Hepatitis B-CpG Vaccine Series for Healthcare Workers Who Are Hepatitis B Vaccine Nonresponders.

This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504.

Persistence of antibodies 5 years after hepatitis B vaccination in preterm birth children: A retrospective cohort study using real-world data.

Previous studies did not provide substantial evidence for long-term immune persistence after the hepatitis B vaccine (HepB) in preterm birth (PTB) children. Consequently, there is ongoing controversy surrounding the booster immunization strategy for these children. Therefore, we conducted a retrospective cohort study to evaluate the disparities in immune persistence between PTB children and full-term children. A total of 1027 participants were enrolled in this study, including 505 PTB children in the exposure group and 522 full-term children in the control group. The negative rate of hepatitis B surface antibody (HBsAb) in the PTB group was significantly lower than that in the control group (47.9% vs. 41.4%, p = .035). The risk of HBsAb-negative in the exposure group was 1.5 times higher than that in the control group (adjusted odds ratio [aOR] = 1.5, 95% confidence interval [CI]: 1.1-2.0). The geometric mean concentration (GMC) of HBsAb was much lower for participants in the exposure group compared to participants in the control group (9.3 vs. 12.4 mIU/mL, p = .029). Subgroup analysis showed that the very preterm infants (gestational age <32 weeks) and the preterm low birth weight infants (birth weight <2000 g) had relatively low GMC levels of 3.2 mIU/mL (95% CI: 0.9-11.1) and 7.9 mIU/mL (95% CI: 4.2-14.8), respectively. Our findings demonstrated that PTB had a significant impact on the long-term persistence of HBsAb after HepB vaccination. The very preterm infants (gestational age <32 weeks) and the preterm low birth weight infants (birth weight <2000 g) may be special populations that should be given priority for HepB booster vaccination.

Hepatitis B vaccine responders show higher frequencies of CD8+ effector memory and central memory T cells compared to non-responders.

Hepatitis B (HB) infection is a major global health problem. There is limited knowledge about HB vaccination-induced immune memory responses. We compared the frequency of CD8+ memory T cell subsets between responders (RSs) and non-responders (NRs) to HB vaccination. Blood samples were collected from RSs and NRs. PBMCs were cultured in the presence of Hepatitis B surface antigens (HBsAg) and PHA for 48 h to restimulate CD8+ memory T cells and T cell memory subsets were detected by flow cytometry using memory cell markers. The frequency of TEM, TCM, and TCM hi was significantly higher in responders compared to non-responders (p = 0.024, 0.022, and 0.047, respectively). Additionally, we report a positive correlation between the frequency of TEM cells in RSs with age and anti-HBsAb level (p = 0.03 and rs = 0.5; p = 0.01 and rs = 0.06). Responders display a higher level of CD8+ T cell-mediated immunity. Therefore, we suggest a possible defect in the formation of immunological CD8+ memory T cells in NRs and it may reduce antibody production compared to the RSs, although more experiments are needed.

Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Assessment of prevalence and risk factors associated with Hepatitis B virus infection among blood donors in Mogadishu Somalia.

BACKGROUND: The Hepatitis B virus (HBV) is transmitted through contaminated blood or bodily fluids. Globally, over 81 million blood units are donated annually, a crucial therapeutic procedure without alternatives. However, blood-borne infections, including HBV, pose a significant hurdle to safe transfusions, especially in HBV-endemic regions like Somalia with limited screening. Therefore, this study aims to estimate the prevalence of Hepatitis B virus infection and identify risk factors associated with it among blood donors in Mogadishu, Somalia. METHOD: A hospital-based cross-sectional study was conducted between February and April 2023. Research tools included a 5-ml blood sample and a structured questionnaire. The presence or absence of HB markers was determined using a multi-HB rapid test and CDC's HB marker interpretation guideline. Logistic regression was used in univariate and multivariate models to identify risk factors associated with HBV infection, with significance set at a p-value < 0.05 in the final model. RESULT: A total of 494 blood donors were recruited for this study; 93.9% were male, with a mean age of 31.5 (SD = 8.11). The prevalence of Hepatitis B virus (HBV) infection among blood donors was 9.7%, with a 95% CI of 7.1-12.3. In multivariable logistic regression, those with a monthly income of less than 200 USD (AOR = 5.20, 95% CI = 1.61-16.79), those with an income between 200 and 400 (AOR = 3.59, 95% CI = 1.38-9.34), Jobless blood donors (AOR = 3.78, 95% CI = 1.17-12.20), those in business occupations (AOR = 3.35, 95% CI = 1.24-9.08), those with a history of STDs (AOR = 4.83, 95% CI = 2.03-11.50), those without a history of HB vaccine (AOR = 13.81, 95% CI = 2.46-77.41), those with a history of tooth extraction (AOR = 6.90, 95% CI = 2.66-17.88), and those who shared sharp equipment (AOR = 2.90, 95% CI = 1.07-7.82) were more likely to become infected with the Hepatitis B virus (HBV) compared to their counterparts. CONCLUSION: This study highlights a high prevalence of Hepatitis B virus (HBV) infection. Implementation efforts against HBV infection should specifically focus on low-income individuals, the jobless, and donors with a history of STD to mitigate the burden of HBV infection and promote safer blood donation. In addition, discouraging the sharing of sharp equipment, improving infection control practices during tooth extraction procedures, and enhancing HB vaccination uptake, particularly among individuals lacking a history of HB vaccine, is highly recommended.

Hepatitis B vaccine effectiveness among vaccinated children in Africa: a systematic review and meta-analysis.

BACKGROUND: Globally, 257 million people have chronic hepatitis. Even though a safe and effective prophylactic vaccine against HBV infection has been available, it causes significant morbidity and mortality. HBV vaccines were designed to improve or modulate the host immune responses. The effectiveness of the vaccine is determined by measuring serum hepatitis B surface antibody (Anti-HBs) level. Therefore, this systematic review aimed to evaluate the effectiveness of hepatitis B vaccine among vaccinated children. METHODS: Preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines was applied for systematically searching of different databases. Only cross-section studies measuring the level of anti-HBs of vaccinated children were included. The seroprotective level with anti-HBs > 10mIU/ml was extracted. The meta-analysis was performed using statistical software for data sciences (STATA) version 14. Effectiveness estimates were reported as a proportion of anti-HBs level. The heterogeneity between studies was evaluated using the I2 test, and I2 > 50% and/or P < 0.10 was considered significant heterogeneity. Significant publication bias was considered when Egger's test P-value < 0.10. The new castle Ottawa scale was used to assess the quality of the studies. RESULTS: A pooled sample size of the included papers for meta-analysis was 7430. The pooled prevalence of seroprotected children was 56.95%, with a heterogeneity index (I2) of 99.4% (P < 0.001). 35% of the participants were hypo-responders (10-99mIU/ml) and 21.46% were good responders (> 100mIU/ml). Based on subgroup analysis using country of studies conducted, the highest prevalence of anti-HBs was 87.00% (95% CI: 84.56, 89.44), in South Africa, and the lowest was 51.99% (95% CI: 20.41-83.58), with a heterogeneity index I2 = 70.7% (p = 0.009) in Ethiopia. CONCLUSION AND RECOMMENDATIONS: Hepatitis B vaccine seroprotective level in the current pooled analysis have suboptimal, which failed to demonstrate consistent effectiveness for global hepatitis B virus elimination plan in 2030. Using consistent age group may have a significant value for the decision of the HB vaccine effectiveness. A significant heterogeneity was observed both in studies conducted in Ethiopia and Egypt. Therefore, the impact of HB vaccination on the prevention of hepatitis B virus infection should be assessed regularly in those countries. Future meta-analysis is needed to investigate all possible vaccines in a separate way of reviewing, which will lead to a strong conclusion and recommendations.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Hepatitis B antibody levels after different doses of hepatitis B vaccination: a retrospective study based on hospitalized children.

Many studies have investigated the positivity rate of hepatitis B surface antibody (HBsAb) after hepatitis B vaccine (HepB) immunization. However, the antibody level, assessed monthly or at more frequent intervals after each of the three doses, particularly within the first year after birth, has not been previously reported. To elucidate the level of antibody formation at various times after vaccination, the current study used the available detection data of HBsAb in hospitalized children to analyze the HBsAb level after immunization combined with their vaccination history. Both the positivity rate and geometric mean concentration (GMC) increased sequentially with immunization doses, reaching their peaks earlier after the third dose than after the first two doses, and the rate of HBsAb positivity was able to reach 100% between 11 and 90 days after completing the three doses of HepB. Within one year after receiving the three doses, the antibody positivity rate and GMC were maintained above 90% and 100 mIU/mL, respectively, and subsequently steadily declined, reaching the lowest value in the 9th and 10th years. The current findings reveal, in more detail, the level of antibody formation at different times following each dose of HepB in hospitalized children, particularly in the age group up to one year after vaccination. For the subjects of this study, we prefer to believe that the proportion of HBsAb non-response should be less than 5% after full immunization with HepB, provided that the appropriate time for blood collection is chosen.

PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.

OBJECTIVE: The main objective of this article is to review the immunogenicity and safety of the 3-antigen recombinant hepatitis B vaccine (3A-HepB) in adults. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2000 to June 2022) with the search terms hepatitis B vaccine and 3-antigen. Other resources included the Centers for Disease Control and Prevention, conference abstracts of liver meetings, the prescribing information, and the manufacturer's website. STUDY SELECTION AND DATA EXTRACTION: All English-language articles of studies assessing the immunogenicity and safety of 3A-HepB in humans were included. DATA SYNTHESIS: The 3A-HepB is licensed to prevent infection caused by all known subtypes of the hepatitis B virus in adults. It contains 3 hepatitis B surface antigens. The 3A-HepB has been shown to be noninferior to a single-antigen hepatitis B vaccine (1A-HepB). It is administered intramuscularly as a 3-dose series at 0, 1, and 6 months. The most commonly reported local reactions were injection site pain and tenderness, and the most commonly reported systemic reactions were headache, fatigue, and myalgia. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The introduction of 3A-HepB represents another step toward reducing the rates of new hepatitis B infections. However, clinical trials are needed to assess the immunogenicity of 3A-HepB in individuals at high-risk of nonresponse or low response to 1A-HepB, such as those with renal or hepatic impairment and those with altered immunocompetence. CONCLUSIONS: The 3A-HepB represents another vaccine to prevent hepatitis B in adults. It is safe and immunogenic but is associated with more adverse reactions than 1A-HepB.

Toward reaching hepatitis B goals: hepatitis B epidemiology and the impact of two decades of vaccination, Georgia, 2021.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece.

OBJECTIVES: Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. STUDY DESIGN: This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. METHODS: A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. RESULTS: Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52-8.14], pneumococcal disease: 15.73 [10.98-22.52], HZ: 17.01 [9.05-31.96], tetanus: 23.93 [16.20-35.35], measles: 33.47 [16.85-66.47], and hepatitis B: 73.92 [17.47-312.74]). Being well-informed about each vaccine was also a predictor of its uptake. CONCLUSIONS: Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage.

Bad Liver and a Broken Heart: Hepatitis B in the Newborn.

Hepatitis B viral infection is a significant source of morbidity and mortality worldwide. The United States has experienced a precipitous drop in acute hepatitis B infection after the introduction and widespread adoption of recombinant vaccines. Neonates experience significant risk from both vertical and horizontal hepatitis B exposure during a period of immaturity of the innate and adaptive immune systems. Acquisition of hepatitis B virus at or near birth confers the highest lifetime risk of chronic infection and subsequent complications including liver cirrhosis and hepatocellular carcinoma. Pregnant women should be screened for the presence of hepatitis B surface antigen, indicating acute or chronic infection, and, if positive, hepatitis B viral deoxyribonucleic acid, allowing for quantification of viral load. The development of highly effective and safe recombinant vaccines allows partial protection of late preterm and term neonates immediately after birth. Additionally, administration of hepatitis B immune globulin in the setting of suspected or confirmed exposure supplements the immune response and decreases the risk of chronic infection. The optimal timing of vaccination is later in low-birth-weight neonates due to the aforementioned immune system immaturity. Health care providers serving neonates must familiarize themselves with national guidelines regarding hepatitis B vaccination and hepatitis B immune globulin therapy. Understanding the risks of infection and the evidence basis supporting vaccination and immunotherapy will allow providers to educate families and support decision-making, with the potential to eradicate this vaccine-preventable illness in our lifetime.

Vaccines and Autoimmunity-From Side Effects to ASIA Syndrome.

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study.

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable in  hepatitis B e-antigen (HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated. This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety. No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group. Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration: ChiCTR1800016173.

A booster hepatitis B vaccine for children with maternal HBsAg positivity before 2 years of age could effectively prevent vaccine breakthrough infections.

BACKGROUND: The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection. METHODS: Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs. RESULTS: The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected. CONCLUSIONS: After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.

Antivenoms, hepatitis B vaccine and oral polio vaccine can be considered for storage and handling outside the cold chain following the innovative 'controlled temperature chain' approach.

Possible applicability of controlled temperature chain (CTC) for selected antisera and vaccines was evaluated. Bivalent oral polio vaccine (OPV), hepatitis B vaccine (HepB vaccine; monovalent and combined) and antisera (lyophilized and liquid scorpion-antivenom and liquid snake-antivenom) were tested. Samples were stored at accelerated (35 ± 5 °C) and freezing (-25 ± 5 °C) conditions for 24 h, one week and one month in addition to recommended storage condition (2-8 °C), except OPV samples that were tested at accelerated and refrigerated (2-8 °C) conditions compared to recommended storage conditions (-25 ± 5 °C). All samples were tested for potency. Protein content and composition were determined for antisera samples. All vaccine vial-monitors were evaluated. HepB vaccine was subjected to aluminum-content assay, shake test and microscopical examination. No significant change in antisera potency was detectable under accelerated condition for a week. OPV stored in refrigerator for a month and at accelerated condition for 48 h maintained acceptable potency. Monovalent and combined HepB vaccine maintained acceptable potency under accelerated condition for a month and a week, respectively. Freezing adversely affected HepB vaccine. In conclusion, reevaluation of storage conditions of tested products is urgently required; this can reduce storage costs and improves their availability. Other products should be tested for possible CTC applicability.

Hepatitis B immunization data of patients living with HIV/AIDS: a multi-centre study.

OBJECTIVES: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are the two leading viruses that cause the greatest number of virus-related morbidities in the world. HIV/HBV coinfection is correlated with high morbidity and mortality. For this particular reason hepatitis B vaccination is crucial for people living with HIV. METHODS: Patients who are being followed-up for HIV/AIDS and who have received a hepatitis B vaccine in 4 HIV clinics over a 5-year time period have been studied. Our multi-centered, retrospective, cross-sectional and observational study investigates factors that affect hepatitis B vaccination immune response of individuals living with HIV. The patients have been studied for the parameters such as age, sex, CD4 count at the time of diagnosis or vaccination, HIV-RNA levels, comorbidities, vaccine dosage, success of immunization after vaccination, and the demographics of the patients who have and have not developed immunity. RESULTS: Of 645 patients that are being followed-up in our clinics, 158 received hepatitis B vaccine; 39 of these 158 patients have been excluded from the study because they did not fulfil the inclusion criteria. Finally, 119 patients were evaluated in the study, 17 of the patients (14.3%) were females and 102 (85.7%) were males. The median age was 41.11 ± 10.09 (min-max: 18-75). Twenty-three of the patients (19.3%) were at the stage of AIDS during diagnosis while 80.7% were at the stage of HIV infection. Ninety-one of the patients (76.5%) have been administered a single dose hepatitis B vaccine on the standard 0, 1st, 6th month vaccination schedule, whereas 23.5% were administered a double dose on the same vaccination schedule. When further evaluated to find whether the patient was able to develop sufficient immunity (anti-HBs ≥ 10), it was found that the immune response was statistically significantly higher in the patients whose CD4 count was greater than 200 at the time of the first diagnosis and vaccination (p = 0.05 and p = 0.001, respectively). The patients have also been evaluated according to the number of doses they received (1 vs. 2). The immune response of the patients who received two doses was statistically significantly higher (p = 0.041). CONCLUSION: We can conclude that in the patients with CD4 count less than 200 at the time of their diagnosis and vaccination a high dose recombinant hepatitis B vaccine should definitely be administered as the normal dose and higher dose have similar side effect profiles and the higher dose provides greater immunity.

Increased Protection of Earlier Use of Immunoprophylaxis in Preventing Perinatal Transmission of Hepatitis B Virus.

BACKGROUND: Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administering hepatitis B immunoglobulin (HBIG) and birth-dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase protection efficacy. METHODS: We conducted a prospective, multi-center observational study in infants born to mothers with HBV infection, in whom neonatal HBIG and birth dose hepatitis B vaccine were administered within one hour after birth. The infants were followed up for HBV markers at 7-14 months of age. RESULTS: A total of 1140 pregnant women with HBV were enrolled, and 982 infants (9 twins) of 973 mothers were followed up at 9.6 ± 1.9 months of age. HBIG and birth-dose vaccine were administered in newborn infants within a median of 0.17 (0.02-1.0) hours after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of the 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers acquiring HBV. All 9 HBV-infected infants were born to mothers with HBV DNA >2.75 × 106 IU/mL. Maternal HBV DNA levels >2 × 106 IU/mL were an independent risk factor (odds ratio, 10.627; 95% confidence interval, 2.135-∞) for immunoprophylaxis failure. CONCLUSIONS: Earlier use (within 1 hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.

Profiling T cell receptor ß-chain in responders after immunization with recombinant hepatitis B vaccine.

BACKGROUND: T cells with edited T cell receptor ß-chain variable (TRBV) are involved in the immune response to recombinant hepatitis B surface antigen (rHBsAg) vaccine and the production of hepatitis B surface antibody (HBsAb). The immune repertoire (IR) profile and mechanism of vaccination positive responders (VPR) with rHBsAg are not fully understood. METHODS: The IR of six VPRs (HBsAb+, HbsAg-) with rHBsAg vaccination was established by the high throughput sequencing technique and bioinformatics analysis and compared with those in five vaccination negative responders (VNRs) (HbsAb-, HbsAg-) who were also inoculated with rHBsAg. The repertoire features of the BV, BJ and V (CDR3) J genes and immune diversity in peripheral blood mononuclear cells, respectively, were analyzed for each subject. RESULTS: There was no significant difference in sequencing amplification indices of each sample. However, TRBV15/BJ2-3 demonstrated significantly high expression levels in VPR compared to those in the VNR group (both p < 0.05). Further results showed that the BV15/BJ2-5 level was significantly increased for VPR compared to that of VNR group. Interestingly, the motif of CDR3 in TRBV15/BJ2-5 was mostly expressed as "GGETQ" or "GETQ". Additionally, there was no remarkable difference between the two groups of distribution with respect to the different clone expression levels of V (CDR3) J. CONCLUSIONS: The features of IR in the VPR and VNR will contribute to the exploration of the mechanism of the positive response to rHBsAg, and also contribute to development of optimized hepatitis B vaccine, in addition to providing a partial interpretation of the VNR who has a relatively low infection with HBV.