Immunogenicity of the intradermal route of hepatitis B vaccination with the use of recombinant hepatitis B vaccine

In March 1987, 32 hospital employees were enrolled in a prospective trial of intradermal recombinant hepatitis B vaccination. Enrollees were given 0.1 ml of vaccine on days 1, 30, and 180. Two weeks after the third intradermal vaccination, 81%, or 26, of the enrollees showed seropositivity (greater than or equal to 10 mIU antibody/ml) for hepatitis B surface antibody. Five of six nonresponders were given a fourth intradermal vaccination. Two additional seroconversions occurred, resulting in an overall conversion rate of 90% for recipients of up to four intradermal vaccine doses. Complications of vaccination were limited primarily to the occasional persistence (less than 6 months) of hyperpigmentation at the injection site. Administration of recombinant hepatitis B vaccine by the intradermal route proved to be a safe and effective method of vaccination. Cost savings of preexposure immunization with the intradermal versus the intramuscular route of vaccination were approximately $90 per enrollee. Efficacy and safety can be maximized by employing a fourth vaccine dose and routinely documenting seroconversion after vaccination.     

Afebrile convulsion in an adult after recombinant hepatitis B vaccination

Vaccination against HBV is important in order to reduce the incidence of HBV infection. Although the HBV vaccine is among the safest of all vaccines, vaccination against HBV has been associated with side-effects. Herein we present a case of afebrile convulsion after recombinant HBV vaccination.     

Immunogenicity of recombinant hepatitis B vaccine: comparison of two different vaccination schedules

Background  

Neonatal immunization with hepatitis B (HB) vaccine induces protective levels of antibody (anti-HBs ≥10 IU/L) in a majority of vaccines. However, the duration of protection after HB vaccination in infants is unknown. A smaller proportion of children vaccinated beginning at birth with three doses of HB vaccine were found to have protective titers 5–10 years after initial vaccination. Long-term efficacy of HB vaccine depends mainly on peak antibody levels after vaccination, and subjects were observed to have lower levels of antibodies if they received the first dose of vaccine immediately after birth. The aim of our study was to compare the immunogenicity of two different HB vaccine schedules in infants born to HB surface antigen-negative mothers.     

Immuneresponse to recombinant hepatitis B vaccination in adults

The present study was conducted to find out the seroconversion following Recombinant Hepatitis B vaccination in healthy adults. Eighty healthy adults (males and females) of age group 18 yrs to 60 yrs were chosen for the study. Their prevaccination blood samples tested negative for HBsAg and Anti HBs antibodies by ELISA test. The subjects were administered 3 doses of recombinant Hepatitis B-(Engerix B) vaccine at 0, 1 and 6 months duration using 20 micrograms of vaccine per dose. Seropositivity (anti HBs titre > or = 10 mIU) after 2 doses was 48.75% and was 91.25% after 3 doses of the vaccine. 8.75% of the vaccinees did not seroconvert. The non responders when further scrutinized did not show evidence of HIV or Hepatitis C infection and they had a normal haemogram and normal immunoglobulins (IgA,IgM,IgG) levels. However 2 such subjects were found to be positive for anti HBc IgG antibodies indicating chances of Hepatitis B infection from a mutant strain of HBV where it is not possible to detect presence of HBs Ag using currently available diagnostic kits.     

HIV感染者乙型肝炎疫苗不同接种方案效果比较

目的 探讨HIV感染者短程接种高剂量乙肝疫苗的免疫效果、依从性和安全性.方法 以广西两所疾病预防控制中心管理的182名HIV感染者为对象,随机分组后接受0-1-6月20 μg(IM20*3组)或0-1月60 μg(IM60*2组)乙肝疫苗接种,随访检测两组第二针接种后5个月与IM20*3组接种后6个月的抗-HBs,分析...     

Immunogenicity of a recombinant hepatitis B vaccine in hemophiliacs

Yeast-recombinant vaccines against hepatitis B virus (HBV) are now available, but there is no information about whether or not they are immunogenic in patients with hemophilia and other congenital bleeding disorders. Twenty micrograms of a recombinant vaccine expressing the adw serotype of the hepatitis B surface antigen (HBsAg) were given to 41 patients negative for HBV markers and again after 1 and 6 months. Ten percent of the vaccinees had anti-hepatitis B surface antibody (anti-HBs) responses, with titers of 10 mIU/ml or more, 1 month after the first dose of vaccine. The percentage of anti-HBs-positive patients increased to 54% after the second dose and to 98% after the third dose, with only one non-responder. Hence, the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers similar to those achieved with plasma-derived vaccines.     

Immunogenicity of recombinant hepatitis B vaccine in dialysis patients

Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen.     

Immunogenicity of peptide fusions to hepatitis B virus core antigen.

Several gene fusions have been constructed in which coding sequences for antigenic regions of the pre-S sequences of hepatitis B virus, hepatitis B surface antigen, and the envelope protein of human immunodeficiency virus were linked to the 3' end of that for the first 144 residues of hepatitis B core antigen. The sequences were expressed efficiently in Escherichia coli to give stable products that assembled to form particles morphologically similar to hepatitis B core antigen itself. The products exhibited the antigenic and immunogenic characteristics of both the hepatitis B core antigen epitopes and the epitopes carried by the additional sequences, thus illustrating the value of such proteins as immunological reagents and potential vaccines.     

Production of antibody to hepatitis A virus and hepatitis B surface antigen measured after combined hepatitis A/ hepatitis B vaccination in 242 adult volunteers

Two batches of a new hepatitis A/hepatitis B combined vaccine were tested in 242 healthy students. Three injections, given at 0, 1 and 6 months, produced seroconversion rates and hepatitis A virus (HAV) and hepatitis B surface antigen (HBsAg) antibody levels comparable to those reported after administration of separate monocomponent vaccines. The vaccine proved to be safe and well-tolerated. Influence of host factors, such as elevated body mass index or gender, were investigated and proven to be of little influence on the immunoresponse.     

乙肝表面抗原载体多价重组核酸疫苗研究进展

研究表明,乙肝病毒的包膜蛋白HBsAg不仅可以作为疫苗的理想候选分子,还可作为基因工程疫苗的理想载体,用来成功构建多种重组核酸疫苗。本文概述了以乙肝表面抗原为载体,重组或联合其他病毒、寄生虫、细胞因子等其他基因制作多价核酸疫苗的研究进展。     

新型乙型肝炎病毒核心区核酸疫苗的免疫原性研究

目的观察新型乙型肝炎病毒(HBV)核心抗原(HBcAg)核酸疫苗的免疫原性。方法应用新型人体应用载体质粒pSW389l构建HBcAg核酸疫苗(pSW3891／HBc)，对照组和实验组Balb／c小鼠分别以基因枪法免疫对照载体质粒(PSW3891)和HBcAg核酸疫苗，采用酶联免疫吸附试验检测抗HBc，乳酸脱氢酶(LDH)释放测定法检测小鼠HBcAg特异性cTL杀伤活性。结果HBcAg核酸疫苗可在体外293T细胞中高效表达，免疫小鼠后可产生高滴度抗HBc(1：97200)，免疫鼠脾细胞HBc特异性CTL杀伤活性达73．25％。结论新型HBcAg核酸疫苗在Balb／c小鼠实验中表现出良好的体液和细胞免疫原性。     

Immunogenicity of two accelerated hepatitis B vaccination protocols in liver transplant candidates

OBJECTIVE: It is common practice to immunize patients against hepatitis B virus infection prior to orthotopic liver transplantation (OLT). We compared the seroprotection rates of two accelerated schedules with a recombinant hepatitis B vaccine in patients awaiting OLT. DESIGN AND METHODS: Patients were prospectively recruited and vaccinated with either 20 micrograms (group 1, n = 14) or 40 micrograms (group 2, n = 20) hepatitis B surface antigen per dosage. Thirty-nine healthy volunteers served as a historical control group. Patients in all groups were vaccinated with an accelerated schedule (0, 7 and 21 days). All patients underwent clinical and laboratory examinations (HBs antibodies, CD4/CD8 ratio, transaminases). RESULTS: The accelerated hepatitis B vaccination schedules were well tolerated. Eight weeks after the third injection, no significant differences in seroprotection rates were observed between group 1 (31%) and group 2 (26%). There was no correlation with respect to seroconversion rates and gender, smoking habits or CD4/CD8 ratio. CONCLUSION: These data suggest that accelerated vaccination schedules with a recombinant hepatitis B vaccine are safe and well-tolerated, but only achieve poor seroconversion rates in OLT candidates. Increasing the vaccine dose to 40 micrograms hepatitis B surface antigen per injection did not result in a higher response rate. Because of the low risk of acquiring de novo hepatitis B infection after transplantation, it should be questioned whether routine hepatitis B vaccination with standard recombinant vaccines prior to liver transplantation should be recommended any longer.     

维持性血液透析病人多次皮内小剂量接种基因重组乙型肝炎疫苗的疗效观察

目的 探讨血液透析（HD）病人多次皮内小剂量接种基因重组乙型肝炎疫苗的免疫效果。方法 研究对象包括慢性HI）病人15例常规（0，1，6）接种基因重组乙肝疫苗20μg（A组），慢性HD病人15例多次（6～8次，间隔时间2周）小剂量（5μg）皮内注射接种基因重组乙肝疫苗（B组）。以抗体滴度〉10IU／ml为产生保护性抗体，达到100IU／ml停止接种。在疫苗接种期间，每月检测一次抗体滴度。结束后在1，3，6月检测抗体滴度。结果 A组病人有10例产生了抗体，阳转率为65％，在第6个月检测时只有8例病人抗体滴度在10IU／ml以上，为53％。B组病人全部产生了抗体，且在第6个月检测时滴度都在10IU／ml以上，为100％。结论 HD病人多次皮内小剂量接种基因重组乙型肝炎疫苗可有效地产生保护性抗体，并且持续6个月以上。     

人乙型肝炎免疫球蛋白定量清除新生儿乙型肝炎病毒表面抗原的研究

目的 根据新生儿出生时HBsAg和HBV DNA的载量,调整人乙型肝炎免疫球蛋白使用量,以期更有效地阻断HBV的母婴传播. 方法 收集出生2h内静脉血HBsAg阳性新生儿资料125例.分为研究组64例,对照组61例,研究组根据新生儿出生时HBsAg感染量调整乙型肝炎免疫球蛋白使用量,与对照组比较新生儿12个月龄以上治疗效果.计量资料采用非正态分布采用秩和检验,计数资料采用x2检验.结果 2组新生儿出生时HBsAg和HBV DNA检测值的差异均无统计学意义(p 值均＞0.05).研究组出生HBV感染新生几64例,12月龄以上成功清除HBsAg者53例,成功清除率为82.8％,感染11例(1.2％).对照组出生HBV感染新生儿61例,12月龄以上成功清除HBsAg者35例,成功清除率为57.4％,感染26例(3.1％).2组出生HBV感染新生儿12个月龄以上清除HBsAg效果比较,x2=9.696,P＜0.05,差异有统计学意义.结论 根据新生儿的HBsAg感染量调整使用乙型肝炎免疫球蛋白,可提高乙型肝炎母婴传播的阻断成功率.     

Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs

Of 1,801 Chinese subjects, age 1 to 90 years, screened for hepatitis B surface antigen and antibody (HBsAg, anti-HBs) and antibody to hepatitis B core antigen (anti-HBc), 214 (11.9%) had an isolated, positive anti-HBc result; anti-HBc was reproducibly present in the initial sera in only 66% and persisted after an interval of 2 weeks to 3 months in only 73%. There was a strong correlation between the rates of reproducibility and persistence of isolated anti-HBc and the initial anti-HBc titers. Thirty-two subjects with persistent, isolated anti-HBc received four doses of hepatitis B vaccine (5 micrograms, HEVAC B) at 0, 1, 2 and 12 months: 56% developed a primary anti-HBs response in response to hepatitis B vaccine, 16% developed an anamnestic or secondary anti-HBs response, and 28% were undetectable for anti-HBs even after four doses of vaccine. The low rates of reproducibility and persistence of anti-HBc together with the high rate of primary anti-HBs response to hepatitis B vaccine in subjects with isolated anti-HBc raise doubts as to the reliability of anti-HBc (Corzyme, Abbott Laboratories, North Chicago, Ill.) as a single screening test for hepatitis B infection prior to vaccination and suggests that subjects with isolated anti-HBc, in particular those with low anti-HBc titers, be included in vaccination programs.     

Long-term response to hepatitis B vaccination and response to booster in children born to mothers with hepatitis B e antigen

Hepatitis B (HB) vaccine provides an uncertain duration of protection and the optimal timing of booster vaccine remains unclear. This study examined the immune response at 10 years of 118 children who had developed protective anti-HB surface (anti-HBs) levels after a primary series of HB immunizations in infancy. All of the children were born to hepatitis B e Antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers. HB markers in all subjects and cellular immune response in some were determined. A booster was given to all subjects after the collection of samples and another blood sample was collected 4 weeks later. The results showed that a total of 39 (33%) of the children were seronegative for anti-HBs. T-cell proliferative response to HBsAg was noted in 47% of children. On HBsAg stimulation, leukocyte samples from a significantly higher proportion of subjects produced cytokines (81% of T cells produced interleukin-2 [IL-2] and 100% produced IL-5). The booster dose of HB vaccine induced the production of a protective level of anti-HBs (>/=10 mIU/mL) in all subjects. Cellular immunity was augmented with a positive rate of 58%, 90%, and 100% for HBsAg-induced T-cell proliferation, IL-2 production, and IL-5 production, respectively. Although 14 (11.9%) of the subjects were HB core antibody positive at 10 years of age, no new HBsAg carrier was detected. The results of this study show that protection afforded by HB vaccination persisted to the age of 10 years in all vaccinees. Immunologic memory was detected in all subjects including those who had lost their anti-HBs seropositivity. These results suggest that no booster vaccination is needed before 10 years of age. The most sensitive marker of immunologic memory is IL-5 production of T cells. (HEPATOLOGY 1999;29:954-959.)     

Comparison of three different recombinant hepatitis B vaccines： GeneVac-B, Engerix B and Shanvac B in high risk infants born to HBsAg positive mothers in India

AIM: To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to hepatitis B surface antigen (HBsAg) positive mothers. METHODS: A total of 158 infants were enrolled in the study. Fifty eight infants were enrolled in the GeneVac-B group while 50 each were included for Engerix B and Shanvac B groups. A three-dose regimen of vaccination; at birth (within 24 h of birth), 1st mo and 6 mo. were adopted with 10 μg dosage administered uniformly in all the three groups. Clinical and immunological parameters were assessed for safety and immunogenicity of the vaccines, in all the enrolled infants. RESULTS: Successful follow up until seven months of age was achieved in 83/ (48/58) for GeneVac-B, 76/ (38/50) and 64/ (32/50) for Engerix B and Shanvac B groups respectively. 100/ seroconversion and seroprotection was achieved in all the three groups of infants. The geometric mean titers of anti-HBs one month after the completion of three dose of vaccination were 90.5, 80.9 and 72.5 mIU/mL in GeneVac-B, Engerix B and Shanvac B vaccine group respectively. Furthermore the level of anti-HBs increases with age ofbabies who were born to HBsAg positive mothers. The GMT values of anti-HBs were 226.7, 193.9 and 173.6 mIU/mL respectively in GeneVac-B, Engerix B and Shanvac B groups one year after the completion of the three doses of vaccine. No systemic reactions were reported in infants during the entire vaccination process of GeneVac-B and the other two vaccines. Clinical safety parameters remained within the normal limits throughout the study period.CONCLUSION: The study concludes that there is no significant difference between the three recombinant hepatitis B vaccines. Administration of these vaccines within 24 h of birth to babies, born to HBsAg positive mothers will reduce the incidence of HBV infection.