倍尔来福TM甲、乙型肝炎联合疫苗安全性和免疫原性研究

目的 观察倍尔来福~(TM)甲、乙型肝炎(甲、乙肝)联合疫苗的安全性和免疫原性。方法以高中一年级(成人组)和小学1～5年级(儿童组)学生为研究对象,按对甲、乙肝病毒均易感、只对甲肝病毒易感和只对乙肝病毒易感分为AB组、A组和B组,按0、1和6个月三剂程序分别接种甲、乙肝联合疫苗、灭活甲肝疫苗和重组乙肝疫苗。疫苗剂量成人组每剂含甲肝病毒抗原500U和(或)HBsAg10μg,儿童组减半。疫苗接种后72h内观察副反应,免疫后2、7个月采集血清标本检测抗-HAV和抗-HBs。结果 儿童AB组和成人AB组局部副反应发生率分别为0.58％(2/344)和2.56％(8/312),全身副反应发生率分别为9.88％(34/344)和5.45％(17/212),与对照组相比差异无显著性。局部反应主要是轻度疼痛,全身反应主要是低热。免疫后7个月,两组抗-HAV阳转率均为100％,与A组相同;抗体滴度(GMT)分别为33 910mIU/ml和23 435 mIU/ml,显著高于A组;两组抗-HBs阳转率分别为97.30％和96.63％;GMT为103 mIU/ml和102 mIU/ml,抗-HBs阳转率及GMT均与B组差异无显著性。结论 倍尔来福~(TM)甲、乙肝联合疫苗与单价甲肝灭活疫苗和单价重组乙肝疫苗具有相同的安全性和免疫原性。     

Antibody persistence six years after two doses of combined hepatitis A and B vaccine

Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12–15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2–6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6, received an additional HBV vaccine dose ∼12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations ≥10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations ≥100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.     

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, 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.     

Safety and immunogenicity of a combined vaccine against hepatitis A and B in patients with autoimmune hepatitis

Patients with autoimmune hepatitis (AIH) are a group at risk of disease exacerbation or relapse of the underlying disease should they fall ill with infectious hepatitis A (HAV) or B (HBV). Therefore, it seems appropriate to protect this group of persons against HAV and HBV disease by vaccination. An open study evaluated the safety, reactogenicity and immunogenicity of a combined HAV and HBV vaccine in 10 patients with AIH (6 patients aged 1-15 years and four patients aged 16+ years). The vaccine was administered using a three-dose vaccination schedule (0, 1 and 6 months). The vaccine course was well tolerated, safe and did not aggravate the clinical course of the underlying disease. Patients responded with 100% seroconversion for antibody to the HAV vaccine component and geometric mean antibody concentration (GIVIC) comparable to healthy cohorts. Response to the HBV component antigen was comparable to previous reports of HBV vaccination in immune compromised individuals with lower GMC than observed in healthy populations. One month after the third vaccine dose (month 7), all six vaccinees in the 1-15 years age group developed protective levels of anti-HBs as compared to two of the four vaccinees in the 16+ years age group.     

Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study

An open, randomised 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 μg 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)10 mIU/ml) and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies (i.e., 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.     

Comparison of the reactogenicity and immunogenicity of a two injection combined high-dose hepatitis A and hepatitis B vaccine to those of Twinrix

Twinrix (SmithKline Beecham Biologicals) is a combined hepatitis A and B vaccine licensed with a three-dose schedule. A two-dose combined hepatitis A and B vaccine would facilitate immunisation programs. In this prospective study, 100 healthy adults, aged between 18 and 40, were enrolled. A first group of 50 was given a high-dose vaccine at month 0 and 6. A second group of 50 received Twinrix at month 0, 1 and 6.The reactogenicity was assessed after each vaccine dose. There were no severe local adverse events. Seven severe systemic reactions occurred, of which five were fatigue, one was headache and one consist in gastrointestinal symptoms. They all resolved during the 4-day follow-up period. One serious general adverse event was reported, but was clearly unrelated to the vaccine. Thus, both vaccines were well tolerated.The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. At month 7, the anti-HAV GMTs were higher in the high-dose group than in the Twinrix group and, inversely, the anti-HBs GMTs were slightly higher in the Twinrix group than in the high-dose group. At month 7, all subjects in both groups were positive for anti-HAV. All subjects in the high-dose group and 97.6% subjects in the Twinrix group had seroconverted for anti-HBs. Therefore, it can be concluded that with two injections of the high-dose hepatitis A and B vaccine, 6 months apart, a similar immune response can be obtained as induced with three doses of Twinrix at months 0, 1 and 6.     

Hepatitis A/B vaccination of adults over 40 years old: comparison of three vaccine regimens and effect of influencing factors

Challenged by contrasting data on low immune responses in the elderly with a combined hepatitis A/B vaccine, a randomised, 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.     

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine

BackgroundThe exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence.MethodsSubjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12–15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11–15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15 mIU/mL; anti-HBs: <10 mIU/mL).Results209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10 mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience.ConclusionImmunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination.Trial registrationhttp://www.clinicaltrials.gov NCT00875485.     

Antibody persistence and immune memory elicited by combined hepatitis A and B vaccination in older adults

Response to hepatitis A and B vaccines has been reported to decline with age. This open, prospective, 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.     

A two-dose schedule for combined hepatitis A and B vaccination in children aged 6-15 years

A combined hepatitis A and B vaccine, Twinrix, in a paediatric formulation for ages 1-15 years and in an adult formulation for those ages 16 years and older, became commercially available in Turkey as well as in many countries. It is administered according to a three-dose schedule (0, 1 and 6 months). A reduction in the number of doses would improve the compliance rate and reduce administration costs. Therefore, we planned a trial evaluation of the immunogenicity, safety and reactogenicity profile of a high-dose combined hepatitis A and B vaccine, administered in two doses, compared with the profile of a paediatric-dose combined vaccine, administered in three doses, in healthy children aged 6-15 years. One hundred children were randomly attributed to the two study groups. The first group (paediatric-dose vaccine group) received the licensed Twinrix Paediatric, at months 0, 1 and 6; the second group (high-dose vaccine group) received the high-dose vaccine, following a 0, 6 months schedule. The reactogenicity was assessed after each vaccine dose. The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. Both formulations of the combined vaccine were well tolerated. The high-dose combined vaccine administered in two doses, elicits satisfactory immunogenicity profiles, similar to those elicited by the paediatric vaccine administered in three doses. On completion of the vaccination schedule in the two groups all children were protected against hepatitis B and immune for hepatitis A. Anti-HAV GMTs after completion of the vaccination schedule were 7163 mlU/ml in the paediatric-dose group, 8241 mlU/ml in the high-dose group; anti-HBs GMTs were 8679 and 4583 mlU/ml, respectively. These results indicate that a two-dose schedule, compared with the standard three-dose schedule, offers fewer injections for satisfactory protection against the two infections. This means fewer clinic visits, lower administration costs, better compliance, and higher coverage rate. Therefore, this two-dose schedule can be considered an appropriate regimen for the immunization of children and adolescents against hepatitis A and B infection, in the context of school-based immunization programmes.     

甲、乙型肝炎联合疫苗在儿童中0、6月程序接种的安全性和免疫原性研究

目的 观察和评价在儿童中接种2剂倍尔来福~(TM)甲、乙型肝炎(分别简称为甲肝、乙肝)联合疫苗的安全性及免疫原性.方法 本研究以江苏省常州市116名1～10岁完成乙肝疫苗全程免疫同时无甲肝疫苗接种史的抗甲肝病毒抗体(anti-hepatitis A virus,抗-HAV)阴性儿童为研究对象,按0、6个月程序接种甲、乙肝联合疫苗(倍尔来福~(TM)).每剂疫苗0.5 ml,含HAV抗原250 U和乙肝表面抗原5μg.观察接种疫苗后72 h内局部反应和全身反应,检测免疫后1、6、7个月的血清抗-HAV阳转率、乙肝病毒表面抗体(抗-HBs)保护率及抗体滴度.结果 倍尔来福~(TM)接种后局部和全身不良反应发生率分别为12.1%(14/116)和6.0%(7/116),其中局部不良反应以注射部位红、肿、硬结为主,占6.9%(8/116)～11.2%(13/116),全身不良反应发生率为6.0%(7/116),以发热为主.免疫后1、6、7个月,抗.HAV阳转率为92.9%(92/99)～100.0%(101/101),抗体几何平均滴度(GMT)为47.0～2762.3 mIU/ml;疫苗免疫前抗-HBs阳性保护率为86.1%(87/101),免疫后1个月达到100.0%(101/101),免疫后1、6、7个月抗-HBs GMT为894.3～3314.3 mlU/ml.结论 倍尔来福~(TM)甲、乙肝联合疫苗2剂接种程序在乙肝基础免疫儿童中应用具有良好的安全性和免疫原性.     

Hepatitis A and hepatitis B vaccinations: immunogenicity of combined vaccine and of simultaneously or separately applied single vaccines

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 B.     

Immunogenicity and reactogenicity of a combined high dose hepatitis A and hepatitis B vaccine, compared to that of Twinrix in healthy Indian children

BACKGROUND AND AIMS: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are vaccine preventable important childhood acquired infectious diseases in developing countries. In the changing epidemiology of HAV, the utility of such a vaccine in India needs urgent attention. Further, the efficacy of two versus three dose schedule needs to be assessed to improve compliance. SUBJECTS AND METHODS: One hundred healthy school children, aged 1-15 years were recruited in a randomised open study to receive either vaccination schedule: Group I: combined high-dose hepatitis A and B vaccine to be administered on a 0, 6 month schedule intramuscularly; Group II: to be administered on 0, 1, 6 month Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) schedule intramuscularly. The seroconversion (> or =1MIU/ml for anti-HBs antibodies and > or =33MIU/ml for anti-HAV antibodies) and seroprotection (anti-HBs > or =10MIU/ml after the third dose of vaccine) rates were determined at months 1, 2, and 7. RESULTS: The mean age and gender was similar between groups: 7.9+/-2.6 years (range 3-15 years). At month 7 all subjects (100%) in both groups were seropositive for anti-HAV antibodies, Group I had higher anti-HAV titres at months 1 or 2 compared to Group II (P=0.025, P=0.040). Group II developed higher seroprotection rates (month 2, P=0.002, month 6, P=0.003) compared to Group I and higher titres (month 2, P=0.001, month 6 P=0.001) compared to Group I. At month 7, the geometric mean titres (GMTs) were comparable between groups and seroprotection reached 100% in both the groups. The incidence of any symptom per dose analysis reported during a 4-day follow-up period was significantly higher in Group I, 53% (52/98) of the documented doses compared to 37% (54/146) in Group II (P=0.018). CONCLUSION: Twinrix vaccine is safe and highly immunogenic in Indian children. Further study of the high dose vaccine would determine if its two dose regimen is a feasible advantage.     

Evaluation of immune responses to combined hepatitis A and B vaccine in HIV-infected children and children on immunosuppressive medication

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 samples 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.     

新兵接种甲、乙型肝炎联合疫苗安全性和2年免疫效果评价

目的评价新兵接种甲、乙型肝炎联合疫苗安全性和2年免疫效果。方法300名符合条件新兵分为A组、B组和AB组,均按0、1、6个月免疫程序分别接种单价甲肝疫苗,单价乙肝疫苗和甲、乙型肝炎联合疫苗。观察首次免疫后7个月和24个月的免疫效果。结果AB组局部副反应发生率和全身副反应发生率分别为11.8%和9.1%,与对照组相比差异无显著性,局部副反应主要是接种部位的疼痛,全身副反应主要是低热。AB组和A组的抗-HAV阳性率在7个月和24个月时均为100%,AB组抗-HAV几何平均滴度(GMT)在7个月和24个月时均高于A组(P<0.05)。AB组抗-HBs阳性率和几何平均滴度(GMT)在7个月和24个月时均高于B组,但差异均无显著性(P>0.05)。结论新兵接种甲、乙型肝炎联合疫苗与单价甲肝疫苗和单价乙肝疫苗相比有相同的安全性,而且在首次免疫后7个月和24个月时点具有较高的免疫原性。     

Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children

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.     

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1-5 year and 6-11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).     

国产甲肝减毒活疫苗(IA-1株)与进口甲肝灭活疫苗的2年免疫效果比较

目的　比较国产甲肝减毒活疫苗和进口甲肝灭活疫苗免疫效果。方法　在广西柳城县筛选出 6～ 1 2岁甲肝易感儿童 2 1 7人 ,以个体随机分为 4个组。B、C组接种国产甲肝减毒活疫苗 (LA - 1株 ,滴度 1 0 6 75 TCID5 0 ) ,接种程序分别为 0 - 6和 0 - 1 2 ;D组接种低滴度国产甲肝减毒活疫苗 (LA - 1株 ,滴度 1 0 6 0 TCID5 0 ) ,E组接种史克公司市售甲肝灭活疫苗 (贺福立适 ,72 0E1 .U) ,接种程序均为 0 - 6。各组于第 1针免后 1 ,6 ,1 2 ,2 4个月 ,第 2针免后 1个月采血 ,用美国ABBOTT公司的ImxmEIA试剂 ,检测甲肝抗体IgG。 结果　滴度 1 0 6 75 TCID5 0 的国产减毒活疫苗两种程序 ,除 0 - 6程序组在第 2针免后 1个月的抗体水平峰值较低外 ,其余各次随访的抗体反应结果均与进口甲肝灭活疫苗相似。低滴度减毒活疫苗 ( 1 0 6 0 TCID5 0 )的抗体阳性率和抗体水平均低于其他各组。结论　滴度 1 0 6 75 TCID5 0 国产甲肝减毒疫苗与进口甲肝灭活疫苗免疫效果相近 ,具有良好的免疫原性和很好的回忆反应 ,加强免疫可以提高疫苗的保护效果和延长保护年限。     

Immunogenicity of a new, low-cost recombinant hepatitis B vaccine derived from Hansenula polymorpha in adults

BACKGROUND: Hepatitis B virus (HBV) infection is highly prevalent world over, especially in developing countries. A new recombinant hepatitis B virus (GeneVac-B; Serum Institute of India Ltd.) vaccine is developed using Hansenula polymorpha yeast. We decided to assess the immunogenicity, and reactogenicity of this vaccine in a large adult population. MATERIAL AND METHODS: Seven hundred eighty-eight adults subjects (age: 19-57 years, male:female ratio 35:1) received three 20 microg doses of a H. polymorpha-derived recombinant hepatitis B vaccine in months 0, 1, and 6. All the eligible subjects had negative baseline serum HBs Ag, and anti-HBs. The anti-HBs titer was obtained 1 month after the last dose of vaccine and was considered seroconverted if more than 1 mIU/ml, and seroprotective if more than 10 mIU/ml. RESULTS: The seroprotection rate was 96% and seroconversion rate was 97%. Seroconversion and seroprotection rates declined with increasing age. The minimum geometric mean titre of anti HBs was 443 mIU/ml (95% CI 407-482). Seroprotection was 96% in age group<40 years, while the same was 91% in >40 years group (Odd's ratio-2.9100, Z value-2.6183, highly significant). No other factor like smoking, tobacco-chewing, alcohol consumption, chronic diseases, and obesity, affected the immune response. No significant adverse reactions were reported in any of the subjects. CONCLUSIONS: Three standard doses of the H. polymorpha-derived recombinant HBV vaccine are highly immunogenic and safe in a predominantly male adult population. Young adults respond better with this vaccine. Because of its low cost, the vaccine may be a good choice in prevention of hepatitis B infection.     

Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1–11 years

This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1–11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies ≥15 mIU/mL, while 94–97% of subjects in both groups had anti-HBs antibody concentrations ≥10 mIU/mL. Subjects with anti-HBs antibody concentration ≤10 mIU/mL were administered a challenge dose of hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.