Anti-pre-S2 antibody response in subjects vaccinated against hepatitis B and in naturally immunized subjects

Serum samples from individuals immunized with a pepsinized or non-pepsinized vaccine and from patients who had recovered from acute hepatitis B or who developed a chronic form of the disease, were analysed for the presence of antibody against the pre-S2 epitope of the hepatitis B virus.Anti-pre-S2 antibody was absent in all but one individual immunized with the pepsinized vaccine. Thirty-eight percent of the subjects who responded by anti-HBs production to the non-pepsinized preparation showed anti-pre-S2 antibody one year after complete vaccination. Among subjects who did not produce anti-HBs after immunization with this vaccine, 1 single individual produced anti-pre-S2 antibody. Anti-preS2 antibody was detectable after one year in 38% of the patients who recovered from acute hepatitis B, but in none of those with chronic hepatitis B. The kinetics of anti-pre-S2 antibody response to a booster injection was also analysed 1 month and 1 year after the 3rd injection and 1 month after the 4th injection of the non-pepsinized vaccine.     

The positive rates of hepatitis B surface antibody in youth after booster vaccination: a 4-year follow-up study with large sample

Background: Hepatitis B virus (HBV) infection is still a public issue in the world. Hepatitis B vaccination is widely used as an effective measure to prevent HBV infection. This large-sample study aimed to evaluate the positive rates of hepatitis B surface antibody (anti-HBs) in youth after booster vaccination.Methods: A total of 37788 participants were divided into two groups according to the baseline levels of anti-HBs before booster vaccination: the negative group (anti-HBs(−)) and the positive group (anti-HBs(+)). Participants were tested for anti-HBs levels after receiving a booster vaccine at 1 and 4 years.Results: The positive rates of anti-HBs were 34.50%, 73.80% and 67.32% before booster vaccination at 1 and 4 years after vaccination, respectively. At 4 years after the booster vaccination, the positive rates of 13–18 years were 47.54%, which was the lowest level among all youth age groups. In the anti-HBs(−) group, the positive conversion rates of anti-HBs were 74.62% at 1 year after receiving a booster vaccine, and 67.66% at 4 years after vaccination. In the anti-HBs(+) group, the positive maintenance rates of anti-HBs were 70.16% after 1 year, and 66.66% after 4 years. Compared with the baseline anti-HBs (+) group, the positive rates of the baseline anti-HBs(−) group were higher at 1 and 4 years after receiving the booster vaccine.Conclusion: The positive rates of anti-HBs declined over time, especially the positive maintenance rates were the lowest at age of 13–18 years.     

Immunogenicity of Hepatitis B Virus Vaccine (Heptavax-B)—Response of Healthy Adults

We vaccinated 30 healthy adults who were susceptible to hepatitis B virus with 20 μg of Merck Sharp & Dohme vaccine at zero, one and six months and measured their antibody (anti-HBs) response weekly for four weeks and monthly for at least seven months. A month following the first dose 40% had antibodies and 90% were positive for anti-HBs a month following the second dose. The third dose raised the response rate to 93.3% but its major effect was to substantially raise the titer of virtually all of the vaccinees. Two persons had no antibody response to vaccination and four others were hyporesponders. No complications or significant side effects were observed.     

Response to Booster Doses of Hepatitis B Vaccine among Young Adults Who Had Received Neonatal Vaccination

Background

Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question.

Aims

The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future.

Methods

A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults.

Findings

Among 212 students, 17–23-year-old, born after adoption of neonatal immunization, 2 (0.9%) were HBsAg positive, 40 (18.9%) were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs <10 mIU/mL, 29.0% and 56.5% were 10–100 and >100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047). At 2–4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10–100 mIU/mL.

Conclusions

Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.     

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.     

不同剂量乙肝疫苗阻断乙型肝炎病毒母婴传播的远期效果观察

本文对出生后接种不同剂量乙肝血源疫苗的２７２名婴儿进行了３－５年的效果随访观察。结果表明,接种３、４、５年后,抗－ＨＢｓ阳性率仍分别保持在９０．５％、８２．３％和７３．２％,ＨＢｓＡｇ阳性率分别为２．８％、３．１％和４．２％。３年后抗－ＨＢｓ阳性率逐年下降,Ｐ／Ｎ值＞５０者以接种后３年为多,＜５０者以５年为多,３年后也呈下降趋势。随访结果说明,接种１０μｇ×４、５μｇ×４及２．５μｇ×４剂量的乙肝疫苗具有阻断母婴乙肝病毒传播的效果。鉴于Ｐ／Ｎ值及抗－ＨＢｓ阳性率在接种后３年开始下降,建议接种后３年应进行一次加强接种。     

Immunogenicity of a DNA-recombinant hepatitis B vaccine (Engerix B) given at 3, 5 and 11 months of age with a new schedule suitable for mass vaccination programmes

Following the demonstration of a fully satisfactory immunogenic activity of a hepatitis B vaccination protocol consisting of three doses given at the 3rd and 5th months of age with a booster at 11, it was possible to administer this vaccine at the same times as the vaccinations for diphtheria, tetanus and polio which are mandatory in Italy at those ages. A field trial of this protocol in a hyperendemic area near Naples (prevalence of HBsAg about 14%) started on January 1987. The French vaccine, Hevac B, Pasteur, was used. At this time compliance is 99%, and fully satisfactory results both in terms of seroconversion rate (96.3%) and of mean anti-HBs titre (4,352 mIU/ml) two months after the booster dose have been obtained. In this paper we demonstrate that even for a new hepatitis B vaccine prepared by a DNA-recombinant technique (Engerix B, SK & F) recently introduced in Italy, the same schedule can be used. In fact two doses of this vaccine, the first given at three months of age and the second two months later, resulted in a 100% seroconversion rate and a mean anti-HBs titre of 560 mIU/ml. Two months after the booster given at 11 months of age the mean anti-HBs titre was 12,100.     

HBsAg阴性母亲及其婴儿乙肝疫苗接种情况和免疫效果研究

目的：了解乙肝表面抗原阴性（HBsAg阴性）母亲及其婴儿乙肝疫苗接种情况及抗-HBs滴度水平,从而为今后针对该特殊人群进行更好的乙肝疫苗免疫策略提供依据。方法：2010年5月～2010年10月,对陕西省227对HBsAg阴性母亲及其婴幼儿（月龄为8～24月）进行流行病学调查并采集血液标本,对母婴血清抗-HBs进行定性及定量检测。结果：母亲乙肝表面抗体（抗-HBs）阳性率为45.4%,抗-HBs平均滴度为12.88 mIU/mL（95%CI：8.91-18.19）。婴儿乙肝疫苗首针、第二针和第三针的及时接种率分别为95.2%,93.8%和85.9%。婴儿抗-HBs阳性率为77.1%,抗-HBs平均滴度为37.15 mIU/mL（95%CI：28.18-48.98）。结论：婴儿乙肝疫苗首针及时接种率较高,但三针全程及时接种率仍需提高。母亲抗-HBs阳性率较低,应当重视HBsAg阴性孕龄妇女的乙肝疫苗接种及乙肝标志物的检测,从而提高该人群的乙肝免疫水平。     

The vaccinal prophylaxis of hepatitis B in Russia--the achievements, problems and outlook

Certain specific features of the present epidemic situation with hepatitis B (HB) in Russia were established: significant growth of HB morbidity, starting from 1995; the prevalence of persons aged 15-29 years among HB patients, which was linked with the sharp activation of the sexual route of the transmission of HB virus in recent years; an essential increase in the number of patients having contacted this virus in the process of the intravenous use of drugs. The results of the use of vaccine "Engerix B" among persons belonging to different risk groups were considered (a decrease in HB morbidity among them by 8-19 times was noted), the study demonstrated high immunogenicity anti-HBs antibodies on protective titers were determined in 92.3-95.7% of the vaccinees) and low reactogenicity of the vaccine, as well as stable postvaccinal immunity (5 years after the course of vaccination was completed anti-HBs antibodies were retained in 70.6-74% of the vaccinees). The study showed that only the vaccination of adolescents in combination, in the presence of opportunity, with the immunization of newborn infants and young children in the first year of their life made it possible to produce an essential effect on the activity of the epidemic process. Already in 2 years such organization of work on the prophylaxis of HB in one of the cities of the Sverdlovsk region led to a decrease in HB morbidity by 2.9 times, and among adolescents 9 times.     

国产甲型肝炎灭活疫苗用于儿童免疫效果研究

为了探讨国产甲型肝炎灭活疫苗在儿童中应用的免疫效果,选择2～15岁抗-HAV阴性健康易感儿童91名作为接种对象,采用0、6程序接种国产甲型肝炎灭活疫苗250U／剂,观察免疫后的局部反应和全身反应,并于全程免疫后一个月检测抗-HAV阳转率和抗体GMT。结果91例观察对象在初免和加强免疫后均未见即时副反应,只在8～72小时内出现轻微的一过性局部和全身反应。全程免疫后一个月抗-HAV阳转率为100％。抗体GMT为14 407mIU／ml。国产甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性,采用0、6个月程序可获得高滴度抗体。     

Comparative study of the antigenic activity and allergic transformation of the body in human revaccination with different doses of a chemical brucellosis vaccine

The study of different doses of chemical brucellosis vaccine (0.5 mg, 0.75 mg and 1 mg), used for the booster immunization of persons who had received primary immunization with chemical and live brucellosis vaccines, revealed that the characteristics of its antigenic potency were somewhat higher after primary immunization with the live vaccine. When used for booster immunization, the tested doses showed no differences in their antigenic potency irrespective of prior immunizations received by the immunized persons. In booster immunization chemical brucellosis vaccine was found to have poorly pronounced allergenic properties irrespective of its booster dose with the tendency towards greater sensitization to brucellosis allergen in persons primarily immunized with the live vaccine. When considering the possibility of using brucellosis chemical vaccine in medical practice, the complex evaluation of the characteristics showing its reactogenicity and antigenic potency, as well as the allergic transformation of the body induced by the injection of the vaccine, was carried out, which made it possible to recommend 1 mg of the vaccine as the optimal booster dose.     

Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus: Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L) protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.     

Immunisation of neonates at high risk of hepatitis B in England and Wales: national surveillance.

The results of a voluntary programme of immunisation against hepatitis B in neonates at high risk (mother being positive for hepatitis B surface antigen and without hepatitis B e antibody or having had acute hepatitis B late in pregnancy) are reported. The programme was offered in England and Wales from November 1982. Passive immunisation alone was available in the first six months of life until 1985, after which infants received passive and active immunisation from birth; in addition, some infants received passive immunisation for six months followed by a course of hepatitis B vaccine. All but a few infants received the first immunising dose within 48 hours after birth. Blood samples for analysing markers of hepatitis B virus were available at 1 year from 147 of the 223 infants given passive immunisation, 54 of the 72 given passive followed by active immunisation, and 102 of the 155 given passive and active immunisation at birth. At 1 year 11 of the 127 (9%) infants given four or more doses of specific hepatitis B immunoglobulin were positive for hepatitis B surface antigen compared with four of the 20 given three or fewer doses; 11 had levels of hepatitis B surface antibody greater than 50 IU/l. Only one of the 54 infants given passive then active immunisation was positive for hepatitis B surface antigen at 1 year and four infants had low (less than or equal to 50 IU/l) levels of hepatitis B surface antibody. Four of the 102 infants who received passive and active immunisation at birth were positive for hepatitis B surface antigen. Two had received the fill course of vaccine, whereas in the other two vaccination was incomplete or unstated. In 79 of the 89 infants who received a complete course of vaccination the level of hepatitis B surface antibody was known, and 70 had levels at 1 year greater than 100 IU/1. Reactions to immunisation were not severe at any age. The incidence of side effects was 8% for the immunoglobulin, 11% for the vaccine, and 9% when immunoglobulin and vaccine were given together. Wider collaboration in the programme is requested.     

The reactogenicity and immunogenicity of the Urabe Am 9 live mumps vaccine and persistence of vaccine induced antibodies in healthy young children

The immunogenicity and reactogenicity of the Urabe Am 9 mumps virus vaccine strain were studied after the administration of different doses of the vaccine to 197 children ranging in age from seven and a half months to nine years and without a history of mumps. There was no effect of dose on the response in serum neutralizing antibodies in the range of 10(2.9) to 10(4.7) TCID50/dose. In the 90 subjects without detectable serum neutralization antibodies before vaccination seroconversion was obtained in 94.4% after 42 days. Half of a group of 34 seropositive children who were tested also showed a fourfold or greater rise in antibodies. Persistence of vaccine-enhanced haemagluttinin-inhibition (EHI) antibodies was satisfactory as only two of 46 vaccinees followed-up for between 27 and 32 months had undetectable levels of EHI antibodies and the geometric mean titre of vaccine-induced EHI antibodies had only fallen to about one-third by 32 months after vaccination. Although there was serological evidence of a subclinical re-infection in three subjects, to date none of the vaccinees has had clinical mumps indicating that the vaccine confers protection against disease. The vaccine was well tolerated. Furthermore, the majority of the few 'reactions' reported were probably not vaccine-related. It is concluded that the Urabe Am 9 is an acceptable strain for use in live mumps vaccines.     

Presence of maternal anti-HBs antibodies does not influence hepatitis B vaccine response in Brazilian neonates

Recently, it was suggested that maternal hepatitis B surface antigen antibodies (anti-HBs) acquired transplacentally could play a negative role in newborn infants' immune response to the hepatitis B vaccine. We compared the hepatitis B virus (HBV) vaccine response in infants born to mothers previously vaccinated against HBV (n = 91) to infants born to mothers who were not previously vaccinated (n = 221). All newborn infants received three intramuscular doses (10 μg) of HBV vaccine (Butang?) at 0,1 and six months. The first dose was administered at the maternity hospital within 12 h of birth. The geometric mean titres of anti-HBs were not different among newborn infants born to mothers who were anti-HBs-negative (492.7 mIU/mL) and anti-HBs-positive (578.7 mIU/mL) (p = 0.38). Eight infants did not respond to the HBV vaccine. Of them, six were born to anti-HBs-negative mothers and two were born to mothers with anti-HBs titres less than 50 mlU/mL. Despite the mother's anti-HBs-positive status, our data show a good immunogenicity of the Brazilian HBV recombinant vaccine in neonates.     

Immunogenicity of hepatitis B surface antigen derived from the baculovirus expression vector system: a mouse potency study

A standard mouse potency test was performed to evaluate the immunogenicity of recombinant hepatitis B surface antigen (HBsAg) produced in the baculovirus/insect cell expression system. Groups of NIH Swiss mice were immunized with serial four-fold amounts of either baculovirus-derived HBsAg adsorbed to aluminum sulfate or a commercially available yeast-derived recombinant HBsAg vaccine preparation. Results from these experiments showed that the effective dose of baculovirus- and yeast-derived HBsAg vaccine preparations necessary to seroconvert 50% of the animals were similar. The duration of the antibody response to HBsAg was studied in mice immunized with the highest doses of the two recombinant vaccine preparations 3 and 6 months after injection. No decrease in the anti-HBs response was observed 6 months after injection. No decrease in the anti-HBs response was observed 6 months after immunization with either of the two vaccine preparations. These results indicate that the baculovirus-derived recombinant HBsAg could serve as an alternative vaccine candidate for hepatitis B virus.     

钦南区1～6岁儿童乙肝及白喉疫苗免疫效果分析

目的分析钦南区儿童乙肝及白喉疫苗接种后的免疫效果,为该地区儿童免疫规划工作提供科学依据。方法采用整群随机抽样方法,选取5个乡镇1~6岁常住儿童151名为调查对象,进行病毒性乙型肝炎(乙肝)、白喉血清学检测,并对结果进行分析。结果 HBsAg阳性2人,阳性率1.32%;抗-HBs阳性112人,阳性率74.17%。白喉IgG阳性142人,阳性率94.04%。抗-HBs中位数21.32 mIU/mL,白喉IgG中位数0.14 mIU/mL,乙肝疫苗首针及时接种率83.44%;男女抗-HBs阳性率、白喉IgG阳性率、抗体中位数差异均无统计学意义(P0.05),抗-HBs阳性率、白喉IgG阳性率随年龄的增长而下降(P0.01)。结论钦南区1~6岁儿童乙肝疫苗接种率、首针及时接种率均达到了国家免疫规划的目标,白喉IgG阳性率维持较高的水平,但HBsAg阳性率略高于国家免疫规划的目标,儿童免疫规划工作仍需进一步加强。     

Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard. RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. CONCLUSION: A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.     

Epidemiological effectiveness of an inactivated three-component flu vaccine with an increased concentration of hemagglutinin in the inoculation dose]

The work presents the results of the evaluation of mass immunization of working adults with inactivated trivalent influenza vaccine under the conditions of an epidemic caused by influenza viruses A (H1N1), A (H3N2) and B. This immunization produced no effect on influenza morbidity in the groups of vaccinees in comparison with those of nonvaccinated persons. The index of effectiveness was 1.0 and less. The ineffectiveness of mass immunization was due to a high level of natural immunity to influenza and the extensive use of influenza vaccine in past years.     

不同来源血浆对静注人免疫球蛋白中抗-HBs、白喉抗体效价的影响

调查分析不同来源原料血浆对静注免疫球蛋白(IVIG)制品内的抗-HBs、白喉抗体效价的影响。选择6个单采血浆站,对其提供的血浆为原料制备的IVIG所含的抗-HBs抗体、白喉抗体效价进行了测定。检测结果显示,用A、B、C、D、E、F编号的6个相应血浆站采集的血浆为原料制备成IVIG其抗-HBs抗体(IU/g)效价分别为33.77、103.95、70.94、132.45、78.84、58.28;白喉抗体平均效价分别为5.17、7.36、4.26、7.67、10.14、9.24。6个单采血浆站间的IVIG制品中白喉抗体效价无明显差异,但抗-HBs效价却存有显著差异。