C or higher after any 4CMenB dose , compared with 45 % ( 295 of 659 ) after routine vaccines alone and 47 % ( 228 of 490 ) with MenC , but only two febrile seizures were deemed probably related to 4CMenB. INTERPRETATION 4CMenB is immunogenic in infants and children aged 12 months with no clinical ly relevant interference with routine vaccines , but increases reactogenicity when administered concomitantly with routine vaccines . This breakthrough vaccine offers an innovative solution to the major remaining cause of bacterial meningitis in infant and toddlers . FUNDING Novartis Vaccines and Diagnostics Background : A booster dose of pneumococcal conjugate vaccine may be administered at the same age as measles-mumps-rubella-varicella ( MMRV ) vaccination . This study examined the safety , reactogenicity , and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) when coadministered with MMRV vaccine . Methods : In this open , controlled study , 325 healthy children aged 12 to 14 months were r and omized to 1 of 3 groups : the first group ( N = 110 ) received PHiD-CV and MMRV vaccine followed 6 to 8 weeks later by MMRV and DTPa-HBV-IPV/Hib vaccines ; the second group ( N = 101 ) received DTPa-HBV-IPV/Hib and MMRV vaccines followed 6 to 8 weeks later by PHiD-CV and MMRV vaccine ; the third group ( N = 114 ) received PHiD-CV and DTPa-HBV-IPV/Hib vaccine during 1 vaccination visit . Immune responses were assessed with GlaxoSmithKline 's 22F-inhibition enzyme-linked immunosorbent assay ( for PHiD-CV ) , commercial enzyme-linked immunosorbent assay ( for MMR ) , or indirect immunofluorescence assay ( for varicella ) . Adverse events were recorded by the parents/guardians . Results : After the first vaccination , 2 peaks in fever ( rectal temperature ≥38 ° C ) were observed ; at days 0 to 2 , related to PHiD-CV and DTPa-HBV-IPV/Hib vaccination , and at days 4 to 12 , related to MMRV vaccination . Booster responses to pneumococcal antigens and protein D and seroconversion rates for all MMRV vaccine components were high . Conclusions : PHiD-CV and MMRV vaccine can be coadministered without compromising the safety and immunogenicity profiles of either vaccine 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 Exp and ed 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 , r and omised , 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 This open-label , multicenter , r and omized , comparative study evaluated immunogenicity , safety and tolerability of  concomitant ( Group 1 ; n = 330 ) vs. non-concomitant ( Group 2 ; n = 323 ) VAQTA ™ ( 25U/0.5 mL ) ( hepatitis A vaccine ; HAV ) with ProQuad ™ ( measles/mumps/rubella/varicella ; MMRV ) and Prevnar ™ ( 7-valent pneumococcal ; PCV-7 ) in healthy , 12–23 mo old children . Group 1 received HAV/MMRV/PCV-7 concomitantly on Day 1 and second doses of HAV/MMRV at Week 24 . Group 2 received MMRV/PCV-7 on Day 1 , HAV at Weeks 6 and 30 and MMRV at Week 34 . Hepatitis A seropositivity rate ( SPR : ≥10 mIU/mL ; 4 weeks postdose 2 ) , varicella zoster-virus ( VZV ) SPR ( ≥5 gpELISA units/mL ) and geometric mean titers ( GMT ) to S. pneumoniae were examined . Injection-site and systemic adverse experiences ( AEs ) and daily temperatures were collected . Hepatitis A SPR were 100 % for Group 1 and 99.4 % for Group 2 after two HAV doses ; risk difference = 0.7 ( 95%CI : −1.4,3.8 , non-inferior ) regardless of initial serostatus . VZV SPR was 93.3 % for Group 1 and 98.3 % for Group 2 ; risk difference = −5.1 ( 95%CI : −9.3,−1.4 ; non-inferior ) . S. pneumoniae GMT fold-difference ( 7 serotypes ) ranged from 0.9 to 1.1 ; non-inferior . No statistically significant differences in the incidence of individual AEs were seen when HAV was administered concomitantly vs. non-concomitantly . Three ( all Group 2 post-administration of MMRV/PCV-7 ) of 11 serious AEs were considered possibly vaccine-related : dehydration and gastroenteritis ( same subject ) on Day 52 ; febrile seizure on Day 9 . No deaths were reported . Antibody responses to each vaccine given concomitantly were non-inferior to HAV given non-concomitantly with MMRV and PCV-7 . Administration of HAV with PCV-7 and MMRV had an acceptable safety profile in 12- to 23-mo-old children
BACKGROUND Considering the febrile seizure rate , there is no longer a clear preference for use of measles-mumps-rubella-varicella ( MMRV ) vaccine over separate measles-mumps-rubella ( MMR ) and varicella ( V ) vaccine .
This work was undertaken to assess the risk of  febrile seizure after MMRV vaccine in children .