JNJ-64794964 (AL-034/TQ-A3334), a TLR7 agonist, induces sustained anti-HBV activity in AAV/HBV mice via non-cytolytic mechanisms.

JNJ-64794964 (JNJ-4964/AL-034/TQ-A3334), an oral toll-like receptor 7 agonist, is being investigated for the treatment of chronic hepatitis B (CHB), a condition with a high unmet medical need. The anti-hepatitis B (HBV) activity of JNJ-4964 was assessed preclinically in an adeno-associated virus vector expressing HBV (AAV/HBV) mouse model. Mice were treated orally with 2, 6 or 20 mg/kg of JNJ-4964 once-per-week for 12 weeks and then followed up for 4 weeks. At 6 mg/kg, a partial decrease in plasma HBV-DNA and plasma hepatitis B surface antigen (HBsAg) was observed, and anti-HBs antibodies and HBsAg-specific T cells were observed in 1/8 animals. At 20 mg/kg, plasma HBV-DNA and HBsAg levels were undetectable for all animals 3 weeks after start of treatment, with no rebound observed 4 weeks after JNJ-4964 treatment was stopped. High anti-HBs antibody levels were observed until 4 weeks after JNJ-4964 treatment was stopped. In parallel, HBsAg-specific immunoglobulin G-producing B cells and interferon-γ-producing CD4+ T cells were detected in the spleen. In 2/4 animals, liver HBV-DNA and HBV-RNA levels and liver hepatitis B core antigen expression dropped 4 weeks after JNJ-4964 treatment-stop. In these animals, HBsAg-specific CD8+ T cells were detectable. Throughout the study, normal levels of alanine aminotransferase were observed, with no hepatocyte cell death (end of treatment and 4 weeks later) and minimal infiltrations of B and T cells into the liver, suggesting induction of cytokine-mediated, non-cytolytic mechanisms.

Dental auxiliary hepatitis B immunization: a cross-sectional study in the São Paulo state public health system, Brazil, 2018. / Imunização contra hepatite B em auxiliares em saúde bucal: estudo transversal no sistema público de saúde do estado de São Paulo, em 2018.

OBJECTIVE: to investigate dental auxiliaries (DA) hepatitis B immunization in Brazilian National Health System (SUS) services in nine cities in São Paulo State, Brazil, in 2018. METHODS: this was a cross-sectional study based on interviews using a questionnaire as well as evaluation of immunity using the anti-HBs test, evaluation of prior testing, test result and interpretation and guidance provided about hepatitis B. RESULTS: of the 70 registered DA, 35 completed the course of vaccinations, 29 had negative anti-HBs test results, 16 had tested previously, and 43 did not correctly understand their result; there was association (p=0.025) between completed course of vaccinations and receipt of guidance. CONCLUSION: most DA received guidance about hepatitis B; however, a considerable portion did not complete the course of vaccinations and had negative anti-HBs test results; few DA had tested previously nor correctly interpreted the result; evidence was found of an alarming scenario in which there are severe shortcomings in DA hepatitis B immunization.

Hepatitis B seroprevalence in 10-25-year-olds in Mexico - the 2012 national health and nutrition survey (ENSANUT) results.

OBJECTIVES: To estimate hepatitis B virus (HBV) seroprevalence from natural infection or vaccination in 10-25-year-olds in Mexico, using the 2012 National Health and Nutrition Survey (ENSANUT). METHODS: Randomly selected serum samples (1,581) from adolescents and young adults, representative of 38,924,584 Mexicans, were analyzed to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Weighted HBV seroprevalence in the Mexican population and association with sociodemographic variables were calculated. RESULTS: Overall weighted seroprevalence from natural infection (positive for anti-HBs and anti-HBc) was 0.23% (95% confidence interval [95% CI] 0.10-0.52). No HBsAg was detected, indicating no acute or chronic infection. Vaccine-derived immunity (positive ≥ 10.0 mIU/ml for anti-HBs and negative to anti-HBc) was 44.7% (95% CI: 40.2-49.4) overall; lower in persons aged 20-25 years (40.83%) than in persons aged 10-19 years (47.7%). Among the population analyzed, 54.2% (95% CI: 49.6-58.8) were seronegative to HBV (negative for all three markers) and no sociodemographic risk factors were identified. CONCLUSIONS: HBV seroprevalence from natural infection was low. Vaccination-induced immunity was higher among Mexican adolescents than young adults, possibly due to vaccination policies since 1999.

Maternal folic acid supplementation and antibody persistence 5 years after hepatitis B vaccination among infants.

BACKGROUND: Maternal exposure to dietary factors during pregnancy may modulate the immunity of offspring by epigenetic programming. But the relationship between intrauterine environment and persistence of protective antibody after hepatitis B vaccination has not been reported. This study was to investigate the 5-year persistence of protective antibody response after primary hepatitis B vaccination, and its relationship with maternal folic acid supplementation. MATERIALS AND METHODS: A total of 1461 children who completed a 3-dose 10 µg recombinant hepatitis B vaccine at birth and did not infect hepatitis B virus were followed up. Logistic regression and mediation analysis was used to explore the relationship between 5-year persistence of protective antibody and maternal nutrition. RESULTS: Of 1403 children who did not revaccinated during the follow-up, 76.1% had protective hepatitis B surface antibody (anti-HBs) levels. Twenty percent of mothers did not take folate during pregnancy. Mediation analysis showed a total effect of folic acid supplementation on good persistence (odds ratio: 1.10, 95% CI: 1.03-1.17, p = 0.0010), a direct effect was 1.07 (95% CI: 1.01-1.13, p = 0.0128) and an indirect effect was 1.03 (95% CI: 1.00-1.06, p = 0.0672); the proportion of good persistence mediated by primary response was 30.3%. CONCLUSION: This study indicated a good protective anti-HBs persistence at year 5 after 10 µg recombination hepatitis B vaccination in infants. Maternal folic acid supplementation may improve the persistence of protective antibodies through other pathways. Multi-center cohort studies should be conducted to verify this conclusion.

Oral administration of synthetic selenium nanoparticles induced robust Th1 cytokine pattern after HBs antigen vaccination in mouse model.

Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5µg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100µg and 200µg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. CONCLUSIONS: The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias.

[Study on health-seeking behavior and influencing factors among Chinese hepatitis B surface antigen positive adults].

OBJECTIVE: To analyze the characteristics of health-seeking behaviors and related influencing factors of the community-based hepatitis B surface antigen (HBsAg) positive adults, in China. METHODS: Based on the cohort formed by the HBsAg positive patients, in the national sero-survey project in 2006, we conducted a follow-up programs in 2010 and 2014. In the latest follow-up project, we carried out a cross-sectional study to collect information on health-seeking behaviors of the patients. Questionnaires would include information on clinic visits, diagnosis, regular physical examination and treatments,etc. We used the SPSS 18.0 software for data analysis. RESULTS: Totally, 2 478 HBsAg positive adults (≥18 years old) were followed through, with 34.4% (853/2 478) of them had visited the doctors and diagnosed after they were informed the status of HBsAg positivity, in the 2006-sero-survey program. Among patients who ever visiting the clinic, 51.2% (372/727) of them underwent at least medical examination once a year, with 31.5% (229/727) of them received treatment. Furthermore, 34.5% (79/229) of the treated patients adopted the traditional Chinese medicine or medicine for ' liver protection'. 56.8% (130/229) of the treated patients received antiviral drugs. Data from the binary logistic regression showed that the major influencing factors on clinic visits would include: age, level of education received and residencial areas (rural/urban). CONCLUSIONS: Consciousness on health was low in those community-based HBsAg positive people. Standerdized management and clinical treatment programs should be set up accordingly.

Maternal zinc supplementation improves hepatitis B antibody responses in infants but decreases plasma zinc level.

PURPOSE: The World Health Report identifies zinc deficiency as one of the major causes of disease in developing countries, and infants are at particular risk. We aimed to investigate the effect of maternal zinc supplementation on the infant's immune function in a population at risk of deficiency. METHODS: In a randomized, double-blind placebo-controlled trial, mothers were supplemented either with 20 mg/day of elemental zinc (n = 20) or placebo (n = 19) at the beginning of second trimester, which continued until 6 months postpartum. Indicators of the infants' immune function measured included interleukin (IL)-7, thymic size and response to hepatitis B vaccination. RESULTS: Infants born from mothers receiving zinc supplements during pregnancy and postpartum had significantly lower plasma zinc (p < 0.05) but marginally higher IL-7 and antibody responses to hepatitis B vaccination (p < 0.10) than infants born from mothers not receiving zinc. Maternal zinc supplementation showed no negative impact on copper status of mothers or their infants. Maternal zinc supplementation did not influence infant thymic size, but cord blood IL-7 was found positively associated with thymus size at 1 month of age (r = 0.392) and with hepatitis B vaccine response at 6 months of age (r = 0.386). CONCLUSION: Prenatal and postnatal zinc supplementation marginally improved T cell-dependent antibody responses in infants along with IL-7, a cytokine involved in human T cell development and maintaining homeostasis.

Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation.

The rapid occurrence of emerging infectious diseases demonstrates an urgent need for a new preclinical experimental model that reliably replicates human immune responses. Here, a new homozygous humanized human leukocyte antigen (HLA)-A11/DR1 transgenic mouse (HLA-A11(+/+)/DR01(+/+)/H-2-ß2m(-/-)/IAß(-/-)) was generated by crossing HLA-A11 transgenic (Tg) mice with HLA-A2(+/+)/DR01(+/+)/H-2-ß2m(-/-)/IAß(-/-) mice. The HLA-A11-restricted immune response of this mouse model was then examined. HLA-A11 Tg mice expressing a chimeric major histocompatibility complex (MHC) molecule comprising the α1, α2, and ß2m domains of human HLA-A11 and the α3 transmembrane and cytoplasmic domains of murine H-2D(b) were generated. The correct integration of HLA-A11 and HLA-DR1 into the genome of the HLA-A11/DR1 Tg mice (which lacked the expression of endogenous H-2-I/II molecules) was then confirmed. Immunizing mice with a recombinant HBV vaccine or a recombinant HIV-1 protein resulted in the generation of IFN-γ-producing cytotoxic T lymphocyte (CTL) and antigen-specific antibodies. The HLA-A11-restricted CTL response was directed at HLA immunodominant epitopes. These mice represent a versatile animal model for studying the immunogenicity of HLA CTL epitopes in the absence of a murine MHC response. The established animal model will also be useful for evaluating and optimizing T cell-based vaccines and for studying differences in antigen processing between mice and humans.

Immune response in infants after universal high-dose hepatitis B vaccination: A community-based study in Beijing, China.

BACKGROUND: Vaccination of infants beginning at birth is recommended to prevent Hepatitis B virus (HBV) infection in China. Compared to 5 µg/dose vaccine administered in other regions in China, a three-dose HB recombinant yeast vaccine at 10 µg/dose has been administered for infants within 24h after birth, 1 month and 6 months of age in Beijing since 2006. In a community-based retrospective cohort study, factors influencing immunologic vaccine response were evaluated. METHODS: A total of 3670 infants who completed a 3-dose 10 µg recombinant HB vaccine regimen and born to hepatitis B antigen negative mothers were included. The effect on anti-HBs titers of maternal nutrient status, infants' birth condition, growth factors, timeliness of vaccination, dosing interval and the interval until post-vaccination serologic testing (PVST) were evaluated. RESULTS: A total of 3666 infants with no markers of HBV infection were included in analysis. The mean anti-HB titers were 1767.17 mIU/ml. Only 16.9% of the infants completed their PVST within 30-59 days after the final dose of vaccination. Multivariate linear regression analysis showed that delay in PVST (ß=-0.097, p<0.0001) and maternal folic acid supplementation (ß=0.067, p=0.002) were associated with log-transformed anti-HB titers. Also a trend toward significant association was observed between the calcium supplementation of infants and log-transformed anti-HBs titers (ß=0.062, p=0.057). Longer interval between dose 2 and dose 3 was not observed to increase the anti-HB titers after cofactors adjustment. CONCLUSIONS: Our findings illustrate the importance of timing of PVST to avoid unnecessary revaccination. Multi-center large cohort studies should verify the effect and magnitude of folate and calcium supplementation on HB vaccine response.

A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol.

BACKGROUND: Vitamin A supplementation significantly reduces all-cause mortality when given between 6-59 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization. METHODS/DESIGN: In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother-infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (Treg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses. DISCUSSION: Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy. TRIAL REGISTRATION: clinicaltrials.gov NCT01476358.

An assessment of the performance of self-reported vaccination status for hepatitis B, National Health and Nutrition Examination Survey 1999-2008.

OBJECTIVES: We sought to assess the performance of self-reported vaccination with hepatitis B vaccine (HepB) compared with serological status for hepatitis B markers in the general US civilian population. METHODS: Using 1999 through 2008 National Health and Nutrition Examination Survey data, we calculated 3 measures of agreement between self-reported HepB vaccination status and serological status: percent concordance, and positive (PPV) and negative predictive values (NPV) of self-report. Logistic regression was used to identify factors associated with agreement between self-report and serological status. RESULTS: Overall agreement was 83% (95% CI = 82.3, 83.7), NPV of self-report was high (0.95; 95% CI = 0.93, 0.95) and PPV was low (0.53; 95% CI = 0.51, 0.54). Birth year relative to the 1991 recommendation for universal infant HepB vaccination had a strong association with agreement, however, the association was positive for those who reported receiving at least 3 doses and negative for those who reported receiving no doses. CONCLUSIONS: Although the low PPV in our study could be attributable in part to waning of vaccine-induced anti-HBs over time, national adult HepB vaccination coverage may be lower than previously estimated because national estimates usually depend on self-report of vaccine receipt.

Extraction and purification of hepatitis B virus-like M particles from a recombinant Saccharomyces cerevisiae strain using alumina powder.

A recombinant hepatitis B surface antigen (HBsAg) has been produced in the yeast Saccharomyces cerevisiae and used as a vaccine against hepatitis B virus (HBV) infection. The present study aimed to optimize the extraction of recombinant virus-like particles (rVLPs) to develop a simple purification procedure based on gel filtration and high performance size-exclusion chromatography. The findings showed that disruption of yeast cells with alumina powder increased the yield of the total proteins (290mg/l) and rVLPs (1mg/l) compared to the values for glass beads (171mg/l and 0.5mg/l), as estimated by quantitative ELISA. The purification of rVLPs was performed by two consecutive gel filtration chromatographic steps, namely Sephacryl S-200 followed by SEC-250 HPLC. The purified M protein was analyzed by atomic force microscopy and shown to assemble in particles that were able to recognize HBV antibodies in the sera of patients with chronic hepatitis B, providing evidence for their immunoreactivity.

Effects of massage on antibody responses after hepatitis B vaccination.

OBJECTIVE: The aim of this study was to examine whether participation in a 4-week massage intervention is associated with reduced distress and enhanced antibody responses after hepatitis B vaccine in students embarking on academic examinations. METHODS: Seventy medical student volunteers (36 women, 34 men) were randomly assigned to intervention or control groups. Baseline assessments were made of distress, health behaviors, and prevaccination antibodies to hepatitis B surface antigen. Intervention participants received weekly 45-minute massages before an examination period. At the end of the intervention and 1 week before commencing the examination period, all participants received an intramuscular hepatitis B vaccination and repeated the assessments completed at baseline. Serum antibody responses to hepatitis B surface antigen were measured at 2 and 6 weeks postvaccination. RESULTS: Examinations were associated with increased distress in both the massage and the control groups: perceived stress (F(1,67) = 10.64, p = .002), anxiety (F(1,67) = 15.72, p < .001) and negative affect (F(1,66) = 5.80, p = .019); these increases did not differ between the massage and the control groups. Furthermore, massage was associated with lower levels of antibody to hepatitis B surface antigen after vaccination at both time points (F(1,63) = 6.29, p = .015). CONCLUSIONS: These findings indicate that a brief massage intervention did not attenuate emotional distress during an examination period but did result in lowered antibody responses to vaccination. Further research is required to establish whether these effects were attributable to the nature of intervention (i.e., duration and type of massage) and/or its limited relevance to a healthy population confronting a relatively acute stressor such as examinations.

Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor ß and the frequency of regulatory T cells.

Astragalus polysaccharides (APS), extracted from the root of Astragalus membranaceus, a traditional Chinese medicinal herb, have extensive pharmacological and strong immunomodulatory effects. In this study, the potential adjuvant effect of APS on humoral and cellular immune responses to hepatitis B subunit vaccine was investigated. Coadministration of APS with recombinant hepatitis B surface antigen significantly increased antigen-specific antibody production, T-cell proliferation and CTL (cytotoxic T lymphocyte) activity. Production of interferon-γ (IFN-γ), interleukin-2 (IL-2) and IL-4 in CD4(+) T cells and of IFN-γ in CD8(+) T cells were dramatically increased. Furthermore, expression of the genes PFP, GraB, Fas L and Fas were up-regulated; interestingly, expression of transforming growth factor ß (TGF-ß) and the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) were down-regulated. Expression of Toll-like receptor 4 (TLR4) was significantly increased by administration of APS. Together, these results suggest that APS is a potent adjuvant for the hepatitis B subunit vaccine and can enhance both humoral and cellular immune responses via activating the TLR4 signaling pathway and inhibit the expression of TGF-ß and frequency of Treg cells.

Chronic hepatitis B treatment: the cost-effectiveness of interferon compared to lamivudine.

OBJECTIVE: To perform a cost-effectiveness evaluation from the perspective of the Brazilian National Health System of alternatives strategies (i.e., conventional interferon, pegylated interferon, and lamivudine) for the treatment of patients with chronic hepatitis B who present elevated aminotransferase levels and no evidence of cirrhosis at the beginning of treatment. METHODS: A Markov model was developed for chronic hepatitis B (hepatitis B antigen e [HBeAg] positive and negative) with 40 years' time horizon. Costs and benefits were discounted at 5%. Annual rates of disease progression, costs due to complications, and the efficacy of medicines were obtained from the literature. One-way and probabilistic sensitivity analysis evaluated uncertainties. RESULTS: For HBeAg positive patients, peginterferon (48 weeks) resulted in an increase of 0.21 discounted life-years gained compared to interferon (24 weeks). The incremental cost-effectiveness ratio (ICER) converted to US dollars using the 2009 purchasing power parity conversion factor was US$100,752.24 per life-year gained. For HBeAg negative patients, it was observed that interferon (48 weeks) compared with long-term lamivudine presented an increase of 0.45 discounted life-years gained and ICER of US$15,766.90 per life-year gained. In the sensitivity analysis, the ICER was more sensitive to variation in the probability of transition from chronic hepatitis B to compensated cirrhosis, discount rate, and medicine prices. Cost-effectiveness acceptability curve for HBeAg positive (pegylated interferon vs. conventional interferon) and negative (conventional interferon vs. lamivudine) showed that conventional interferon was cost-effective until three times the gross domestic product per capita. CONCLUSIONS: For patients with chronic hepatitis B with elevated aminotransferase levels in the pretreatment and no cirrhosis who were HBeAg positive, pegylated interferon (48 weeks) provided more life-years gained when compared to conventional interferon (24 weeks), and the ICER surpasses the country's buying power, which makes conventional interferon the chosen alternative. For HBeAg negative patients, conventional interferon (48 weeks) compared to lamivudine provided more life-years gained at a favorable ICER.

[Interventional effect of vitamin A supplementation on re-vaccination to hepatitis B virus among rural infants and young children in China].

OBJECTIVE: The objective of this study was to observe the interventional effect of cod liver oil supplementation on re-vaccination to hepatitis B virus (HBV) among infants and young children. METHODS: All 7-36 months old infants and young children, who had been vaccinated with obligatory HBV vaccines routinely by the national technical and administrative procedures for HBV vaccination on children of China, were convened among villages in Linyi, Shandong province, from October 2008 to March 2009. After detection of serum anti-HBV, one hundred children with lower serum anti-HBV were picked out for the randomized, double blinded, placebo controlled vitamin A supplementation study. The children in the intervention group (50 subjects) took 0.5 g condensed cod liver oil (containing 25 000 IU vitamin A and 2500 IU vitamin D(2)) every 15 days for six times. The children in the control group (50 subjects) were given corn oil with same volume. All children were re-vaccinated at the 30th and the 60th day of the experiment. The serum samples were collected from each child at the 90th day of the experiment. Retinol concentration in serum samples was analyzed with HPLC method before and after the intervention. The levels of serum anti-HBs were detected by the electro-chemi-luminescence immunoassay (ECLIA). RESULTS: Total 74 children finished the supplemental experiment and blood collection, 37 subjects in each group, respectively. After intervention, the serum retinol level in the experimental and control group were (404.1 ± 123.1) and (240.8 ± 92.8) µg/L (t = 6.441, P < 0.01), respectively. The serum anti-HBs levels in the experimental and control group were (2737.2 ± 2492.6) and (1199.7 ± 2141.6) U/L (t = 2.846, P < 0.01), respectively. The rate of weak or no-answer case in experimental and control groups was 0.00% (0/37) and 10.81% (4/37) (χ(2) = 4.229, P = 0.040), respectively. CONCLUSION: The results showed that vitamin A supplementation might enhance the re-vaccination reaction against HB vaccine in infants and young children.

Hepatitis B virus infections among children and adolescents in Germany: migration background as a risk factor in a low seroprevalence population.

BACKGROUND: Data on hepatitis B (HB) infection prevalence among children and adolescents in Germany are scarce. We estimated seroprevalence of HB infection and assessed determinants for HB infection among children and adolescents in Germany from a representative population sample. METHODS: From 2003 to 2006, the Robert Koch Institute conducted a nationwide cross-sectional Health Interview and Examination Survey for Children and Adolescents in Germany. Data on age, gender, migration background, and socioeconomic status were collected through questionnaires. A child was defined as having a 2-sided migration background if both parents, or the child and 1 parent, immigrated, and a 1-sided migration background if only 1 parent immigrated. Among children with migration background, a first-generation migrant was defined as born outside Germany; a second-generation migrant was born in Germany. Information on HB vaccination status was obtained from vaccination cards. Serologic samples from participants were tested for anti-hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen. We performed weighted univariable and multivariable logistic regression analyses to assess determinants for HB infection. RESULTS: Of 13,065 participants (3-17 years), 0.5% (95% confidence interval [CI], 0.4-0.7) were anti-HBc positive, among whom 38.7% (95% CI, 20.0-57.5) were hepatitis B surface antigen positive. Two-sided migration background and being a first- or second-generation migrant were significantly associated with anti-HBc positivity (odds ratio [OR]: 8.3, 95% CI: 4.0 ­17.4; OR: 11.0, 95% CI: 3.5-35.0; OR: 3.0, 95% CI: 1.2-7.3). No further determinants were found. CONCLUSIONS: HB infection is rare among children and adolescents in Germany. First- and second-generation migrant children can be considered to be at risk for HB infection, 2-sided migration background or being a first-generation migrant carried the greatest risk. Targeted testing for HB infection and early HB vaccination should be provided to immigrants' children.

Antibody responses in mice stimulated by various doses of the potato-derived major surface antigen of hepatitis B virus.

The ability of potato-derived major surface antigen of hepatitis B virus (P-HBsAg) to elicit antibody responses to different dosages of P-HBsAg ranging from 0.02 to 30 µg administered orally in mice was examined. All immunized groups produced specific serum IgG and fecal IgA antibodies against P-HBsAg, even at low levels (<5 µg), after administration of a 0.5-µg yeast-derived HBsAg (Y-HBsAg; LG Life Sciences, Republic of Korea) booster.

Efficacy of a single dose hepatitis B depot vaccine.

A single dose formulation of a novel hepatitis B vaccine, consisting of an adjuvant emulsion of liposomes in oil was produced at a manufacturing scale and delivered to rabbits. This single dose vaccine generated a significantly higher antibody response than two doses of an alum-adjuvanted control vaccine in the short term, and was as effective as three doses of the control vaccine in the long term.

Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response.

Hepatitis B surface antigen (HBsAg) is known to adsorb to aluminum hydroxide adjuvant (AH) by ligand exchange between its accessible phosphate groups and surface hydroxyl groups of the adjuvant. To study the effect of the binding strength, five vaccines were prepared with AH or four samples of AH that were modified by pretreatment with different concentrations of potassium dihydrogen phosphate. The adsorptive coefficients ranged from 3660 to 250mL/mg based on the Langmuir adsorption isotherm and degrees of elution ranged from 1 to 31% when the vaccines were exposed to interstitial fluid in vitro. When tested in mice the four vaccines containing phosphate-treated AH (PTAH) induced significantly greater antibody responses than the vaccine containing AH, which had the highest adsorptive coefficient and the smallest degree of elution of HBsAg. The results indicated that antibody production is reduced when the antigen is adsorbed too strongly. Thus, the strength of adsorption of the antigen to an aluminum-containing adjuvant can affect the immunogenicity of the vaccine and should be optimized during vaccine formulation.