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。     

新生儿国产重组(酵母)乙型肝炎疫苗免疫效果考核

为了考核新生儿接种国产重组(酵母)乙型肝炎(乙肝)疫苗后的免疫效果,并与血源乙肝疫苗效果比较。对1997年出生并接种重组(酵母)乙肝疫苗的新生儿隔年随访一次,采血检测乙肝病毒表面抗原(HBsAg),乙肝病毒表面抗体(抗-HBs)和乙肝病毒核心抗体(抗-HBc),1998年以后对乙肝免疫人群开展急性乙肝发病监测。显示五年期间3次随访检测HBsAg阳性率平均为1.5%,较免前本底的HBsAg阳性率呈较大幅度下降,疫苗保护率为83%(95%可信区间为76.97%~89.02%),无论母亲HBsAg阳性或阴性,使用不同乙肝疫苗的儿童HBsAg阳性率没有统计学差异。接受重组(酵母)乙肝疫苗免疫的对象中,无一例急性乙肝病例报告。重组(酵母)乙肝疫苗有较好的近期保护效果和免疫原性,与以前使用血源乙肝疫苗效果相当。     

Success of a program of routine prenatal screening for hepatitis B surface antigen: the first 2 years.

Prenatal screening for hepatitis B surface antigen (HBsAg) restricted to women with defined risk factors for chronic hepatitis B virus (HBV) infection fails to identify many carriers. A centralized program of routine HBsAg screening for all pregnant women in Alberta was introduced in 1985. We collected and analysed data for the first 2 years of the program in Edmonton to determine the frequency of risk factors for HBsAg positivity, the proportion of multiparous HBsAg-positive women not identified in previous pregnancies, the efficiency and cost-effectiveness of providing immunoprophylaxis to infants at risk of HBV infection and the degree of success in inducing adequate protection. A total of 149 women (158 pregnancies) were found to be HBsAg positive. Risk factors were readily ascertainable for 85% of the women; the remaining 15% would not have been identified through risk-selective screening. The most common risk factors were Oriental ethnic origin, history of hepatitis, jaundice or multiple transfusions of blood or blood products, and occupational exposure to blood. Although 86% of the multiparous HBsAg-positive women had risk factors, only 7% had been identified in previous pregnancies. The Alberta program appears to be cost-effective. We conclude that only routine prenatal screening will identify all infants at risk of perinatal HBV infection and that a comprehensive public health program involving central laboratories, private physicians and public health staff can be highly effective and efficient in protecting infants against hepatitis B.     

Evaluation of the G145R Mutant of the Hepatitis B Virus as a Minor Strain in Mother-to-Child Transmission

The role of the hepatitis B virus (HBV) mutant G145R, with a single change in amino acid 145 of the surface protein, as a minor population remains unknown in mother-to-child transmission. The minor strain as well as the major strain of the G145R mutant were evaluated in three cohorts using a locked nucleic acid probe-based real-time PCR. The breakthrough cohort consisted of children who were born to HBV carrier mothers and became HBV carriers despite immnoprophylaxis (n = 25). The control cohort consisted of HBV carriers who had no history of receiving the hepatitis B vaccine, hepatitis B immunoglobulin or antiviral treatment (n = 126). The pregnant cohort comprised pregnant women with chronic HBV infection (n = 31). In the breakthrough cohort, 6 showed positive PCR results (major, 2; minor, 4). In the control cohort, 13 showed positive PCR results (major, 0; minor, 13). HBeAg-positive patients were prone to have the G145R mutant as a minor population. Deep sequencing was performed in a total of 32 children (PCR positive, n = 13; negative, n = 19). In the breakthrough cohort, the frequency of the G145R mutant ranged from 0.54% to 6.58%. In the control cohort, the frequency of the G145R mutant ranged from 0.42% to 4.1%. Of the 31 pregnant women, 4 showed positive PCR results (major, n = 0; minor, n = 4). All of the pregnant women were positive for HBeAg and showed a high viral load. Three babies born to 3 pregnant women with the G145R mutant were evaluated. After the completion of immunoprophylaxis, 2 infants became negative for HBsAg. The remaining infant became negative for HBsAg after the first dose of HB vaccine. G145R was detected in one-fourth of the children with immunoprophylaxis failure. However, the pre-existence of the G145R mutant as a minor population in pregnant women does not always cause breakthrough infection in infants.     

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.     

Passive-active immunisation of neonates of HBsAg positive carrier mothers: preliminary observations.

Screening of pregnant women for hepatitis B surface antigen (HBsAg) in three areas of Holland led to the identification of HBsAg carriers, 20 of whom were subsequently delivered. Within two hours after birth all infants received hepatitis B immune globulin (0.5 ml/kg body weight) and, after randomisation, hepatitis B vaccine (10 micrograms) was given either at 0, 1, and 2 months of age or at 3, 4, and 5 months of age, the latter concomitantly with DPTP vaccination. Eighteen infants complying with the protocol were followed up for at least six months. No side effects were observed after either passive or active immunisation. All infants developed high concentrations of anti-HBs antibodies; no interference of high dose passive immunisation with active immunisation was observed. Concentrations of anti-HBs at three months were significantly lower in infants given delayed active immunisation than in those given early active immunisation. These data suggest that passive-active immunisation against hepatitis B virus infection is well tolerated by neonates under 3 months of age and that both early and late active immunisation in combination with passive immunisation will result in excellent anti-HBs production.     

Transmission of HBsAg from mother to infant in four ethnic groups.

Antenatal screening in the West Midlands during a three-year period identified 297 mothers who were chronic carriers of hepatitis B surface antigen (HBsAg)--a prevalence of about 1 in 850. About half of their infants had HBsAg in the cord blood, but of 122 infants followed up for over three months (mean 8.5 months) only 17 (14%) were still positive for HBsAg. Cord-blood HBsAg-positivity was evenly distributed among different ethnic groups, but the transmission rate was highest among the Chinese, and no carriers were discovered among 39 European infants. Raised serum transaminase concentrations were found in some of the carrier infants who were otherwise healthy. The results suggest that adequate follow-up of HBsAg-positive infants may be achieved by tests at 4 months and 1 year of age, and that the role of breast-feeding in mother-to-infant transmission of HBsAg is unimportant. The Chinese community may be a suitable population in which to test the effectiveness of specific immunoglobulin administration at birth in preventing the development of the HBsAg carrier state.     

Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers

Background

Despite the use of hepatitis B (HB) vaccine and hepatitis B immunoglobulin (HBIG), a portion of infants are still non- or low-responders, or even immunoprophylaxis failure. We aimed to determine the immune response in the infants from the mothers being positive for hepatitis B surface antigen (HBsAg), by which the infants received three doses of HB vaccine in combination with two-dose 200 IU HBIG injections.

Methods

In this retrospective study, 621 infants from HBsAg-positive mothers in Beijing YouAn Hospital between January 2008 and December 2009 were included. All the infants were given three doses of 10 µg HB vaccine (at 0, 1 and 6 months of age) and two-dose of 200 IU HBIG (at birth and in 2 weeks of age). Serum HBsAg and antibody to HBsAg (anti-HBs) in all the infants were determined at 7 months of age.

Results

Of the 621 infants, 2.9% were immunoprophylaxis failure (positive for HBsAg), 1.4% were non-responders (anti-HBs undetectable), 95.7% were responders. The 594 responders could be categorized into three subsets, 22 were 10 to 99 IU/L for anti-HBs levels, 191 were 100 to 999 IU/L, and 381 were ≥1000 IU/L. The immunoprophylaxis failure rate was at 0% and 5.2% for the infants of HBeAg-negative and HBeAg-positive mothers(P<0.001). Infants from mothers with detectable HBV DNA had higher incidence of immunoprophylaxis failure than those of mothers without detectable HBV DNA (P = 0.002). The factors including gender, birth weight, gestation weeks, the rates of maternal HBeAg-positive, and detectable HBV DNA did not contribute to the no response to HB vaccination.

Conclusions

Through vaccination by three doses of HB and two-dose of HBIG, majority of the infants (95.7%) achieved a protective level of anti-HBs at 7 months of age. Maternal HBeAg-positive and HBV DNA detectable were associated with the immunoprophylaxis failure, but not contribute to the non- or low-response to HB vaccination.     

潍坊市坊子区2012年产前HBsAg筛检及新生儿首针乙肝疫苗接种情况分析

目的：了解住院分娩产妇乙肝病毒表面抗原（ HBsAg）检测及其所生新生儿首针乙肝疫苗及时接种情况,为进一步完善新生儿乙型肝炎的免疫预防策略提供依据。方法对2012年坊子区设有产科的医院每月上报的产妇HBsAg 检测和新生儿首针乙肝疫苗接种资料进行分析。结果坊子区2012年设有产科的医疗机构共报告住院分娩产妇2975名,产前HBsAg筛检2881名,筛检率为96．84％,各医疗机构筛检率在96．55％和97．50％之间;检出HBsAg阳性者66例,阳性率为2．29％,各医疗机构阳性率在0．00％和5．52％之间。新生儿共2975名,其中常住者所生新生儿2612名,流动者所生新生儿363名,常住和流动的新生儿乙肝疫苗接种率分别为96．13％和94．21％,及时接种率分别为93．87％和90．36％,差异均无统计学意义（χ2＝2．98、3．67,P＞0．05）。122名未及时接种首针乙肝疫苗的新生儿系患各种疾病所致。结论坊子区2012年设有产科的医院对住院的孕产妇产前HBsAg筛查率较高,其所生的新生儿24 h内乙肝疫苗及时接种率较高。     

Properties of recombinant hepatitis B vaccine

A large-scale purification method for hepatitis B surface antigen produced in a recombinant yeast (Saccharomyces cerevisiae) was established. The resulting HBsAg was greater than 99% pure and suitable for vaccine use. The yeast-derived HBsAg was structurally and biochemically similar to plasma-derived HBsAg. The anti-HBs antibody producing potency of the yeast-derived vaccine in mice was significantly higher than that of the plasma-derived vaccine. The yeast-derived vaccine induced protective antibody against hepatitis B virus of either adr or ayw subtype in a chimpanzee efficacy study. These observations demonstrate the usefulness of the yeast-derived vaccine as a second-generation hepatitis B vaccine.     

Correlation between Vertical Transmission of Hepatitis B Virus and the Expression of HBsAg in Ovarian Follicles and Placenta

Background

The aim of this study was to investigate the correlation between the expression of hepatitis B surface antigen (HBsAg) in human ovary and placenta and the vertical transmission of hepatitis B virus (HBV).

Methodology/Principal Fidnings

Ovarian and placental tissue specimens of pregnant women infected with HBV were collected during cesarean section and immunostained for HBsAg. The sera of the corresponding newborns were tested for HBV markers and HBV DNA. HBsAg was detected in 15 out of 33 (45%) placental tissues and was further detected in capillary endothelial cells in 4 specimens (26%), of which 3 (75%) corresponding infants were infected with HBV in utero. Out of the 33 ovarian tissues, 7 (21%) were positive for HBsAg, of which 2 (28%) showed HBsAg in ovarian follicles and the 2 corresponding infants (100%) had intrauterine HBV infection.

Conclusions/Significance

HBsAg expression in cells of the ovarian follicle or placental capillary endothelium signal a higher risk for intrauterine HBV infection.     

Adaptability of the anti-hepatitis-B vaccine Recombivax HB to the Piazza protocol for the mass vaccination of newborn infants]

27 healthy babies born to HBsAg, antiHBs and antiHBc negative mothers were given three doses of hepatitis B vaccine "Recombivax HB" (5 micrograms/dose/0.5 ml) at 3, 5 and 11 months of age (Piazza's protocol). AntiHBs response was highly satisfactory. Since both in terms of seroconversion rate and of mean antiHBs titre immunogenicity of other hepatitis B vaccines given at 3, 5 and 11 months of age was already demonstrated, it is possible to conclude that Piazza's protocol is valid for all hepatitis B vaccines available in Italy and will certainly facilitate the compulsory hepatitis B vaccination in infants in Italy.     

湖南省9所医院早产儿卡介苗及乙肝疫苗接种情况及未接种原因分析

目的:了解湖南省9所医院早产儿卡介苗及乙肝疫苗接种现状,并分析未接种的原因。方法:收集2014年11月至2015年10月期间参与研究的湖南省9所医院产科分娩的早产儿相关临床资料及卡介苗和第一剂乙肝疫苗的接种资料,分析各医院的接种原则以及未接种的原因。结果:各医院间早产儿的出生体重及出生胎龄比较差异均有统计学意义(P0.05);9所医院遵循的卡介苗和第一次乙肝疫苗接种原则不尽相同;出院时卡介苗未接种率为45.0%,明显高于第一剂乙肝疫苗未接种率的16.7%(P0.05);卡介苗因低体重、疾病、IVIG、家长拒绝而未接种的比例分别为82.5%、12.9%、4.3%、0.3%,第一剂乙肝疫苗因疾病、低体重、IVIG、家长拒绝而未接种的比例分别为53.1%、41.6%、4.0%、1.3%。结论:湖南省9所医院早产儿卡介苗及乙肝疫苗接种率较低,疾病和低体重位居出院时未接种原因的前两位,应规范早产儿疫苗接种,避免遗漏或不恰当推迟疫苗接种。     

Characteristics of the formation of the HBsAg carrier state among pregnant women and newborn infants and their role in the spread of hepatitis B

The authors analyze the incidence rate of HBsAg carriership among 8, 120 pregnant women and 261 newborn infants at different periods after birth. The levels of HBsAg carriership among pregnant women and the members of their families, as well as among the personnel of maternity clinics and blood donors, have been established. The rate and time of the detection of HBsAg in infants born to mothers found to be HBsAg carriers have been determined. Measures for the prophylaxis of hepatitis B are discussed with due regard to the specific epidemiological features of the spread of HBsAg carriership, established in this study, and to the presence of antibodies to HBsAg among the above-mentioned groups of the population.     

A modified immunisation schedule for the hepatitis B vaccine Recombivax HB suitable for mass vaccination in childhood.

Following the demonstration of a fully satisfactory immunogenic activity of a hepatitis B vaccination protocol consisting of three doses of Hevac B Pasteur vaccine given at 3,5 and 11 months of age, 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. We have also shown that both another plasma-derived vaccine, H-B-VAX (MSD), as well as the DNA-recombinant Engerix B (SK&F) are highly immunogenic when given at the same times as the mandatory childhood vaccinations. In this paper we demonstrate that the same schedule can be used for another hepatitis B vaccine prepared by a DNA-recombinant technique, Recombivax HB (MSD) recently introduced in Italy. 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 440 mUI/ml. Although the date are incomplete since the third dose will be given at 11 months of age, we conclude that this hepatitis B vaccine can also be used in the mass vaccination campaigns of infants in Italy, the first of which was initiated in January 1987 in an hyperendemic area near Naples (HBsAg prevalence about 14%). We underline that this mass vaccination campaign is the first in Europe.     

The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis

ABSTRACT: Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis, approximately 10-15% of newborns from HBV carrier mothers suffer from HBV infection through intrauterine transmission. One of the risk factors is the level of maternal viraemia. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV. A few studies have evaluated the efficacy of telbivudine in preventing intrauterine HBV infection during late pregnancy. So we conducted this meta-analysis to arrive at an evidence-based conclusion. We searched Medline/PubMed, EMBASE, Cochrane Library, Web of Knowledge and China Biological Medicine Database from January 1990 to December 2011. Relative risks (RR) of the seropositivity rates for hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants were studied. Mean differences (MD) in maternal HBV DNA levels were reviewed. Finally two randomised controlled trials (RCTs) and four non-randomised controlled trials (NRCTs) were left for analysis which included 576 mothers in total, of whom 306 received telbivudine treatment and 270 did not receive any drug. All newborns received hepatitis B vaccine (HBVac) and hepatitis B immunoglobulin (HBIG) after birth. The seropositivity rate for HBsAg or HBV DNA was significantly lower in the telbivudine group, both at birth and at 6--12 months follow up. Meanwhile, maternal HBV DNA levels prior to delivery were significantly lower in the telbivudine group. In addition, the frequency of serum creatine kinase (CK) elevation was similar in the two groups. Our meta-analysis provides preliminary evidence that telbivudine application in late pregnancy is effective in the interruption of intrauterine HBV infection, with no significant adverse effects or complications. More high quality, well-designed, double-blinded, randomised controlled and large size clinical trials are needed for further investigation and more convincing results in the future.     

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.     

Seroepidemiology of hepatitis B virus infection and high rate of response to hepatitis B virus Butang vaccine in adolescents from low income families in Central Brazil

In order to evaluate the seroepidemiology and response to Butang vaccine in adolescents from low income families in Central Brazil, blood samples of 664 adolescents were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) markers, and multiple logistical regression analysis was carried out to determine variables associated with hepatitis B virus (HBV) infection markers. further, three 20 microg Butang vaccine doses were offered to all susceptible individuals (n = 304). Among those who accepted them (n = 182), the seroresponse was evaluated in 170 individuals by quantitative anti-HBs. an overall hbv prevalence of 5.9% was found: four adolescents were HBsAg positive, 24 were anti-HBc, anti-HBs-reactive, and 11 were anti-HBc only. The analyse of risk factors showed that age 16-19 years, place of birth outside Goiás, school B and body piercing were statistically associated with HBV infection markers (p < 0.05). All 170 adolescents responded to Butang, and a geometric mean titer (gmt) of 4344 mUI/ml was obtained. these results reinforce the importance of hepatitis b vaccine in adolescents despite of the hbv regional endemicity, and suggest that three doses of 20 microg of the Butang should guarantee protective anti-hbs levels to individuals at a critical time for hepatitis b acquiring such as latter adolescence and adulthood.     

Prevalence and correlates of hepatitis C virus infection among inmates entering the California correctional system

To estimate the prevalence and predictors of hepatitis C virus (HCV) infection among inmates, a cross-sectional survey was conducted in 1994 among inmates entering six reception centers of the California Department of Corrections. Discarded serum samples were tested for antibodies to human immunodeficiency virus (HIV), HCV, hepatitis B core, and hepatitis B surface antigen (HBsAg). Of 4,513 inmates in this study, 87.0% were men and 13.0% were women. Among male inmates, 39.4% were anti-HCV-positive; by race/ethnicity, prevalences were highest among whites (49.1%). Among female inmates, 53.5% were anti-HCV-positive; the prevalence was highest among Latinas (69.7%). In addition, rates for HIV were 2.5% for men and 3.1% for women; and for HBsAg, 2.2% (men) and 1.2% (women). These data indicate that HCV infection is common among both men and women entering prison. The high seroprevalence of anti-HCV-positive inmates may reflect an increased prevalence of high-risk behaviors and should be of concern to the communities to which these inmates will be released.     

Hydrogel-delivered GM-CSF overcomes nonresponsiveness to hepatitis B vaccine through the recruitment and activation of dendritic cells

The standard hepatitis B surface Ag (HBsAg) vaccine fails to induce anti-hepatitis B surface Abs in 5-10% of healthy subjects, a phenomenon known as HBsAg nonresponsiveness, which is closely related to HLA class II alleles and impaired Th cell responses to HBsAg in these subjects. We hypothesized that GM-CSF, a potent adjuvant in enhancing the Ag-presentation activity of APCs, might help to generate Th cell responses in nonresponders, subsequently providing help for B cells to produce anti-hepatitis B surface Abs. We used a thermosensitive biodegradable copolymer (hydrogel) system to codeliver HBsAg and GM-CSF to achieve maximal local cytokine activity at the injection site. In responder mouse strains, hydrogel-formulated HBsAg plus GM-CSF (Gel/HBs+GM) vaccine elicited much greater anti-hepatitis B surface Ab titers and Th cell proliferative responses than a commercial aluminum-formulated HBsAg vaccine or free HBsAg. The adjuvant effect of the Gel/HBs+GM vaccine was dependent upon the local release of GM-CSF. More importantly, the Gel/HBs+GM vaccine elicited high HBsAg-specific Ab titers and Th cell responses in B10.M mice, a mouse strain that does not respond to the current HBsAg vaccine because of its H-2 haplotype. Analysis of the draining lymph nodes of Gel/HBs+GM vaccine-treated mice revealed an elevated number of CD11c(+) dendritic cells showing enhanced expression of MHC class II and a variety of costimulatory molecules. These results demonstrate that hydrogel-formulated GM-CSF might represent a simple and effective method to generate next-generation hepatitis B virus vaccines for inducing anti-hepatitis B surface Abs in nonresponders.