Hepatitis B is a global public health concern. Inducing hepatitis B surface antibody (HBsAb) through vaccination is a crucial preventive strategy. However, individuals show varying immune responses to the hepatitis B vaccine. Based on HBsAb levels, individuals can be categorized as high responders, low responders, or non-responders. T cells and their subsets play critical roles in modulating this response, and the composition of the T cell receptor (TCR) repertoire also influences immune responsiveness. Investigating the characteristics of T cells, their subsets, and TCR repertoires in individuals with differential responses post-vaccination may provide theoretical guidance for optimizing vaccine design and immunization strategies.
Humans ; Hepatitis B Vaccines/immunology* ; Hepatitis B/immunology* ; Vaccination ; Hepatitis B Antibodies/blood* ; T-Lymphocytes/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Hepatitis B Surface Antigens/immunology* ; T-Lymphocyte Subsets/immunology*

Objective: 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: 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: 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: 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

Objective: Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection. Methods: Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted. Results: A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination. Conclusions Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.
Adolescent ; Child ; Child, Preschool ; China ; Female ; Hepatitis A ; immunology ; Hepatitis A Antibodies ; blood ; Hepatitis A Vaccines ; administration & dosage ; Humans ; Immunity, Active ; Infant ; Male ; Models, Statistical ; Vaccination ; statistics & numerical data

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

OBJECTIVETo examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination.

METHODSAntibody 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.

RESULTSThe 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).

CONCLUSIONPrograms 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

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim(TM), Epaxal(R), or Havrix(R), 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim(TM), Epaxal(R), and Havrix(R), respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim(TM), Epaxal(R), and Havrix(R) respectively. Avaxim(TM) was significantly more immunogenic than Epaxal(R) and Havrix(R), whereas there were no significant differences in antibody responses between Epaxal(R) and Havrix(R). Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470)
Adolescent ; Antibody Formation ; Female ; Hepatitis A/immunology/*prevention & control ; Hepatitis A Antibodies/blood ; Hepatitis A Vaccines/adverse effects/*immunology ; Humans ; Male ; Republic of Korea ; Vaccines, Inactivated/adverse effects/immunology ; Young Adult

OBJECTIVETo 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.

METHODSA 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.

RESULTSThe 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).

CONCLUSIONSThe 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

INTRODUCTIONIn 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.

METHODSThis 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.

RESULTSA 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).

CONCLUSIONThe 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

The rapid mutation and widely spread of duck hepatitis A virus (DHAV) lead to the vast economic loss of the duck industry. To prepare and evaluate bivalent inactivated vaccine laboratory products of DHAV, 6 strains were screened from 201 DHAV-1 strains and 38 DHAV-3 strains by using serotype epidemiological analysis in most of the duck factory. Vaccine candidate strains were selected by ELD50 and LD50 tests in the 6 strains. Continuously passaged, the 5th passaged duck embryos bodies grinding fluid was selected as vaccine virus seeds. The virus seeds were treated with formaldehyde and water in oil in water (W/O/W) emulsions, making into three batches of two bivalent inactivated vaccine laboratory products. The safety test, antibody neutralization test, challenged protection and cross immune protection experiment suggested that the vaccines possessed good safety, and neutralizing antibodies were detected at 7th day and the challenged protection rate reached 90% to 100% at the 14th and 21st day. Moreover, immune duration of ducklings lasted more than five weeks. However, cross-immunity protection experiments with DHAV-SH and DHAV-FS only had 20%-30%. The two bivalent inactivated vaccine laboratory products of duck viral hepatitis were effective and reliable, providing a new method as well as a new product for DHAV prevention and control.
Animals ; Antibodies, Neutralizing ; blood ; Ducks ; virology ; Hepatitis Virus, Duck ; Hepatitis, Viral, Animal ; prevention & control ; virology ; Neutralization Tests ; Picornaviridae Infections ; prevention & control ; veterinary ; Poultry Diseases ; prevention & control ; virology ; Vaccines, Inactivated ; immunology ; Viral Hepatitis Vaccines ; immunology