Objective:b> To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods:b> On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ² test, t test, unconditional logistic regression and interaction analyses. Results:b> The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion:b> The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.
Female ; Follow-Up Studies ; HIV Infections/immunology* ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/administration & dosage* ; Humans ; Immunization Schedule ; Male

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.
Animals ; Hepatitis B Core Antigens ; genetics ; immunology ; Immunity, Cellular ; immunology ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Vaccines, Virus-Like Particle ; genetics ; immunology

China ; Hepatitis B virus ; immunology ; History, 20th Century ; Humans ; Molecular Biology ; history ; Orthomyxoviridae ; immunology ; Viral Vaccines ; immunology ; Virology ; history

<b>OBJECTIVEb>To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination.

<b>METHODSb>Antibody against hepatitis B surface antigen (anti-HBs) were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1∶1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination.

<b>RESULTSb>The positive rates of anti-HBs response to primary vaccination were 97.39% (224/230, 95% CI: 94.41%-99.04%) in the booster group and 53.91% (124/230, 95% CI: 47.24%-60.48%) in the control group (P<0.05), 5 years after the primary vaccination. Geometric mean concentration (GMC) of anti-HBs were 1 140.02 (887.46-1 464.46) mIU/ml in the booster group and 11.53 (8.73-15.23) mIU/ml in the control group (P<0.05). The prevalence rates of breakthrough HBV infection were 0.87% (2/230) in the booster group and 2.17%(5/230) in the control group (P>0.05). RESULTS from the multivariable analysis showed that the booster doses (OR=38.75, 95%CI: 16.23-92.54) and the level of anti-HBs after the primary vaccination (OR =3.06, 95%CI:1.51-6.17) were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination (P<0.05).

<b>CONCLUSIONb>Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.

Antibody Formation ; Case-Control Studies ; Child ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Hepatitis B virus ; Humans ; Immunization, Secondary ; Infant ; Prevalence ; Treatment Outcome ; Vaccination

<b>OBJECTIVEb>To investigate the risk factors for mother-to-child transmission of hepatitis B virus (HBV) and the efficacy of hepatitis B immunoprophylaxis in children at high risk of hepatitis B.

<b>METHODSb>A questionnaire survey was performed on 539 HBsAg-positive mothers and their 551 children (aged from 6 months to 5 years) at high risk of hepatitis B. Serum markers of hepatitis B in the children at high risk of hepatitis B were measured. Univariate logistic regression analysis was used to investigate the risk factors for mother-to-child transmission of HBV.

<b>RESULTSb>The rate of hepatitis B vaccination in the children at high risk of hepatitis B was 100%, and 96.6% received injections of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG). The HBsAg positive rate showed no significant differences between different age groups. The HBsAb positive rate gradually decreased with the increasing age (P<0.01). The children born to HBsAg- and HBeAg-positive mothers had a significantly higher hepatitis B infection rate than those born to HBsAg-positive mothers (15.1% vs 0.2%; P<0.01). The high-risk children who received hepatitis B vaccination alone had a significantly higher hepatitis B infection rate than those who received both hepatitis B vaccine and HBIG injections (28.6% vs 2.8%; P<0.01).

<b>CONCLUSIONSb>The HBsAb positive rate gradually decreases with the increasing age in children at high risk of hepatitis B. Maternal HBsAg and HBeAg positivity and the absence of HBIG combined with hepatitis B vaccine injections for children at high risk of hepatitis B are the risk factors for mother-to-child transmission of HBV.

Child, Preschool ; Female ; Hepatitis B ; etiology ; prevention & control ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B Vaccines ; immunology ; Hepatitis B e Antigens ; analysis ; Humans ; Immunoglobulins ; immunology ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Male ; Risk Factors

<b>INTRODUCTIONb>In 2006, Singapore adopted the universal hepatitis B immunoglobulin (HBIg) policy. Since then, all infants of hepatitis B surface antigen (HBsAg)-positive mothers receive HBIg, irrespective of maternal hepatitis B e antigen (HBeAg) status. However, the benefits of HBIg for infants of HBeAg-negative mothers are unclear. We compared the vertical transmission rates among children of HBeAg-negative mothers who were given HBIg versus a retrospective cohort who were not given HBIg, to determine its protective effect.

<b>METHODSb>This observational study involved pregnant HBsAg-positive women seen at National University Hospital, Singapore, between June 2009 and December 2013. If the infants of these mothers completed the recommended vaccination schedule, they were recruited into the study, along with their older siblings. Serological testing for the children was performed three months after completion of the last dose of vaccine, and hepatitis B virus (HBV) surface gene sequencing was carried out if HBV DNA was detected.

<b>RESULTSb>A total of 111 infants and 47 siblings were recruited. 2 (1.5%) children were found to have vertical transmission despite receiving HBIg, while no incidences of vertical transmission were found among the historical controls who did not receive HBIg (p = 1.00).

<b>CONCLUSIONb>The overall effectiveness of the hepatitis B vaccination programme for children of HBsAg-positive mothers was high, regardless of HBIg administration. The addition of HBIg did not appear to confer additional benefits, in terms of vertical transmission rate, among infants born to HBeAg-negative mothers.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; administration & dosage ; Hepatitis B virus ; Humans ; Immunoglobulins ; immunology ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Male ; Mutation ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Retrospective Studies ; Siblings

<b>OBJECTIVEb>To access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults.

<b>METHODSb>A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6-months schedule: 20 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively.

<b>RESULTSb>A total of 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24.

<b>CONCLUSIONb>Anti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.

Adolescent ; Adult ; Animals ; Body Mass Index ; CHO Cells ; China ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; classification ; Humans ; Immunization, Secondary ; Male ; Middle Aged ; Multivariate Analysis ; Pichia ; Risk Factors ; Saccharomyces cerevisiae ; Seroconversion ; Vaccination ; Young Adult

<b>OBJECTIVEb>To investigate the epidemic status of Hepatitis B in children aged 1-14 in 3 counties of Guangdong province in 2013, and to evaluate the effect of hepatitis control in children aged 1-14 after hepatitis B vaccine was integrated into the national immunization program in 2002 and catch-up vaccination was conducted from 2009 to 2011.

<b>METHODSb>A multi-stage stratified random sampling was designed to survey 1 621 children aged 1-14 in rural area of Nanxiong county, Haifeng county and Xinxing county by questionnaires including general information, medical history and risk factors. The samples were tested with chemiluminescence method to detect hepatitis B virus (HBV) surface antigen (HBsAg), antibody to HbsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc). Chi-square test was used to compare the positive rate of HBV serum markers in different age groups, vaccine histories, birth weight and HBV infection status of mother.

<b>RESULTSb>Among the children aged 1-14 in 3 counties rural regions of Guangdong province, the positive rate of HBsAg, anti-HBs, and anti-HBc was 1.11% (18/1 621), 60.69% (982/1 618) and 1.92% (31/1 617), respectively. The HBsAg positive rate of vaccinated children (0.84%, 13/1 547) was lower than that of unvaccinated children (1/13) or children with unknown vaccination status (6.56%, 4/61) (χ² = 22.64, P < 0.001). The HBsAg positive rate (0.45%, 5/1 118) of the children with birth-dose given within 24 hours was lower than those that of children given beyond 24 hours (2.63%, 61/190) (χ² = 10.21, P < 0.001). The HBsAg positive rate (5/18) of children with birth weight under 2 kilogram was higher than that of children with birth weight above 2 kilogram (0.78%, 12/1 548) (χ² = 120.8, P < 0.001). The HBsAg positive rate of children born to HBsAg-positive mothers (2.80%, 3/107) was higher than that of children born to HBsAg-negative mothers (0.21%, 1/470) (χ² = 8.50, P = 0.004). With the age increasing, the coverage and timely birth-dose coverage of Hepatitis B vaccine (HepB) decreased, and the positive rate of anti-HBs gradually decreased.

<b>CONCLUSIONb>After the catch-up vaccination was conducted in unvaccinated children aged 1-14 years from 2009 to 2011, the HBsAg and anti-HBc positive rate decreased, while the anti-HBs positive rate increased significantly.

Adolescent ; Birth Weight ; Child ; Child, Preschool ; China ; epidemiology ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; Humans ; Immunization Programs ; Infant ; Risk Factors ; Rural Population ; Seroepidemiologic Studies ; Surveys and Questionnaires

Child ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Vaccines ; administration & dosage ; therapeutic use ; Humans ; Patient Acceptance of Health Care ; Vaccination

<b>OBJECTIVEb>To compare the antibody response between adults with hepatitis B virus (HBV) core antibody (anti-HBc) single positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine(HepB).

<b>METHODSb>Adults aged from 18 to 49 who were both negative for HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs), but positive for anti-HBc and narrated no history of HepB immunization by themselves, were selected as single anti-HBc positive group ('anti-HBc alone'). Adults who were negative for HBsAg, anti-HBs and anti-HBc, with age differences within 2 years, and same gender under the 1 : 1 matching program, were selected to form the control group. Both groups were vaccinated on 0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary immunization were revaccination on 0-1-6 schedule. Response rates and geometric mean concentrations (GMC) between the two groups were compared.

<b>RESULTSb>In total, the number of anticipants were 228 pairs. Rates on non-response, low-response, normal-response and high-response after the primary immunization were 8.77% , 11.84%, 31.14% and 48.25% in the control group respectively. The corresponding rates were 8.33%, 30.70%, 35.96% and 25.00% in the 'anti-HBc alone'. The rate of low-response in the control group was lower than that in the 'anti-HBc alone' (χ(2) = 22.28, P < 0.01), while the rate of high-response was higher than that in the control group (χ(2) = 24.43, P < 0.01). GMC of anti-HBs in the control group (534.07 mIU/ml) was higher than that in the 'anti-HBc alone' (183.99 mIU/ml) (u = 4.42, P < 0.01). The anti-HBs conversion rates were 82.35% and 41.18% in the control group and in the 'anti-HBc alone' respectively after the first-dose revaccination, but increased to 90.00% and 82.35% after the third-dose revaccination. The anti-HBs conversion rates in the control group were higher than that in the 'anti-HBc alone' after the first-dose revaccination (P < 0.05), while there was no difference seen between the two groups after the third-dose revaccination (P > 0.05).

<b>CONCLUSIONb>Immune response in the anti-HBc positive adults after primary immunization was weaker than that in common adults. However, immune response induced by HepB was enough to prevent them from infecting HBV. The rates of response showed an obvious increase after revaccination, hence the same HepB immunization strategy could be used.

Adolescent ; Adult ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization, Secondary ; Middle Aged ; Vaccination ; Young Adult