Long term (24 months) follow-up of a hepatitis A and B vaccine, comparing a two and three dose schedule in adolescents aged 12-15 years. A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: an open, randomised, controlled trial. A two-dose combined vaccine against hepatitis A and hepatitis B in healthy children and adolescents compared to the corresponding monovalent vaccines. Hepatitis A/B vaccination of adults over 40 years old: comparison of three vaccine regimens and effect of influencing factors. Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine. Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience. Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study. Hepatitis B Vaccination in HIV-Infected Youth: A Randomized Trial of Three Regimens Randomized Trial to Determine Safety and Immunogenicity of Two Strategies for Hepatitis B Vaccination in Healthy Urban Adolescents in the United States Response to challenge dose among young adults vaccinated for hepatitis B as infants: importance of detectable residual antibody to hepatitis B surface antigen. Antibody persistence and immune memory elicited by combined hepatitis A and B vaccination in older adults. Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children. Immunogenicity and reactogenicity of a combined hepatitis A-hepatitis B vaccine in adolescents. Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls. Comparative immunogenicity of two vaccination schedules of a combined hepatitis A and B vaccine in healthy volunteers. A new accelerated vaccination schedule for rapid protection against hepatitis A and B. Comparative evaluation of the immunogenicity of combined hepatitis A and B vaccine by a prospective and retrospective trial Reactogenicity profile of a combined hepatitis A and B vaccine in clinical practice: a naturalistic study in adult travellers. Clinical and immunological investigation of a new combined hepatitis A and hepatitis B vaccine. Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months. Hepatitis A and hepatitis B vaccinations: immunogenicity of combined vaccine and of simultaneously or separately applied single vaccines. Rapid and sustained immune response against hepatitis A and B achieved with combined vaccine using an accelerated administration schedule. Immunogenicity of a combined hepatitis A and B vaccine in healthy young adults. A two dose schedule for combined hepatitis A and hepatitis B vaccination in children ages one to eleven years. Comparison of long-term (10 years) immunogenicity of two- and three-dose regimens of a combined hepatitis A and B vaccine in adolescents. Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults. A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B) in adults. Immunogenicity of an accelerated vaccination regime with a combined hepatitis a/b vaccine in patients with chronic hepatitis C. A two dose combined hepatitis A and B vaccine in Chinese youngsters. Simultaneous vaccination against hepatitis A and B: results of an open, randomized study from the occupational health point of view. Immunogenicity and reactogenicity of a combined hepatitis A and B vaccine in young adults. Evaluation of immune responses to combined hepatitis A and B vaccine in HIV-infected children and children on immunosuppressive medication.
BACKGROUND A two dose schedule ( 0 and 6 months ) for a combined hepatitis A and B vaccine is currently being developed . METHODS The present study compared the combined hepatitis A and B vaccines in 12 - 15-year-old : Twinrix paediatric ( 360 EL.U HAV antigen/10 microg HBs antigen ) on a three dose schedule ( 0 , 1 and 6 months ) to the adult formulation ( 720 EL.U HAV antigen/20 microg HBs antigen ) on a two dose schedule ( 0 and 6 months ) and also reports on the follow-up until 24 months . RESULTS Seroconversion ( SC ) rates to HAV in both regimens reached 100 % by month 7 and remained 100 % up to month 24 . Anti-HAV , GMTs were slightly higher for the two dose than the three dose regimens at this time point . Seroprotection against hepatitis B was > 99 % in both groups by month 7 and 24 , this was still 94 and 96 % , respectively . Statistical non-inferiority of group 1 ( two dose ) versus group 2 ( three dose ) was demonstrated . All vaccines were well tolerated and the most frequently reported local and general symptoms were pain and fatigue . There were no vaccine-related serious adverse events reported during the study . CONCLUSION The two dose regimen elicited similar immunogenicity to HAV and HBsAg and reactogenicity profiles as the three dose regimen in this group of healthy adolescents . The reduction in the number of doses from the current three dose schedule will make vaccination against hepatitis A and B more convenient to the vaccinee , reduce healthcare staff time required and may lower the overall costs associated with vaccination The co-administration of the tetravalent meningococcal conjugate vaccine , MenACWY-TT , with a licensed hepatitis A and B vaccine , HepA/B ( Twinrix ( ® ) ) , was compared to their separate administration in this open , r and omised , controlled study . Healthy subjects 11 - 17 years of age ( n=611 ) were r and omised ( 3:1:1 ) to receive both vaccines , MenACWY-TT alone or HepA/B alone . The co-administration of both vaccines was shown to be non-inferior to their individual administration . At seven months after the first vaccination , 99.4 - 100 % of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1 % of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity , safety and reactogenicity of either of the vaccines BACKGROUND Immunization against hepatitis A and B has been available for some time , protecting against both infections . With a view to achieving further reduction in the number of interventions and increasing convenience of the vaccinee , we investigated the reactogenicity and immunogenicity of a combined hepatitis A and B vaccine in healthy 4- to 20-year-old subjects at a 0 , 6-month schedule . METHODS Two hundred forty-eight study subjects were allocated to two study groups and received either two doses of the combined hepatitis A and B vaccine ( 68 % of subjects ) or the corresponding monovalent hepatitis A and hepatitis B vaccines ( 32 % of subjects ) concomitantly in opposite arms . Reactogenicity was assessed via diary cards after each vaccination . Serum sample s were analyzed at months 1 , 2 , 6 , and 7 . RESULTS All vaccines were well tolerated and very few symptoms were scored as severe . All but one subject seroconverted for anti-hepatitis A virus ( anti-HAV ) antibodies ( 98.6 % ) and 100 % of subjects seroconverted for anti-hepatitis B ( HBs ) antibodies , with respective seroprotection rates of 98.7 % for the combined vaccine group and 95.9 % for the concomitant vaccine group ( p > 0.05 ) , respectively . Geometric mean titers were higher in the group receiving the combined vaccine : 6,635 mIU/mL vs. 2,728 mIU/mL ( p = 0.0001 ) for anti-HAV and 3,362 mIU/mL vs. 1,724 mIU/mL ( p = 0.0205 ) for anti-HBs , respectively . Younger subjects had a stronger immune response compared to older subjects . CONCLUSIONS The combined hepatitis A and B vaccine was well tolerated at this two-dose schedule . The combined vaccine had higher immunogenicity , probably explained by a adjuvant effect of the antigens . Vaccination programs requiring fewer injections will most likely have a positive impact on compliance rate and comfort of the vaccinee Challenged by contrasting data on low immune responses in the elderly with a combined hepatitis A/B vaccine  , a r and omised , controlled study was conducted to assess the immunogenicity of three hepatitis A and B vaccination regimens ( group 1 : combined hepatitis A/B vaccine Twinrix [ GSK ] ; group 2 : co-administered hepatitis A vaccine , Havrix [GSK]+hepatitis B vaccine Engerix -B [ GSK ] , group 3 : co-administered hepatitis A vaccine , Vaqta [ Sanofi-Pasteur MSD]+hepatitis B vaccine HB VAX PRO [ Sanofi-Pasteur MSD ] ) and the effect of influencing factors in subjects > 40 years . On completion of the full vaccination course , anti-HBs seroprotection ( SP ) rates were 92 , 80 and 71 % in groups 1 , 2 and 3 , respectively ; anti-HAV seropositivity ( S+ ) rates were 97 , 99 and 99 % , respectively . In group 1 , anti-HBs SP rate was non-inferior as well as superior and anti-HAV S+ rate was non-inferior to that in groups 2 and 3 . Anti-HBs response was most significantly influenced by the vaccine regimen , followed by age , gender and BMI ( stepwise multiple regression analysis ) . BMI had the most significant influence on HAV response followed by age , gender and vaccine regimen . In conclusion , Twinrix induced superior hepatitis B SP rates and similar hepatitis A S+ rates compared to concomitant administration of monovalent vaccines in subjects aged > 40 years A r and omized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety , tolerability , and immunogenicity .  Healthy volunteers > /=11 years of age were divided into 4 groups . Each of 3 groups received a separate consistency lot of the combination vaccine , and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines . Injections were given at weeks 0 and 24 . The combination vaccine was generally well tolerated . The hepatitis A portion of the combination vaccine produced clinical ly acceptable high seropositivity rates 4 and 52 weeks after the first injection . The hepatitis B portion of the vaccine did not produce clinical ly acceptable seropositivity rates 4 weeks after the second injection . Lack of antibody production may be attributed , at least in part , to immunologic interference The immunogenicity of three currently used hepatitis B vaccines was compared in an unselected study population in an every day travel clinical setting . Five hundred and eighteen vaccinees received Engerix-B ( EB ) , 990 received Twinrix ( TWX ) , and  366 were immunised with Gen-HB-Vax ( GHB ) . Overall , 88.6 % of the vaccinees , tested within the first 6 months after completion of the vaccination series , developed protective levels of anti-HBs ( > or = 10 mIU/ml ) . However , GHB recipients showed significantly lower seroprotection rates ( SPR ) than EB and TWX recipients ( 79.3 % vs. 87.7 % vs. 92.3 % , P < 0.000001 ) . GMTs for anti-HBs , tested within 6 months after the third vaccination , showed the lowest results in the GHB group , followed by EB and TWX ( 142 vs. 523 vs. 1008 mIU/ml , P < 0.000001 ) . TWX vaccinees , however , showing a higher antibody decline rate than EB recipients within the first years after completion of the full immunisation course ( 30 % vs. 25 % ; P = 0.0538 ) . This study confirms an overall good immune response to the 20 microg-dose vaccine , in the course of a regular clinical setting . The significant difference in SPRs and GMTs to the 10 microg-dose vaccine , however , may influence future immunisation practice s for the elderly An open , r and omised study was undertaken to demonstrate the equivalence in immunogenicity and to determine the reactogenicity and safety of two dosing schedules ( 0 , 6 or 0 , 12 month ) of an adult formulation of a combined hepatitis A and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20 microg of hepatitis B surface antigen ( Twinrix , SmithKline Beecham Biologicals , Belgium ) in 240 healthy volunteers aged 12 - 15 years . The vaccine was well tolerated when administered using either vaccination schedule . At month 7 , 98.1 % of subjects completing the 0 , 6 month vaccination schedule were seroprotected against hepatitis B ( anti-hepatitis B surface antigen ( anti-HBs ) > or = 10 mIU/ml ) and 100 % were seropositive for anti-hepatitis A virus ( anti-HAV ) antibodies ( i.e. , > or = 33 mIU/ml ) . The corresponding geometric mean titres ( GMTs ) were 2791 mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies . At month 13 , 97 % of subjects assigned to the 0 , 12 month vaccination schedule were protected against hepatitis B and 99 % were seropositive for anti-HAV antibodies . The corresponding GMTs were 4340 and 8472 mIU/ml , respectively . A combined response ( i.e. , subjects , who were seropositive for anti-HAV antibodies and seroprotected for anti-HBs antibodies ) was achieved in 98 % of subjects vaccinated according to the 0 , 6 month interval and in 96 % of subjects vaccinated using the 0 , 12 month schedule . The reactogenicity of both vaccination schedules was also equivalent . The results thus show that the combined hepatitis A and B vaccine can be administered using flexible vaccination intervals , which make it suitable for use in large-scale hepatitis immunisation programmes Background : HIV-infected youth are at risk of hepatitis B infection and should be vaccinated . Previous reports suggest reduced response to st and ard hepatitis B vaccine regimens . Methods : HIV-infected youth , aged 12 to younger than 25 years , were r and omly assigned to one of three treatment arms : Arm 1 : Engerix B , 20 μg HBsAg ; Arm 2 : Engerix B ( GlaxoSmithKline , Rixensart , Belgium ) , 40 μg ; and Arm 3 : Twinrix ( GlaxoSmithKline , Rixensart , Belgium ) , 20 μg HBsAg combined with 720 ELU hepatitis A antigen . Vaccines were administered at Weeks 0 , 4 , and 24 . Results : Characteristics of evaluable patients ( n = 336 ) at entry were similar in the study arms . At enrollment , median CD4 + T-cell count was 460 cells/mm3 ( interquartile range , 305 - 668 ) ; 13 % were less than 200 cells/mm3 . Among Engerix B , 20-μg recipients , 60.4 % responded to vaccine ( HBsAb 10 IU/mL or greater at Week 28 ) . Improved vaccine response was seen in recipients of Engerix B , 40 μg ( 73.2 % versus Arm 1 , P = 0.04 ) and Twinrix ( 75.4 % versus Arm 1 , P = 0.02 ) . In multivariate analysis , only baseline CD4 + T-cell count and study arm were independent predictors of vaccine response . Conclusions : In HIV-infected youth , a three-dose vaccination regimen with Engerix B , 40 μg , or Twinrix and higher baseline CD4 + T-cell counts were independently associated with improved vaccine response Background : Multiple studies have shown excellent response rates after hepatitis B immunization in youth ; however , one previous study conducted in urban youth demonstrated poor responses . Methods : Urban youth , ages 12 to 17 years , at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical / Research sites were r and omized to receive either 2 doses of Recombivax HB ( 10 & mgr;g hepatitis B surface antigen ) or Twinrix ( 20 & mgr;g hepatitis B surface antigen and 720 EL.U hepatitis A antigen ) at 0 and 24 weeks . Safety data were collected and antibody measures performed at 0 , 28 , and 76 weeks . Results : A total of 123 subjects were enrolled and 102 had week 28 serum sample s available for antibody measure . A positive response ( serum antibody ≥10 mIU/mL ) to hepatitis B antigen was documented in 41 of 47 ( 87.2 % ; 95 % confidence interval [ CI ] 74.3%–95.2 % ) Recombivax HB recipients and in 52 of 55 ( 94.6 % ; 95 % CI , 84.9%–98.9 % ) Twinrix recipients ( P = 0.295 ) . In an adjusted analysis , those identified as Hispanic ethnicity ( N = 86 ) were more likely to have a positive response ( odds ratio 7.38 , 95 % CI , 1.56–34.95 ; P = 0.0018 ) ; whereas those who identified as not heterosexual ( N = 9 ) were less likely to respond ( odds ratio = 0.12 , 95 % CI , 0.02–0.74 ) . The majority of youth in the Twinrix arm were hepatitis A antibody positive at baseline ( 26/51 ; 51 % ) ; however , 24 of 25 hepatitis A antibody negative youth responded to the hepatitis A component . Both vaccines were safe . Conclusions : Response rate to 2 doses of Recombivax HB in urban youth is lower than previous studies suggest . The factors associated with diminished response are not known OBJECTIVE To determine whether a difference in antibody to hepatitis B surface antigen ( anti-HBs ) response to a hepatitis B vaccine challenge dose existed among persons with a baseline anti-HBs level of 0 mIU/mL ( group 1 ) and those with " non-zero " levels of 0.1 - 4.9 ( group 2 ) and 5.0 - 9.9 ( group 3 ) mIU/mL , according to the VITROS ECi anti-HBs assay . DESIGN Sub analysis of r and omized clinical trial . Response was defined as a postchallenge anti-HBs level of at least 10 mIU/mL and 4-fold rise in anti-HBs level 2 weeks after a single challenge dose of 10 vs 20 µg Engerix-B. Baseline was defined as the anti-HBs level immediately before administration of the challenge dose . SETTING Pediatric integrated healthcare system near Houston , Texas . PARTICIPANTS Three hundred nineteen US-born 16 - 19-year-olds who completed the hepatitis B vaccine series during the first year of life . RESULTS One hundred seventy-eight persons had zero ( group 1 ) and 141 ( 114 group 2 and 27 group 3 ) had non-zero anti-HBs levels at baseline . Response to the challenge dose was significantly higher among those with non-zero vs zero anti-HBs levels , irrespective of challenge dosage ; only 1 person with a non-zero anti-HBs level failed to respond to the challenge dose ( group 3 , 27/27 [ 100 % ] vs group 2 , 113/114 [ 99 % ] vs group 1 , 145/178 [ 82 % ] ; P<.0001 ) . CONCLUSIONS Among participants with residual anti-HBs levels less than 10 mIU/mL 16 - 19 years after primary hepatitis B vaccination during infancy , non-zero anti-HBs levels , with rare exception , indicated persistence of immune memory to HBsAg . TRIAL REGISTRATION Clinical Trials.gov Identifier : Response to hepatitis A and B vaccines has been reported to decline with age . This open , prospect i ve , single-site study examined the long-term response to the combined hepatitis A/B vaccine Twinrix  in 98 primary responders aged 45 - 67 years . Levels of antibody against hepatitis A virus ( HAV ) and hepatitis B surface antigen ( HBs ) were tested 30 months after initial vaccination . At this stage , all participants remained seropositive for anti-HAV and 70 % for anti-HBs . A booster vaccination was offered to those who had responded to the first vaccination but then lost protective levels of anti-HBs . An anamnestic response was observed in all cases Hepatitis A and B vaccines are highly immunogenic in three-dose schedules . To obtain an equivalent result in children with two paediatric doses would be of significant benefit . The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses , one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8 - 10 years were recruited in an open label study to receive either Twinrix Pediatric ( 360 El . U HAV antigen ; 10 microg HBsAg ) or Recombivax ( 2.5 microg HBsAg ) vaccine intramuscularly 6 months apart . The seroconversion ( > /=1 mIU/ml for anti-HBs antibodies and > /=33 mIU/ml for anti-HAV antibodies ) , seroprotection ( anti-HBs > /=10 mIU/ml ) rates and the geometric mean titers ( GMTs ) were determined 4 - 8 weeks after the second dose . The anti-HBs seroconversion rate was 97.1 % with Twinrix and 97.2 % with Recombivax . The seroprotection rates were 96.5 and 94.4 % , respectively ( P = 0.17 ) . The GMT was higher with Twinrix than with Recombivax ( 3248 mIU/ml versus 742 mIU/ml , P < 0.0001 ) . All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml . The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8 - 10-year-old children . This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs OBJECTIVE To evaluate the immunogenicity and reactogenicity of two lots of a combined hepatitis A-hepatitis B vaccine ( HAV , HBV ) in healthy 15 to 18 year olds . DESIGN This was a double-blind , r and omized clinical study . Vaccine was administered into the deltoid at 0 , 1 , and 6 months . Immunogenicity was assessed by anti-HAV and anti-HBs antibody levels at 2 , 6 , and 7 months after the first vaccine dose . Reactogenicity was assessed through use of 3-day diary cards following each vaccination , plus recording other unsolicited reactions . RESULTS A total of 160 adolescents were vaccinated ; 155 who were seronegative for hepatitis A and B at baseline and who completed the study were included in the immunogenicity analysis . The vaccine was well tolerated ; most side effects were local , of low intensity and short duration . Good immunogenicity was determined by antibody titers . High rates of seropositivity ( 99.4 % ) were achieved after two doses against HAV , and after three doses for anti-HBs ( seroprotection = 98.7 % ) . CONCLUSIONS This combination vaccine will be useful for immunizing selected high-risk groups in developed countries . In countries where endemicity is low for both diseases , targeting students prior to risk of acquisition would be a feasible preventive strategy PURPOSE This r and omized , open , controlled , multicenter study ( 110886/NCT00578227 ) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine ( HPV-16/18 vaccine ) coadministered with inactivated hepatitis A and B ( HAB ) vaccine . Co primary objectives were to demonstrate noninferiority of hepatitis A , hepatitis B , and HPV-16/18 immune responses at month 7 when vaccines were coadministered , compared with the same vaccines administered alone . METHODS Healthy girls ( 9 - 15 years ) were age-stratified ( 9 , 10 - 12 , and 13 - 15 years ) and r and omized to receive HPV ( n = 270 ) , HAB ( n = 271 ) , or HPV + HAB ( n = 272 ) . Vaccines were administered at months 0 , 1 , and 6 . Immunogenicity was evaluated at months 0 and 7 . RESULTS The hepatitis A immune response was noninferior for HPV + HAB , versus HAB , for seroconversion rates ( 100 % in each group ) and geometric mean antibody titers ( GMTs ) ( 95 % CI ) ( 4,504.2 [ 3,993.0 - 5,080.8 ] and 5,288.4 [ 4,713.3 - 5,933.7 ] mIU/mL , respectively ) . The hepatitis B immune response was noninferior for HPV + HAB , versus HAB , for anti-HBs seroprotection rates ( 98.3 % and 100 % ) ; GMTs were 3,136.5 [ 2,436.0 - 4,038.4 ] and 5,646.5 [ 4,481.3 - 7,114.6 ] mIU/mL , respectively . The HPV-16/18 immune response was noninferior for HPV + HAB , versus HPV , for seroconversion rates ( 99.6 % and 100 % for both antigens ) and GMTs ( 22,993.5 [ 20,093.4 - 26,312.0 ] and 26,981.9 [ 23,909.5 - 30,449.1 ] EL.U/mL for HPV-16 ; 8,671.2 [ 7,651.7 - 9,826.6 ] and 11,182.7 [ 9,924.8 - 12,600.1 ] EL.U/mL for HPV-18 , respectively ) . No subject withdrew because of adverse events . No vaccine-related serious adverse events were reported . Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population . CONCLUSIONS Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9 - 15 years . The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls In 1996 , a combined vaccine against both hepatitis A and B was licensed and commercialized and has been recommended for healthcare personnel in Belgium . This study compares the immunogenicity against hepatitis B virus ( HBV ) and safety of two vaccination schedules ( 0 - 1 - 12 months and 0 - 1 - 6 months ) with this vaccine . This is a r and omized , stratified and controlled study in healthy adult workers , who are not occupationally exposed to HBV .  Seroconversion ( ≥1 IU/L ) and seroprotection ( ≥10 IU/L ) rates were compared using Fisher 's exact test ; geometric mean concentrations ( GMCs ) of anti-HBs were compared using one-way ANOVA . All statistical analyses were carried out with SPSS 11 on Apple Macintosh . A total of 399 subjects were enrolled in the study , and 356 were analysed according to the protocol . The rate of ≥10 IU/L at 6 months was 70.6 % in the group 0 - 1 - 12 and 79.9 % in the group 0 - 1 - 6 ; this rate decreased to 55.9 % at 12 months in the first group . Seroconversion and seroprotective rates against HBV measured at month 13 in group 0 - 1 - 12 ( 98.9 % and 95.6 % ) and measured at month 7 in group 0 - 1 - 6 ( 99.4 % and 97.1 % ) were not statistically significantly different . GMC of anti-HBs after the 0 - 1 - 12 schedule was more than two fold higher than after 0 - 1 - 6 schedule ( P < 0.001 ) . Reported side effects were comparable in both groups with a slight tendency to fewer side effects in the 0 - 1 - 12 group after the third dose . The results from our study show that the completed schedule 0 - 1 - 12 offers at least equal protective immunogenicity against HBV as the completed 0 - 1 - 6 schedule . People not receiving their third dose at 6 months can be given this dose up to 12 months after the first dose . The drawback of this flexibility , however , is the longer time period before the protection becomes effective BACKGROUND Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS This r and omised , multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine ( Twinrix , Smithkline Beecham Biologicals ) compared with simultaneous administration of the two corresponding monovalent vaccines . The combined vaccine was administered on days 0 , 7 and 21 , whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0 , 7 and 21 . All subjects received booster vaccination at month 12 . RESULTS At month 1 , 100 % of subjects in the combined group and 99 % of the controls were seropositive for anti-HAV antibodies . The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9 % , respectively . Examination of the 95 % confidence intervals ( CIs ) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course . Just prior to the booster , the seropositivity rate for anti-HAV was 96.2 % in the combined group and 95 % in the control group . For anti-HBs , this was 94 and 91.6 % , respectively . All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13 . The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects . The anti-HBs titre was 26002 and 29,196mIU/ml , respectively . Both groups had a similar reactogenicity profile . CONCLUSIONS The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation In the past , immunogenicity of hepatitis A and B vaccines needed to be question ed in persons of advanced age , especially in those of 40 years and older . We performed a comparative multicenter prospect i ve and retrospective study with the combined hepatitis A and B vaccine Twinrix ® to identify factors influencing the results of the vaccination in a population of all age groups . Out of 489 subjects enrolled , 241 were vaccinated in a prospect i ve study ( group 1 ) and 248 subjects in a retrospective study ( group 2 ) in 17 German centers with median age of 40.1 ( 14 - 79 ) years . Following three applications of the combined hepatitis A/B vaccine we found 96.2 % with protective antibodies against HAV and 88.7 % were protected against HBV . With increasing age the subjects developed decreasing anti-HBs antibody levels whereas the seroprotection rate was significantly reduced by age ( A prospect i ve observational naturalistic study was conducted to assess the reactogenicity of the combined hepatitis A and hepatitis B ( HAB ) vaccine in a real-life setting . All healthy c and i date s for HAB vaccination attending an adult vaccination centre between October 1998 and February 2000 were invited to participate in the study . A follow-up diary card was provided to subjects to record local and general symptoms during a 4-day follow-up . Intensity was grade d from 1 to 3 . Redness was recorded as presence or absence . Fever was defined as axillar temperature > or = 37.5 degrees C and grade 3 > 39.0 degrees C. For all other symptoms , grade 3 was defined as an adverse reaction preventing normal everyday activities ; 998 subjects ( 74 % females ) , mean age ( + /-S.D. ) of 23 years ( + /-4.5 ) ( range : 11 - 54 years ) agreed to participate . At first immunization 92 % were < 30 years old .  Grade 3 pain and swelling was recorded in 1.2 % and 0.3 % of local symptom sheets completed , respectively ; 438 subjects received the HAB vaccine alone ( group 1 ) whereas 560 received at least one concomitant vaccine ( group 2 ) . In 45 % , 27 % , 18 % and 10 % of subjects the HAB vaccine was coadministered with 1 , 2 , 3 or 4 to 6 vaccines ( mainly Td adult-type , typhoid , MMR and IPV vaccine ) .  Grade 3 pain and swelling were recorded in 1.2 % & 0.3 % of symptom sheets ( SS ) , respectively . In group 1 , any fever and grade 3 fever was recorded in 3.5 % and 0.1 % of SS . Group 1 versus 2 had a lower risk for any fatigue ( p=0.0002 ; OR=0.617 ) and any malaise ( p=0.0076 ; OR=0.693 ) but not for grade 3 symptoms . In conclusion , our study showed that the HAB vaccine is well tolerated in adults either alone or coadministered with other vaccines in the routine clinical practice As with hepatitis B vaccines , the recently developed hepatitis A vaccine is suitable not only for individual protection , but also for public health control measures . For introduction into routine immunisation programmes , however , hepatitis A vaccine should preferably be combined with other already established vaccines . In particular , a combination of hepatitis A and hepatitis B vaccines would be appropriate . We investigated a new combined hepatitis A/hepatitis B vaccine comparing its tolerability and immunogenicity with that obtained after separate or mixed simultaneous administration of the two components . Three groups of healthy volunteers , each of approximately 50 persons , were included . All were negative for hepatitis A and hepatitis B markers and had normal liver enzyme values . They received hepatitis A ( 720 ELISA units ) and hepatitis B ( 20 micrograms ) vaccines in the deltoid muscle , combined , mixed or separately , according to a 0 , 1 , 6-month schedule . Blood sample s for determination of antibodies to hepatitis A virus ( anti-HAV ) and hepatitis B virus ( anti-HBs ) and of serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels were drawn at months 0 , 1 , 2 , 6 , and 7 . Local and systemic reactions were monitored by means of question naires . The results of our study demonstrate that the combined hepatitis A and B vaccine is well tolerated and highly immunogenic . The seropositivity and seroprotection rates were 100 % for both antigens in all groups . Surprisingly , anti-HAV and anti-HBs antibody titres after the combined and mixed vaccines were significantly higher compared with the respective monovalent vaccines injected separately Two studies were undertaken to investigate the concomitant administration of combined hepatitis A/B vaccine with a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with Haemophilus influenzae vaccine ( DTPa-IPV/Hib ) , or with a measles-mumps-rubella vaccine ( MMR ) , during the second year of life . On completion of the vaccination course , all subjects were seropositive or seroprotected against all antigens except for one subject who was seronegative for anti-PT . Seropositivity and seroprotection rates for all other antibodies were comparable to reference values for each vaccine component , indicating that the immunogenicity of MMR , DTPa-IPV/Hib and combined hepatitis A/B vaccines is not impaired by co-administration . All vaccines were well tolerated The vaccination  success and side effects of hepatitis A and hepatitis B immunisation of health care employees when using a combined vaccine were compared to those observed with simultaneous or single immunisations . The immunological response of two groups of healthy participants ( 75 each ) receiving either single HAV or HBV vaccination  was compared with that of two groups ( 75 each ) vaccinated either simultaneously with both vaccines or with the combined vaccine . There were no non or low responders with respect to hepatitis A vaccination . Only one participant failed to build up an anti-HBs titer after combined vaccination . The good tolerance of separate , simultaneous and combined vaccinations was confirmed . Both combined and simultaneous vaccination led to significantly higher anti-HAV titers than single immunisation , while markedly but not significantly higher anti-HBs titers were found only with simultaneous vaccination . Considering the additional advantage of the higher acceptance of only one injection with the combined vaccine , this vaccination should be recommended for employees at risk for both hepatitis A and hepatitis BACKGROUND Combined hepatitis A and B vaccine administered on an accelerated schedule provides a rapid immune response against both hepatitis A and B viruses , which might be especially relevant for individuals who need protection quickly . METHODS A prospect i ve , open-label , r and omized study to compare the immunogenicity and reactogenicity of the combined hepatitis A and B vaccine Twinrix ( GlaxoSmithKline Biologicals , Rixensart , Belgium ) ( > or=720 EL.U/mL inactivated hepatitis A antigen and 20 microg/mL recombinant hepatitis B surface antigen [ HBsAg ] ) administered at 0 , 7 , 21 to 30 days , and 12 months compared with concurrent administration of Havrix [ GlaxoSmithKline Biologicals , Rixensart , Belgium ( > or=1440 EL.U/mL inactivated hepatitis A antigen ) ] at 0 and 12 months , and Engerix-B [ GlaxoSmithKline Biologicals , Rixensart , Belgium ( 20 microg/mL recombinant HBsAg ) ] at 0 , 1 , 2 , and 12 months in seronegative healthy adults . RESULTS At month 13 , the anti-hepatitis B seroprotection rates ( > 10 mIU/mL ) for the combined vaccine compared to the monovalent hepatitis B vaccine were 96.4 % ( 95 % CI : 92.7 - 98.5 ) and 93.4 % ( 95 % CI : 89.0 - 96.4 ) , respectively . The anti-hepatitis A seroconversion rates were 100 % in both groups ( 95 % CI : 98.1 - 100 ) . At day 37 , the anti-hepatitis A seroconversion rates were similar in both groups ( 98.5 % for combined vaccine , 98.6 % for the monovalent vaccine group ) , but the combined vaccine result ed in a statistically significantly ( p < 0.001 ) better anti-hepatitis B seroprotection compared to monovalent hepatitis B vaccine , 63.2 % versus 43.5 % , respectively . The reactogenicity profile was similar in both study groups . CONCLUSIONS The combined hepatitis A and B vaccine administered on an accelerated schedule was at least as immunogenic and as well tolerated as the corresponding monovalent vaccines Combining several vaccines in a single formulation can change the potency of the vaccine antigens . Previous studies suggested a higher immunogenicity of a new combined hepatitis A and B vaccine compared with the monovalent hepatitis B vaccine . We investigated the immune response to hepatitis B surface antigen 1 month after the third vaccine dose in 282 healthy adults who had received either a monovalent hepatitis B vaccine ( n=148 ) or the combined hepatitis A/B vaccine ( n=134 ) . A slight trend towards higher geometric mean titres of anti HBs was found at this point in time in the group immunised with the combined vaccine , especially in the few vaccinees with preexisting antibodies against hepatitis A virus . However none of these differences was statistically significant , arguing against an advantage of the combined vaccine regarding hepatitis B immunisation RATIONALE A combined hepatitis A and B vaccine , Twinrix , containing at least 720 enzyme-linked immunosorbent assay units of hepatitis A antigen and 20 microg of hepatitis B antigen in the adult formulation and half those doses in the pediatric formulation , has been available in many countries since 1997 . This vaccine is administered on a three dose schedule : 0 , 1 and 6 months . A reduction in the number of doses would add convenience for the vaccinees and reduce administration-associated costs . We investigated the safety and immunogenicity profile of the adult formulation administered at 0 and 6 months in children ages 1 to 11 years . METHODS A total of 237 children of both sexes were enrolled . Blood sampling was performed at 0 and 1 , 2 , 6 and 7 months . Seropositivity for anti-hepatitis A virus was defined as > or = 33 mIU/ml and seroprotection against hepatitis B virus as > or = 10 mIU/ml . Data on solicited and unsolicited adverse events were collected on diary cards . RESULTS The vaccine was well-tolerated in all subjects . At Month 7 all subjects had seroconverted for anti-hepatitis A virus antibodies with a high geometric mean concentration ( 11 543 mIU/ml ) . We observed a continuous increase in anti-hepatitis B surface antibody ( anti-HBs ) seroconversion rates and seroprotection rates until Month 6 . After the second dose ( Month 7 ) , all subjects seroconverted for anti-HBs antibodies with a high geometric mean concentration ( 8056 mIU/ml ) and 98.5 % of the subjects were considered seroprotected . CONCLUSION The two dose adult formulation could be an alternative to prevent hepatitis A and hepatitis B infection in children ages 1 to 11 years 300 adolescents aged 12 - 15 years were r and omised ( 1:1 ) into two groups to compare the long-term ( 10 years ) immunogenicity profile of two doses of an Adult formulation [ Group HAB_2D : 150 ; 0 - 6 months ] vs. three doses of a Paediatric formulation [ Group HAB_3D : 150 ; 0 - 1 - 6 months ] of a combined hepatitis A and B ( HAB ) vaccine . At Year 10 , anti-HAV seropositivity rate was 100 % in both groups , while 85.9 % and 85.1 % subjects in the HAB_2D and HAB_3D groups , respectively , had anti-HBs antibody concentrations > or = 10 mIU/mL. The anti-HAV antibody GMCs ( HAB_2D : 429.3 mIU/mL ; HAB_3D : 335.5 mIU/mL ) and anti-HBs antibody GMCs ( HAB_2D : 50.6 mIU/mL ; HAB_3D : 60.1 mIU/mL ) were similar in both groups . No vaccine-related serious adverse events were reported . Hence , with respect to long-term antibody persistence , the two-dose schedule of the combined HAB vaccine Adult formulation is an effective alternative to the conventional three-dose schedule of the Paediatric formulation in adolescents It is important to monitor the long-term persistence of antibodies induced by vaccination . Four cohorts were followed for their long-term immunity after vaccination with a combined hepatitis A and B vaccine ( Twinrix ; SmithKline Beecham Biologicals , Rixsenart , Belgium ) . Two cohorts of adults ( ages 17 - 60 years ) , one of 1 - 6-year-olds , and one of 6 - 15-year-olds were vaccinated following a 0 , 1 , and 6-month schedule . Follow-up data until month 72 ( adults ) and month 60 ( children ) are available . At month 72 , antibody to hepatitis A virus ( anti-HAV ) seropositivity ( S+ ) was 100 % for both adult cohorts ( n = 40 and n = 47 ) and 95 % and 89 % of the vaccinees were seroprotected against hepatitis B virus ( HBV ) , respectively . The geometric mean titres ( GMTs ; mIU/ml ) for anti-HAV were 977 and 542 and the GMTs for the antibody to hepatitis B surface antigen ( anti-HBs ) were 322 and 90 . For 1 - 6-year-olds at month 60 ( n = 39 ) , anti-HAV S+ was 100 % with a GMT of 479 and 97 % were protected against HBV with a GMT of 195 . At month 60 for the 6 - 15-year-olds ( n = 42 ) , anti-HAV S+ was 100 % with a GMT of 990 and 95 % were protected against HBV with a GMT of 263 . There have been no safety issues during the follow-up . In the past 5 years , a postmarketing surveillance system was available . Using this system , all spontaneous adverse events are collected and archived . Although infrequent , the most commonly reported adverse events after more than 13 million doses were allergic-type reactions followed by fever and injection site reactions . The combined hepatitis A and B vaccine is safe and is well tolerated . Immunity provided by the vaccine remains high in adults and children with comparable results to those obtained with monovalent vaccines In an open , r and omized , multicenter , controlled clinical trial in the US , 773 adults were administered either a combination hepatitis vaccine ( Twinrix : 720 EL.U inactivated hepatitis A antigen and 20 mcg recombinant hepatitis B surface antigen per milliliter ) on a 0 , 1 , 6 month schedule or corresponding monovalent vaccines concurrently ( Havrix , 1440 EL.U/ml of hepatitis A antigen at 0 , 6 months and Engerix-B , 20 mcg of hepatitis B surface antigen at 0 , 1 , 6 months ) . Non-inferiority testing for the primary endpoint , severe soreness , and equivalence testing for the secondary endpoints , anti-HAV seroconversion and anti-HBs seroprotection , showed that safety and immunogenicity were comparable in the two groups OBJECTIVES Hepatitis A ( HAV ) and B ( HBV ) vaccinations are recommended in patients with chronic liver diseases . METHODS We prospect ively investigated immunogenicity and safety of an accelerated vaccination protocol ( 0 - 7 - 21 days ) with the combined hepatitis A/B vaccine ( Twinrix(R ) ) versus the st and ard vaccination scheme ( 0 - 1 - 6 months ) in hepatitis C virus-infected patients versus healthy volunteers . RESULTS Local and general symptoms were mostly mild in all groups . One month after completion of the accelerated vaccination or st and ard vaccination , with the combined hepatitis A/B vaccine anti-HAV seroconversion rates ( > 33 IU/l ) were 89 % and 88 % in HCV-infected patients . Initial HCV-nonresponders developed protective anti-HAV antibodies in 94 % and 96 % after a booster dose . According to the anti-HBs seroprotection rate , HCV-infected patients developed protective anti-HBs titres ( > 10 IU/l ) in 77 % and 82 % of cases one month after the accelerated and the st and ard vaccination scheme-at month 2 and 7 , respectively . This anti-HBs seroprotection rate could even be increased to 84 % and 85 % when initial HCV-infected nonresponders where given a booster dose with the combined hepatitis A/B vaccine . Protective anti-HAV and anti-HBs titers were achieved as early as month 2 after the accelerated vaccination schedule in the majority of HCV-infected patients . Healthy subjects developed protective anti-HAV titers and anti-HBs titers in 100 % and 98 % after the accelerated and st and ard vaccination protocol . CONCLUSIONS This study is the first to have demonstrated that the accelerated combined hepatitis A/B vaccination is both safe and highly immunogenic against HAV and HBV in HCV-infected patients with well compensated liver disease This open , r and omized study was conducted in healthy Chinese youngsters , aged between 10 and 19 years to compare the reactogenicity and immunogenicity of two vaccines : the combined vaccine against hepatitis A and B was administered in a two-dose schedule with the profile of the corresponding monovalent vaccines , while the concomitant vaccine was administered also on a two-dose schedule but simultaneously in opposite arms . All vaccinees had antibodies against hepatitis A ( anti-HAV ) after the 2-dose administration , whereas all but four in the first and two in the second group had protective titres against hepatitis B ( anti-HBs ) . At month 7 , the geometric mean titres for both antibodies were more than double for the group of subjects receiving the combined vaccine : 3,701 vs. 1,705 mIU/ml for the anti-HAV , and 1,524 vs. 720 mIU/ ml for the anti-HBs response . Injection site pain was the most commonly reported local symptom and headache was the most reported general symptom . It is concluded that this combined vaccine against hepatitis A and B , administered according to a two-dose schedule , is well-tolerated and highly immunogenic OBJECTIVES The primary objective of the study was to evaluate the immunogenicity of a combined hepatitis A and hepatitis B vaccine compared to the effect of the administration of two monovalent hepatitis A and B vaccines by quantitative measurements of the anti-HBs antibody levels at month 2 of the vaccination course . Secondary objectives were to assess immunogenicity of the vaccines investigated at other time points in the vaccination course ( months 1 , 6 and 7 ) , including the comparison of quantitative measurements results as well as to evaluate seroconversion and seroprotection rates . MATERIAL S AND METHODS The study was design ed as open , controlled , r and omized , monocentric study with two parallel groups . A total of 304 subjects , aged 18 - 45 years , were enrolled in the study . Group 1 received a combined hepatitis A and hepatitis B vaccine , group 2 was vaccinated concomitantly with a monovalent hepatitis A and hepatitis B vaccine .  Seroprotection against hepatitis B was defined as anti-HBs antibody concentration > or = 10 IU/l , and longterm seroprotection as > or = 100 IU/l . RESULTS In all , 288 subjects completed the study . One month after the second vaccine dose , the percentage of subjects with anti-HBs antibody concentrations > or = 100 IU/l as well as the seroconversion rate were significantly higher in group 1 than in group 2 . Similarly , anti-HBs GMC was higher after combined vaccination one month after the third vaccine dose ( 1.684 IU/l vs. 528 IU/l ; p < 0,0001 ) . After the vaccination course , all individuals were anti-HAV positive . The overall incidence of symptoms ( solicited/unsolicited , local/general ) tended to be similar in each of the two groups . CONCLUSIONS If health care personnel are exposed to hepatitis A and B virus , the combined vaccination should be preferred to the concomitant one , as this vaccination scheme induced earlier seroprotection against hepatitis B virus infection ( > or = 10 IU/l and > or = 100 IU/l ) The aim of this study was to assess the immunogenicity and reactogenicity of a combined vaccine against hepatitis A virus ( HAV ) and hepatitis B virus ( HBV ) in young healthy adults . A total of 150 subjects ( 20 + /- 1.4 years ; 111 females and 39 males ) negative for anti-HAV , anti-HBs , anti-HBc and HBsAg markers , were enrolled and r and omized to received the study vaccine from one of the three lots under double blind conditions . Three doses of the combined vaccine were administered by intramuscular route ( deltoid ) following a 0- , 1- and 6 months schedule . Each dose of 1 ml contained at least 720 ELISA Units of HAV antigen ( Strain HM175 ) and 20 micrograms of recombinant HBsAg .  Blood sample s for anti-HAV ( ELISA ) , anti-HBs ( RIA ) and transaminases determinations were obtained 1 month after the administration of each dose and before to the administration of the third dose ( month 6 ) . Local and general reactions were recorded by the vaccinee on the day of each vaccination and for the three following days on symptom sheets . A total of 147 subjects completed the study . There were not statistically significant differences between groups regarding to immunogenicity . All subjects had seroconverted [ geometric mean titres ( GMT ) : 1311 mIU ml-1 ] for hepatitis A component following the second dose ; GMT increased to 8895 mIU ml-1 after the third dose . Seroconversion rates for hepatitis B component were 98 % ( GMT , 104 mIU ml-1 ) after the second dose and 100 % after the third dose ( GMT , 7097 mIU ml-1 ) . There were not statistically significant differences between groups regarding to incidence of local and general symptoms . Soreness at the injection site and headache were the most commonly local and general symptoms reported , following 42 % and 11 % of the doses , respectively . This vaccine when given to young adults was well tolerated and induced high immunogenic response , similar to that obtained by hepatitis A and hepatitis B vaccines administered separately in previously reported trials OBJECTIVE A phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses . METHODS Both groups ( 1 - 16 years of age ) received combined ( inactivated ) HAV and ( rDNA ) HBV vaccine Ambirix ( ® ) at months 0 and 6 . Serum sample s were taken at four time points and tested for anti-HAV and anti-HBs antibodies . Anti-HAV concentrations ≥20 mIU/mL or anti-HBs concentrations ≥10 mIU/mL were considered protective . Seropositivity percentages were calculated and geometric mean concentrations ( GMCs ) were compared by nonparametric Mann-Whitney U-test or Kruskal-Wallis one-way- analysis -of-variance . RESULTS Of 80 HIV-infected children who completed the study , 67 were HAV-susceptible and 68 HBV-susceptible at enrolment . Of 80 children with rheumatic diseases who completed the study , 65 were HAV-susceptible and 74 HBV-susceptible at enrolment  . Immune responses to HAV after first dose of vaccine in both study groups were low : 71 % and 55 % respectively , whereas immune responses after the second dose were 99 % and 100 % respectively . Immune response to HBV after first dose of vaccine in both groups was also low : 27 % and 17 % respectively . Immune responses after the second dose were 97 % and 93 % , respectively . A larger proportion of children on combination antiretroviral therapy ( cART ) and of children with viral load < 50 copies/mL responded to HBV , and also showed a significantly higher GMC . CONCLUSIONS Although immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children , a substantial proportion of both groups was not protected for HAV after first dose of vaccine . This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment : both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine
BACKGROUND Hepatitis A and B are two of the most common vaccine-preventable diseases and vaccination for Hepatitis A virus ( HAV ) and hepatitis B virus ( HBV ) is recommended for those at risk of contracting HAV and /or HBV through their occupation , travel or lifestyle .