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Introduction: viral hepatitis B remains a major public health problem around the world, especially in underdeveloped and developing countries. Cameroon shows a grate variability in prevalence of this infection in the country and even within different populations groups. The aim of this study was to determine the prevalence and factors associated with viral hepatitis B infection in the rural area of Dschang., Methods: we conducted a cross-sectional community-based study, involving 551 participants of both genders recruited by a voluntary sampling technique. The biological diagnosis of HBsAg was done by the Immunochromatographic method (PKL® kit of PARAMEDICAL srl laboratories). Positive cases were confirmed by ELISA method (reagent Kit from DIALAB Laboratories)., Results: results show a Viral Hepatitis B prevalence of 5.08% (95% CI: 3.2-6.9). University students were the most infected (11/88) with a positivity rate of 12.50% (95%CI: 5.6-19.4). Only 29/551 participants (5.26%) had received at least one dose of vaccine against the disease and were less infected (3.44%) than the others (5.17%). Age (p=0.000), level of education (p=0.013), occupation (p = 0.002), belief in the traditional healing of hepatitis B (p=0.000) and knowledge about the disease and its contamination roads (p=0.049) were associated with viral hepatitis B., Conclusion: there is a need of intensifying awareness, education, routine screening and vaccination of the population, especially in schools and university milieu to better counteract the infection with hepatitis B virus in our local Communities., Competing Interests: The authors declare no competing interests., (Copyright: Thomas Djifack Tadongfack et al.)

Background: Migrant workers are a susceptible population to the hepatitis b virus (HBV) and a vulnerable spot in China's immunization procedures. There is no free HBV immunization program for migrant workers in China, so understanding migrant workers' motivation to receive the HBV vaccine is the first step in designing effective immunization policies., Methods: A fully specified protection motivation theory (PMT) model of HBV vaccination intention among migrant workers was specified. Data were collected through a cross-sectional survey of 406 migrant workers in three migrant-dense industries in Tianjin, China. Principal component factor analysis was used to produce PMT factors and nested binary logistic regression modeling was applied to assess the associations between protection motivation and HBV vaccination intention of migrant workers., Results: The nested binary logistic regression model suggested that the severity factor and self-efficacy factor were positively related to HBV vaccination intention (OR = 2.15, 95% CI: 1.25-3.71; OR = 2.75, 95% CI: 1.62-4.66) while the response costs was negatively related to the HBV vaccination motivation (OR = 0.50, 95% CI: 0.29-0.83). The socio-demographic variables showed that younger, married and good self-rated health status participants were statistically associated with the intention of taking the HBV vaccine. Sex, education level and income group were not significantly associated with vaccination intention. The migrant-industry variables showed that migrant location had a strong effect on migrant workers' vaccination intention., Conclusion: Socio-demographic, migrant-industry variables and PMT factors (severity, self-efficacy and response costs) were statistically associated with migrant workers' intention to vaccinate. Our results suggest that health policy makers should provide more information to migrants on HBV severity; inform migrant workers on where, when and how to get the HBV vaccine; tap into work organizations as a location for vaccinations; and identify migrant worker subgroups for targeted interventions.

Hepatitis B is a global epidemic that requires carefully orchestrated vaccination initiatives in geographical regions of medium to high endemicity to reach the World Health Organization's elimination targets by 2030. This study compares two widely-used deterministic hepatitis B models-the Imperial HBV model and the CDA Foundation's PRoGReSs-based on their predicted outcomes in four countries. The impact of scaling up of the timely birth dose of the hepatitis B vaccine is also investigated. The two models predicted largely similar outcomes for the impact of vaccination programmes on the projected numbers of new cases and deaths under high levels of the infant hepatitis B vaccine series. However, scenarios for the scaling up of the infant hepatitis B vaccine series had a larger impact in the PRoGReSs model than in the Imperial model due to the infant vaccine series directly leading to the reduction of perinatal transmission in the PRoGReSs model, but not in the Imperial model. Meanwhile, scaling up of the timely birth dose vaccine had a greater impact on the outcomes of the Imperial hepatitis B model than in the PRoGReSs model due to the greater protection that the birth dose vaccine confers to infants in the Imperial model compared to the PRoGReSs model. These differences underlie the differences in projections made by the models under some circumstances. Both sets of assumptions are consistent with available data and reveal a structural uncertainty that was not apparent in either model in isolation. Those relying on projections from models should consider outputs from both models and this analysis provides further evidence of the benefits of systematic model comparison for enhancing modelling analyses., Competing Interests: The authors have declared that no competing interests exist.

Introduction: adequate knowledge on hepatitis B virus (HBV) infection is important among healthcare workers (HCWs) as this impacts the vaccination seeking behaviour. This study sought to assess the knowledge, vaccination status and related factors amongst HCWs in a tertiary facility in Ghana., Methods: an analytical cross-sectional study was conducted amongst full-time HCWs of different categories at the Cape Coast Teaching Hospital, Ghana. Stratified sampling was used to arrive at the number needed for each category of HCW and then simple random sampling to recruit participants. A structured self-administered questionnaire was used. Descriptive statistics and logistics regression were carried out on the data., Results: a total of 303 HCWs participated with 78.07% (n=235) being between 20-30 years, and majority being females (62.38%, n=189). A total of 186 (61.39%) participants had adequate knowledge, mean knowledge score was 4.73/7 (±0.97). About 80% (n=218) had received the 3 doses of HBV vaccine. Among the unvaccinated, cost was the major barrier (62.07%, n=18). Participants who did not know that HBV was more infectious than HIV (aOR=5.31, 95%CI: 1.91-14.77), p<0.001) and those who did not have knowledge that HBV vaccine was effective were more likely to be unvaccinated (aOR=8.63, 95%CI: 2.99-24.94), p<0.0001). The gender and cadre of staff did not show statistical evidence of an association with vaccination status., Conclusion: knowledge on HBV is paramount for all HCWs as well as the importance of receiving the full doses of the hepatitis B vaccines. Barriers to vaccination must be removed to ensure protection of HCWs., Competing Interests: The authors declare no competing interests., (Copyright: Elizabeth Tabitha Botchway et al.)

Introduction: This paper reports 17 years of passive safety surveillance of routine use of the pediatric hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus- Haemophilus influenzae type b-conjugate vaccine (DTPa-HBV-IPV/Hib, Infanrix hexa , GSK)., Methods: Global post-licensure passive surveillance data collected in GSK's central safety database since DTPa-HBV-IPV/Hib's launch (2000) are described., Results: The most common spontaneously reported adverse events (AEs) after DTPa-HBV-IPV/Hib vaccination in children were fever (reporting rate: 7.74/100,000 doses distributed), crying (2.62/100,000), injection site erythema (1.87/100,000) and swelling (1.28/100,000). A review of extensive limb swelling did not reveal any safety concerns. An observed-to-expected analysis did not show an increased risk of sudden death after DTPa-HBV-IPV/Hib vaccination, in line with previous observations. The analyses confirmed that increases in spontaneous reporting proportions of convulsions with/without fever and hypotonic-hyporesponsive episodes after co-administration of DTPa-HBV-IPV/Hib and 13-valent pneumococcal conjugate vaccine remained small and their clinical significance unknown. The most common vaccination errors were mistakes in the vaccination schedule. Reporting of preparation errors (mostly reconstitution) was low and did not impact the vaccine's benefit-risk profile., Conclusions: Seventeen years of post-licensure experience confirm confidence in the safety profile of DTPa-HBV-IPV/Hib in routine use, with a favorable benefit-risk profile in infants and toddlers., Plain Language Summary: What is the context? The cornerstone of childhood vaccination in many countries worldwide is a vaccine that protects against several diseases: diphtheria, tetanus, whooping cough, hepatitis B, polio and Haemophilus influenzae type b infections (such as meningitis). One of these vaccines (the longest on the market) is called Infanrix hexa ; it has been available for infants and toddlers since 2000. After a vaccine is included in a country's routine vaccination program, its safety is constantly checked; this is done in clinical trials and through spontaneous reporting of adverse events after vaccination. It is important to share up-to-date information on the safety of vaccines, particularly since concerns about vaccine safety in parents may lead to lower vaccination rates an disease outbreaks. Here we summarize 17 years of safety data for the Infanrix hexa vaccine. What is new? We analyzed spontaneously reported adverse events after Infanrix hexa vaccinations between 2000 and 2017 The most commonly reported adverse events were fever, crying and injection site redness and swelling An in-depth review of extensive limb swelling after Infanrix hexa vaccination revealed no safety concerns. There was no increased risk of sudden death after Infanrix hexa vaccination, consistent with what was shown in several other studies. As shown previously, seizures were more common when Infanrix hexa was given together with the pneumococcal conjugate vaccine, Prevnar 13, than when it was given alone. What is the take-home message? The large amount of safety data gathered from clinical trials and from spontaneous adverse event reporting during 17 years of routine vaccination with Infanrix hexa supports its continued use in young children.

Aim: To document adherence to influenza, pneumococcal and hepatitis B virus (HBV) vaccination programme in adult type 1 diabetes mellitus (T1DM) patients., Materials and Methods: Observational retrospective study using data obtained from computerized clinical records. We contacted all adult T1DM registered in our database from a tertiary diabetes care hospital. Primary efficacy outcome was to describe influenza, pneumococcal and HBV vaccination status., Results: Three hundred patients were analyzed (male 53%). Mean age was 40.0±14.4years and T1DM duration was 19.7±11.8years. Thirty-five percent of the patients had complementary indications for studied vaccines. Adherence to vaccination program for influenza, pneumococcal and HBV was achieved by 55%, 18% and 17% of the patients, respectively. Only 3% of the subjects were vaccinated against the three microorganisms. Predictor of correct vaccination were: age, shorter diabetes duration, insulin pump treatment, better diabetes control and being a health professional. We detected 17 sick leaves, 127 lost working days and 3 hospitalizations due to flue during the follow-up., Conclusions: The uptake of recommended vaccinations against influenza, pneumococcal and HBV in adult T1DM patients was below desirable levels. A special effort is required to all health professionals to implement immunization among adult people with T1DM. Clinical Trials NCT03478254., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

In 2015, the World Health Organization (WHO) South-East Asia Region (SEAR)* reported an estimated 40 million persons living with chronic hepatitis B virus (HBV) infection and 285,000 deaths from complications of chronic infection, cirrhosis, and hepatocellular carcinoma (1). Most chronic HBV infections, indicated by the presence of hepatitis B surface antigen (HBsAg) on serologic testing, are acquired in infancy through perinatal or early childhood transmission (2). To prevent perinatal and childhood infections, WHO recommends that all infants receive at least 3 doses of hepatitis B vaccine (HepB), including a timely birth dose (HepB-BD) † (1). In 2016, the SEAR Immunization Technical Advisory Group endorsed a regional hepatitis B control goal with a target of achieving hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020, which is in line with the WHO Global Health Sector Strategy on Viral Hepatitis 2016-2021 (2,3). The South-East Asia Regional Vaccine Action Plan 2016-2020 (SEARVAP) (4) identified the acceleration of hepatitis B control as one of the eight regional goals for immunization. The plan outlined four main strategies for achieving hepatitis B control: 1) achieving ≥90% coverage with 3 doses of HepB (HepB3), 2) providing timely vaccination with a HepB birth dose (HepB-BD), 3) providing catch-up vaccination of older children, and 4) vaccinating adult populations at high risk and health care workers (1,4). In 2019, SEAR established a regional expert panel on hepatitis B to assess countries' HBV control status. This report describes the progress made toward hepatitis B control in SEAR during 2016-2019. By 2016, all 11 countries in the region had introduced HepB in their national immunization programs, and eight countries had introduced HepB-BD. During 2016-2019, regional HepB3 coverage increased from 89% to 91%, and HepB-BD coverage increased from 34% to 54%. In 2019, nine countries in the region achieved ≥90% HepB3 coverage, and three of the eight countries that provide HepB-BD achieved ≥90% HepB-BD coverage. By December 2019, four countries had been verified to have achieved the hepatitis B control goal. Countries in the region can make further progress toward hepatitis B control by using proven strategies to improve HepB-BD and HepB3 coverage rates. Conducting nationally representative hepatitis B serosurveys among children will be key to tracking and verifying the regional control targets., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Hepatitis B virus (HBV) infection is one of the major public health problems worldwide. Limited information exists about the epidemiology of HBV infection in Ethiopia. This study aimed to assess sero-prevalence of HBV markers and associated factors in children living in Hawassa City, southern Ethiopia., Methods: A community-based cross-sectional study was conducted among 471 children in Hawassa City, southern Ethiopia from May to September, 2018. A total of 471 children were included in the study using a multistage sampling technique. Data on demographic and risk factors were gathered using structured questionnaires. Blood samples were collected and sera were screened for hepatitis B surface antigen (HBsAg), antibody to core antigen (anti-HBc), and antibody against surface antigen (anti-HBs) using enzyme-linked immunosorbent assay., Results: The sero-prevalence of HBsAg, anti-HBc, and anti-HBs markers among children were 4.4, 19.5 and 20.0%, respectively. Children at higher risk of having HBsAg marker were those who had a history of injectable medications (AOR 5.02, 95% CI: 1.14, 22.07), a family history of liver disease (AOR 6.37, 95% CI: 1.32, 30.74), a HBsAg seropositive mothers, (AOR 11.19, (95% CI: 3.15, 39.67), and had no vaccination history for HBV (AOR, 6.37, 95% CI: 1.32, 30.74). Children from families with low monthly income, who were home delivered, unvaccinated for HBV or with HBsAg seropositive mother had increased risk of having anti-HBc., Conclusions: The study findings showed an intermediate endemicity of HBV infection in the study setting. The observed rate of residual HBV infection with low rate of immunized children after HBV vaccination was high. Hence, introducing birth dose vaccine, safe injection practice and improving immunization coverage during pregnancy as part of the antenatal care package should be considered. Furthermore, governmental and non-governmental organizations should give attention on timely measures for the prevention of ongoing vertical transmission from mother to child as well as early horizontal transmission of HBV in Hawassa City, Ethiopia.

Mucosal administration of vaccine can produce a strong immune response. Antigens adhere to "M-cells", present at the intestinal mucosa and the M-cells produce immunity after actively transporting luminal antigens to the underlying immune cells. The objective of the present study was to prepare and characterize alginate coated chitosan nanoparticles (ACNPs) loaded with HBsAg as an antigen to produce immunity; additionally anchored with lipopolysaccharide (LPS) as an adjuvant. Ionic gelation method was used to prepare chitosan nanoparticles (CNPs) which were loaded with HBsAg and stabilized by alginate coating to protect from gastric environment. Results showed that the prepared LPS-HB-ACNPs were small and spherical with mean particle size 605.23 nm, polydispersity index 0.234 and Zeta potential -26.2 mV and could effectively protect antigen at GIT in acidic medium. HB-ANCPs were stable during storage at 4 ± 1 and 27 ± 2 °C. Anchoring with LPS showed increased immunity as compared to other formulations. Additionally, NPs elicited significant sIgA at mucosal secretions and IgG antibodies in systemic circulation. Thus, the prepared LPS anchored alginate coated chitosan NPs may be a promising approach as a vaccine delivery system for oral mucosal immunization., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Hepatitis B causes more than 800 000 deaths globally each year. Perinatal infections are a major driver of this burden but can be prevented by vaccination within 24 h of birth. Currently, only 44% of newborn babies in low-income and middle-income countries (LMICs) receive a timely birth dose. We investigated the effects and cost-effectiveness of implementing ambient storage of hepatitis B vaccines under a controlled temperature chain (CTC) protocol and the use of compact prefilled auto-disable (CPAD) devices for community births., Methods: In this mathematical modelling study of perinatal hepatitis B transmission and disease progression, we estimated the coverage impact and cost-effectiveness of implementing CTC and CPAD interventions in the six Global Burden of Disease (GBD) regions containing LMICs. Combinations of four different scenarios of birth dose delivery strategies (cold chain, CTC) and interventions (needle and syringe, CPAD) were modelled across facility or community birth locations. We also estimated the minimum cost and most cost-effective strategy to achieve the WHO 90% hepatitis B birth dose coverage target in GBD regions and in 46 LMICs with a reported coverage of less than 90%., Findings: Current delivery protocols achieved a maximum coverage of 65% (IQR 64-65) across GBD regions. Reaching 90% hepatitis B birth dose coverage across all GBD regions was estimated to cost a minimum of US$687·5 million per annum ($494·0 million more than the estimated current expenditure), of which $516·5 million (75%) was required for CTC and CPAD interventions. Reaching 90% coverage in this way was estimated to be cost saving in five of the six regions (and in 40 of 46 LMICs individually assessed) due to the disease costs averted, with the cost per disability-adjusted life-years averted being less than $83·27 otherwise., Interpretation: Hepatitis B birth dose coverage of 90% is unlikely to be reached under current protocols. CTC and CPAD vaccine strategies present cost-effective solutions to overcome coverage barriers., Funding: The Burnet Institute., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Hepatitis B (HepB) is one of the most common infectious diseases affecting over two billion people worldwide. About one third of all HepB cases are in China. In recent years, China made significant efforts to implement a nationwide HepB vaccination program and reduced the number of unvaccinated infants from 30 to 10%. However, many individuals still remain unprotected, particularly those born before 2003. Consequently, a catch-up retroactive vaccination is an important and potentially cost-effective way to reduce HepB prevalence. In this paper, we analyze a game theoretical model of HepB dynamics that incorporates government-provided vaccination at birth coupled with voluntary retroactive vaccinations. Given the uncertainty about the long-term efficacy of the HepB vaccinations, we study several scenarios. When the waning rate is relatively high, we show that this retroactive vaccination should be a necessary component of any HepB eradication effort. When the vaccine offers long-lasting protection, the voluntary retroactive vaccination brings the disease incidence to sufficiently low levels. Also, we find that the optimal vaccination rates are almost independent of the vaccination coverage at birth. Moreover, it is in an individual's self-interest to vaccinate (and potentially re-vaccinate) at a rate just slightly above the vaccine waning rate.

Background: hepatitis B virus (HBV) and C virus (HCV) are among the leading causes of mortality worldwide. Health care personnel (HCP) are subjected to increased risk of these infections. Therefore, HBV vaccination and post-vaccination serologic testing (PVST) are recommended for them. Our objectives in this study were investigate how well the vaccination guidelines for hospital HCP s were implemented. Moreover, the prevalence rates of HBV and HCV infections were calculated. To determine the presence of immunological memory, vaccinated personnel negative to antibody against HB surface antigen with one dose of HB vaccine were boosted., Methods: From 1 July to 30 November 2017, a cross-sectional study among HCPs working in public hospitals were conducted. All HCPs from various professional categories potentially at risk of exposure to contaminated sources were included. The information was gathered via interview and self-administered questionnaire. The questions were focused on the demographic characteristics, HB vaccination and immunity status and time elapsed since initial vaccination series, and frequency of needelstick injuries during the past 12 months of their work. Moreover, the prevalence rate of HBV and HCV infections were calculated. To determine the presence of immunological memory, subjects negative to HBV seromarkers received a booster dose of the vaccine., Results: A total of 186 out of 766 participants were male and nurses comprised 71% of personnel. Although all HCP were vaccinated, 84% of them completed the course and less than 5% of them received PVST. According to the results, 0.78, 4.6, and 83% were serologically positive to HBV surface antigen, antibodies against HBV core, and S antigens, respectively. Approximately, 91% of seronegative participants responded to a booster dose and only 0.91% of the personnel was anti-HCV positive., Conclusion: Most HCP received full HBV vaccination course. Although a minority did PVST, the HBV vaccine-induced long-term protection and HB vaccine booster were not required. Therefore, policies should be made to increase the rate PVST after immunization. According to the results, the HCV infection rate was low and thus pre-recruitment screening was not necessary.

Introduction: Hepatitis B vaccination of newborns (HBV) and surveillance of pregnant women during antenatal care are complementary to prevent mother to child transmission (MTCT) of HBV infection., Aim: The aim was to identify the prevalence and pattern of HBV infection in pregnant women born before and after implementing HBV vaccination of newborn in Egypt., Methods: The study included 600 women attended antenatal clinic of the Suez Canal University Hospital, Ismailia, Egypt. All were inquired about risk factors of HBV infection, vaccination, and screened for hepatitis markers. HBsAg carriers were tested for HBeAg, HBeAb, ALT, and HBV DNA. Participants were divided into group 1 of 285 (47.5%) vaccinated women ≤ 25 years, and 315 (52.5%) non-vaccinated > 25 years., Results: The prevalence of HBcAg, HBsAg, and HBsAb were 18.3%, 5.0%, and 30.7%. Of the 110 women exposed to infection, 40 (36.4%) cleared infection, 30 (27.2%) were HBsAg carriers, and 40 (36.4%) showed isolated HBcAb. HBsAg carriers were HBeAg negative, HBeAb positive, and HBV-DNA positive and had high ALT. Group 1 had significantly higher frequency of vaccination-related immunity, lower frequency of isolated HBcAb, and susceptibles than group 2 (44.9%, 3.5%, and 38.6% vs. 4.1%, 9.5%, and 75.9% ). The prevalence of HBV exposure and chronic HBsAb carriers in both groups were close (4.9% and 16.5% for group 1 vs. 5.1% and 20% for group 2, p > 0.05)., Conclusion: Although the outcomes of HBV infection were favorable in vaccinated group, chronic HBV represents a potential risk for MTCT that necessitates screening during pregnancy in all public health care settings.

Objective: This article analyzes the effectiveness of a super-accelerated immunization schedule against hepatitis B in patients who have received a liver transplantation., Methods: This is a quantitative and retrospective study based on secondary data of medical records from 177 patients who have received a liver transplantation at the Hospital de Base in São José do Rio Preto, São Paulo State, Brazil, between 1998 and 2016., Results: From the total number of participants, 72.89% were male, 39.55% had a cirrhosis diagnosis with associated causes, 23.16% had hepatocellular carcinoma, 53.11% were classified according to Child-Turcotte-Pugh C score, 58.76% had the hepatitis C virus, 97.18% had received an unconventional immunization schedule, and seroconversion was 36.63% among those with an unconventional schedule. The fact that the patient had the hepatitis C virus was statistically significant considering the lack of protection of the vaccine against the hepatitis B virus; their chances were 5 times higher of not seroconverting at the end of the immunization schedule., Conclusion: The need for high immediate protection in a short term may justify using unconventional immunization schedules in patients who make it to the transplantation waiting list without any previous immunization., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We describe 2 preterm neonates with transient hepatitis B surface (HBs) antigenemia detected after Hepatitis B vaccination. Repeat serology in both cases tested negative for hepatitis B surface antigen, confirming transient HBs antigenemia. The duration of transient HBs antigenemia affirms current literature in the pediatric population.

Background: Hepatitis B virus (HBV) persistently infected about 250 million people worldwide, and a curative treatment remains an unmet medical need. Among many approaches to treat chronic hepatitis B (CHB), therapeutic vaccines have been developed for two decades, but none have yielded promising results in clinical trials. Therefore, dissection of HBV clearance mechanisms during therapeutic vaccination in appropriate models, which could give rise to new curative therapies, is urgently needed. Growing evidence indicates that prolonged and intensive exposure of antigen-specific T cells to viral antigens is a major cause of T cell exhaustion, and decreases anti-HBV immunity efficacy of therapeutic vaccination. HBV X protein (HBx) is expressed at low levels, and the understanding of its immunogenicity and potential in therapeutic CHB vaccines is limited., Methods: HBV genome sequences from CHB patients were cloned into a pAAV plasmid backbone and transfected into immunocompetent mouse hepatocytes through hydrodynamic injection. Mice carrying > 500 IU/mL serum HBV surface antigen (HBs) for more than 4 weeks were considered HBV carriers mimicking human CHB and received 3 doses of weekly HBx vaccine by subcutaneous immunization. Serum HBV clearance was evaluated by monitoring serum HBs and HBV-DNA titers. Residual HBV in the liver was evaluated by western blotting for HBV core antigen. The splenic antigen-specific T cell response was quantified by a 15-mer overlapping peptide-stimulated interferon-γ enzyme-linked immunospot assay. Blood and hepatic immune cells were quantified by flow cytometric analysis., Results: Our HBx-based vaccine induced systemic HBx-specific CD4 + and CD8 + T cell responses in HBV carrier mice and demonstrated significant HBs and HBV-DNA elimination. The protective effect persisted for at least 30 days without additional booster immunization. Different infiltrating myeloid cell subsets, each with distinctive roles during immune-mediated HBV clearance, were found in the liver of vaccinated mice. During vaccine therapy, inflammatory monocyte depletion resulted in sustained HBV clearance inhibition, whereas phagocytic monocyte-derived macrophage and Kupffer cell elimination resulted in only transient inhibition of vaccine-induced HBV clearance., Conclusions: We report the potential role of HBx as a major immunogen in an HBV therapeutic vaccine and the significance of a liver-infiltrating monocyte subset during hepatic viral clearance.

Introduction: The prevalence of co-infection of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is high and increases risk of hepatitis B chronicity and mortality. Despite guidelines for HIV-infected patients to be immunized against HBV, the immunogenicity of the HBV vaccination in HIV-infected patients is lower than that in the HIV-seronegative population., Method: In this study, we performed a systematic review of the literature and meta-analysis of randomized clinical trials to investigate the response rate to an increased dose of HBV vaccination in HIV-infected patients. A fixed-effects model, with heterogeneity and sensitivity analyses, was used. We identified nine studies involving 970 HIV-positive vaccine recipients., Results: The study results were divided into two groups, depending on the time when antibody against hepatitis surface antigen was measured. Results showed a significant increase in response rates among patients who received a double dose of the vaccine versus the standard dose in both subgroups; the pooled odds ratio (OR) was 1.76 (95% confidence interval [CI]: 1.36-2.29) and 2.28 (95% CI: 1.73-3.01) for the rate that was measured 4-6 weeks and >12 months after completion of vaccination, respectively. The total OR was 1.99 (95% CI: 1.64-2.41). No heterogeneity was found., Discussion: Our meta-analysis shows that a double dose of the HBV vaccine may significantly improve the immune response in HIV-infected patients. Higher immunogenicity was observed, when it was measured 4-6 weeks and >12 months after completion of the vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: HBV (hepatitis B virus) vaccination in first year of life is recommended to prevent infection. Observational studies have suggested that vaccination at birth provides protection for 90% of the population for 30 years. Data on response to booster doses and long-term protection are lacking. Methods: We compared HBV antibody levels of healthcare students who were immunized for HBV with a primary series during their first year of life (primary) to students who were immunized with a primary series and received an additional dose at age 18 (boosted) four years earlier. Antibody titres ≥10 mIU/mL were considered adequate. Those that were inadequate received another dose and were reassessed. Results: We assessed 381 students, 80.1% were primary and 19.9% boosted. A significantly higher percentage of students in the boosted group had antibody titre levels ≥10 mIU/mL compared to primary group (88.1% vs. 41.3%, p  < .001). Of 179 students in the primary group with inadequate antibody levels, 134 received a booster dose and 126 of them (94%) developed anti-HBs levels ≥10 mIU/mL. Of 9 students with inadequate levels in the boosted group, 8 received another booster dose and all developed adequate levels. Conclusions: Primary vaccination against HBV at birth does not necessarily provide lifelong adequate antibody levels. Boosting at 18 years reinforces antibody levels for at least four more years. Current guidelines recommend testing and boosting all medical personal. Based on our study, it may be prudent to extend this practice to all individuals who are at higher risk.

Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1 + dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1 + macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.

Introduction: The benefits of vaccine co-administration include improved vaccine acceptance and uptake resulting in an increased coverage and protection against multiple childhood diseases, with minimal medical visits. The diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis- Haemophilus influenzae type b vaccine (DTaP-HBV-IPV/Hib) has been available for more than 19 years and is recommended for co-administration with several other infant vaccines., Areas Covered: This is a comprehensive review (34 studies, 21,000 participants) describing the immunogenicity and safety of DTaP-HBV-IPV/Hib when co-administered with 12 different vaccines in infants including pneumococcal, meningococcal, rotavirus or measles-mumps-rubella-varicella., Expert Opinion: Interactions among co-administered vaccines are complex. Therefore, co-administration data are critical before a vaccination regimen can be recommended. Co-administration of DTaP-HBV-IPV/Hib with other routinely administered vaccines was associated with high percentages of children achieving seroprotection/vaccine response against DTaP-HBV-IPV/Hib antigens. In addition, co-administration was not associated with clinically significant interference in immune responses to co-administered vaccines and was well tolerated. Increased systemic reactions observed with some combinations (DTaP-HBV-IPV/Hib + pneumococcal conjugate or meningococcal serogroup B vaccines) were mitigated by prophylactic paracetamol administration. The data reported here, which represent the most frequently used co-administrations of DTaP-HBV-IPV/Hib worldwide, support the concomitant administration of DTaP-HBV-IPV/Hib with other routinely recommended infant vaccines.

Background: There are 43 000 new cases of hepatitis B virus infection and 1000 cases of perinatally acquired infection each year in the United States. National recommendations are to administer hepatitis B (HepB) vaccine to all stable newborns >2000 g within 24 hours of birth. Our primary objective was to increase institutional vaccination rates from a baseline of 52% to goal >85% before hospital discharge., Methods: In February 2017, we instituted a multidisciplinary quality improvement project aimed at increasing HepB vaccination birth dose rates. Interventions included (1) standardizing the process of offering HepB vaccine via scripting and timing, (2) engaging and educating parents, and (3) educating physicians and nurses regarding the importance of HepB vaccination and strategies to discuss HepB vaccination with vaccine-hesitant parents. The main outcome measure was the percentage of newborns receiving HepB vaccination by discharge. The secondary outcome was the percentage of newborns receiving HepB vaccination by 12 hours of life per New York State Department of Health recommendation. Data were analyzed by using statistical process control P-charts., Results: A total of 21 108 newborns were included between July 2015 and April 2019. In addition to several upward centerline shifts, implementation of interventions resulted in increased and sustained HepB vaccination rates by hospital discharge from a baseline of 52.4% to 72.5%. Rates by 12 hours of life increased from 21.5% to 42.5%., Conclusions: Multidisciplinary collaboration, scripting, and provider and staff education regarding the risks of hepatitis B virus, benefits of HepB vaccine, and strategies to discuss HepB vaccination with parents significantly increased vaccination rates. Further efforts to improve vaccination rates to within 12 hours are preferable., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background & Aims: Hepatitis B virus (HBV) infection persists because the virus-specific immune response is dysfunctional. Therapeutic vaccines might be used to end immune tolerance to the virus in patients with chronic infection, but these have not been effective in patients so far. In patients with chronic HBV infection, high levels of virus antigens might prevent induction of HBV-specific immune responses. We investigated whether knocking down expression levels of HBV antigens in liver might increase the efficacy of HBV vaccines in mice., Methods: We performed studies with male C57BL/6 mice that persistently replicate HBV (genotype D, serotype ayw)-either from a transgene or after infection with an adeno-associated virus that transferred an overlength HBV genome-and expressed HB surface antigen at levels relevant to patients. Small hairpin or small interfering (si)RNAs against the common 3'-end of all HBV transcripts were used to knock down antigen expression in mouse hepatocytes. siRNAs were chemically stabilized and conjugated to N-acetylgalactosamine to increase liver uptake. Control mice were given either entecavir or non-HBV-specific siRNAs and vaccine components. Eight to 12 weeks later, mice were immunized twice with a mixture of adjuvanted HBV S and core antigen, followed by a modified Vaccinia virus Ankara vector to induce HBV-specific B- and T-cell responses. Serum and liver samples were collected and analyzed for HBV-specific immune responses, liver damage, and viral parameters., Results: In both models of HBV infection, mice that express hepatocyte-specific small hairpin RNAs or that were given subcutaneous injections of siRNAs had reduced levels of HBV antigens, HBV replication, and viremia (1-3 log 10 reduction) compared to mice given control RNAs. Vaccination induced production of HBV-neutralizing antibodies and increased numbers and functionality of HBV-specific, CD8 + T cells in mice with low, but not in mice with high, levels of HBV antigen. Mice with initially high titers of HBV and knockdown of HBV antigen expression, but not mice with reduced viremia after administration of entecavir, developed polyfunctional, HBV-specific CD8 + T cells, and HBV was eliminated., Conclusions: In mice with high levels of HBV replication, knockdown of HBV antigen expression along with a therapeutic vaccination strategy, but not knockdown alone, increased numbers of effector T cells and eliminated the virus. These findings indicate that high titers of virus antigens reduce the efficacy of therapeutic vaccination. Anti-HBV siRNAs and therapeutic vaccines are each being tested in clinical trials-their combination might cure chronic HBV infection., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination., Materials and Methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests., Results: The prevalence rates of HBsAg, anti-HBc total, anti- HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001)., Conclusions: These findings show the elimination of HBVmcarriers in children <11 years, eight years following introduction of the vaccination against HBV., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Background: Chronic hepatitis B (CHB) is endemic in the Aboriginal population of Australia's Northern Territory (NT). However, many people's hepatitis B virus (HBV) status remains unknown., Objective: 1. To maximise the utility of existing HBV test and vaccination data in the NT by creating a linked dataset and computerised algorithmic coding. 2. To undertake rigorous quality assurance processes to establish feasibility of using the linked dataset and computerised algorithmic coding for individual care for people living with CHB., Methods: Step 1: We used deterministic data linkage to merge information from three separate patient databases. HBV testing and vaccination data from 2008-2016 was linked and extracted for 19,314 people from 21 remote Aboriginal communities in the Top End of the NT. Step 2: A computerised algorithm was developed to allocate one of ten HBV codes to each individual. Step 3: A quality assurance process was undertaken by a clinician, using standardised processes, manually reviewing all three databases, for a subset of 5,293 Aboriginal people from five communities to check the accuracy of each allocated code., Results: The process of data linking individuals was highly accurate at 99.9%. The quality assurance process detected an overall error rate of 17.7% on the HBV code generated by the computerised algorithm. Errors occurred in source documentation, primarily from the historical upload of paper-based records to electronic health records. An overall HBV prevalence of 2.6% in five communities was found, which included ten cases of CHB who were previously unaware of infection and not engaged in care., Conclusions: Data linkage of individuals was highly accurate. Data quality issues and poor sensitivity in the codes produced by the computerised algorithm were uncovered in the quality assurance process. By systematically, manually reviewing all available data we were able to allocate a HBV status to 91% of the study population., Competing Interests: The authors have declared that no competing interests exist.

Background: International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV)., Methods and Findings: We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995-2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R2 = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%-37%) and 62% at 50 years (95% CI 57%-68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission., Conclusions: The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level., Competing Interests: The authors have declared that no competing interests exist.

This study examines different factors influencing the 13-valent pneumococcal conjugate vaccine (PCV13) specific antibody response in 8-13 months old Danish children starting in day care. We present secondary findings to the ProbiComp study, which included nose swabs, buccal swabs and blood samples from the children before entering day care (baseline) and again after 6 months. Pneumococci isolated from nose swabs were identified by latex agglutination kit and Quellung reaction. Luminex-based assay was used for antibody measurements against specific anti-pneumococcal capsular IgG. Buccal gene expression was analyzed by qPCR. Statistical analyses were performed in R and included Pearson's Chi-squared test, Welch two sample t-test and linear regression models. The PCV13 antibody response was unaffected by whether the children were carriers or non-carriers of any pneumococcal serotype. Having siblings increased the risk of carrying serotype 21 before day care (p = 0.020), and having siblings increased the PCV13 antibody response at the end of study (p = 0.0135). Hepatitis B-vaccination increased the PCV13 antibody response before day care attendance (p = 0.005). The expression of IL8 and IL1B was higher in children carrying any pneumococcal serotype at baseline compared to non-carriers (p = 0.0125 and p = 0.0268 respectively).

Background: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy., Methods: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26)., Results: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme., Conclusions: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.

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.

Background: This study aims at evaluating the benefits and harms of hepatitis B immune globulin (HBIG) and hepatitis B vaccine (HBVac) in preventing mother to child transmission in HBV surface antigen (HBsAg) positive pregnant women during antenatal period., Methods: Seven electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Database, Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), and 3 clinical trial registry platforms were searched from inception date to December 2017. Only randomized controlled trials (RCTs) were included in this study. The Cochrane risk of bias tool was applied to assessing the risk of bias. The outcomes were analyzed by Review Manager 5.3 software., Results: Sixteen RCTs involving 2440 HBsAg positive pregnant women were included in the meta-analysis. Compared with placebo group, HBIG and HBVac group had a significant decrease in the number of newborns who were HBsAg positive (relative risks [RR]: 0.2, 95% confidence interval [CI] [0.18, 0.40], P < .00001) and HBV-DNA positive (RR: 0.25, 95% CI [0.09, 0.71], P = .010), and had a significant increase in the number of anti-HBs positive newborns (RR: 3.95, 95% CI [3.11, 5.00], P < .00001). After 1-year follow up, the number of HBsAg positive newborns continued to decline (RR: 0.09, 95% CI [0.04, 0.20], P < .00001) and the number of anti-HBs positive newborns continued to increase in HBIG and HBVac group (RR: 1.30, 95% CI [1.22, 1.38], P < .00001). Compared with HBIG group, HBIG and HBVac group had no significant difference in the number of HBsAg positive newborns (RR: 1.68, 95% CI [0.66, 4.30], P = .28), and had a significant decrease in the number of HBsAg positive newborns (RR: 0.31, 95% CI [0.12, 0.84], P = .02). Additionally, only 1 study reported 2 swelling cases, 4 studies were reported no adverse events, and 11 studies were not report adverse reaction., Conclusions: HBIG and HBVac could be an effective alternative for HBsAg positive pregnant women to prevent mother to child transmission. However, due to the limitations of the study, the long-term efficacy and safety of HBIG and HBVac still need long-term and high-quality research to confirm.

Objectives: Hepatitis B is endemic in Lao PDR with 8-10% of the adult population being chronically infected. We investigated the impact of hepatitis B vaccination on infection in adolescents born shortly before and after the introduction of the vaccine in 2001., Methods: 779 students from Vientiane Capital and Bolikhamxay province were tested for HBV markers by ELISA. Socio-demographic information was collected with a standardized questionnaire. Predictors/risk factors for seroprotection or exposure to hepatitis B infection were assessed by bivariate and multivariable analyses., Results: The prevalence of a serological vaccination profile increased significantly after the introduction of the vaccine (13.2%-21.9%, p < 0.05, in Vientiane; 3.0%-19.7%, p < 0.001, in Bolikhamxay), which translated into at least a 2-times lower prevalence of past infection. In logistic regression, older students in Bolikhamxay were less likely to be vaccinated and more likely to have been infected by HBV in the past., Conclusion: Even though this study documented a sizable and lasting reduction in past hepatitis B infections in adolescents born after the introduction of infant hepatitis B vaccination, the overall levels of protective anti-HBs were low and warrant at least the introduction of a booster for adolescents. Furthermore, we suggest improving the coverage of the hepatitis B birth dose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2-32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters., Methods: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs., Results: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.8 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups., Conclusions: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI ≥ 25 and prebooster anti-HBs concentration <2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A failure of neurodevelopmental differentiation at the level of oligodendroglial-astrocytic biprogenitors (O2A) is shown to be involved in the pathogenesis of both multiple sclerosis (MS) and glioblastoma multiforme (GBM). In this review article, we suggest that certain antigens of Hepatitis B Virus (HBV) and HBV-Vaccine (HBV-V) could act as immune stimulants in GBM treatment based on several lines of evidence. HBV-Vs may cause rare but prominent neuroimmune side effects including demyelination and multiple sclerosis, which may be associated with HBV-proteins creating antigenic mimicry of oligodendroglial progenitors. The combined prevalance of HBV and Hepatitis C Virus-carrier state is less in patients with brain tumors compared to healthy subjects. Furthermore, within the population of patients with brain tumors, the prevalence is even about two times lesser in GBM in comparison to those with a diagnosis of meningioma. Although indirectly, this epidemiological data may indicate that the immune response triggered against hepadnavirus antigens would eliminate aberrantly differentiating O2A progenitor cells giving rise to GBMs. Moreover, Hepatitis B surface antigen-antibody variable domain is among the top 100 differentially expressed transcripts in fresh frozen and formalin-fixed paraffin-embeded specimens obtained from pediatric GBM tissues in comparison to the control brain tissues. However, the provided evidence is still premature and we think that HBV-V warrants investigation first by epidemiological studies and then by animal experiments to determine whether it reduces the risk of GBM and whether it could slow GBM growth via immune stimulation., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Laboratory staff handling blood or biological samples are at risk for accidental injury or exposure to blood-borne pathogens. Hepatitis B virus (HBV) vaccinations for laboratory staff can minimize these risks., Objective: The aims of this study were to determine the prevalence of occupational exposure to needle stick injuries (NSIs) and assess HBV vaccination coverage among clinical laboratory staff in Sana'a, Yemen., Methods: A cross-sectional survey was conducted among clinical laboratory staff who were involved in handling and processing laboratory samples at the main public and private clinical laboratories in Sana'a. Data collection was done using a semistructured questionnaire. The questionnaire was divided into 3 parts. Part 1 included information on sociodemographic characteristics of participants. Part 2 included information on the availability of the personal protective equipment in the laboratories, such as lab coats and gloves. Part 3 included questions about the history of injury during work in the laboratory and the vaccination status for HBV., Results: A total of 219/362 (60%) participants had been accidentally injured while working in the laboratory. Of those, 14.6% (32/219) had been injured during the last 3 months preceding the data collection. Receiving the biosafety manual was significantly associated with lower risk of injury. Out of those who were injured, 54.8% (120/219) had received first aid. About three-quarters of respondents reported that they had been vaccinated against HBV. The vaccination against HBV was significantly higher among laboratory staff who were working at private laboratories (P=.01), who had postgraduate degrees (P=.005), and who received the biosafety manual (P=.03)., Conclusions: Occupational exposure to NSI is still a major problem among laboratory staff in public and private laboratories in Sana'a, Yemen. The high incidence of injuries among laboratory staff and the low rate of receiving first aid in laboratories combined with low vaccination coverage indicates that all laboratory staff are at risk of exposure to HBV. Therefore, strengthening supervision, legalizing HBV vaccinations for all laboratory staff, and optimizing laboratory practices regarding the management of sharps can minimize risks and prerequisites in Yemen., (©Nabil Saleh Al-Abhar, Ghuzlan Saeed Moghram, Eshrak Abdulmalek Al-Gunaid, Abdulwahed Al Serouri, Yousef Khader. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 31.03.2020.)

There are currently about 257 million people suffering from chronic HBV infection worldwide. In many cases, an insufficient Tcell response is causative for establishment of a chronic infection. To ensure a robust cellular immune response and induction of neutralizing antibodies a novel vaccine platform based on modified cell-permeable HBV capsids was utilized. Cell permeability was achieved by fusion of the membrane-permeable TLM-peptide to HBV core monomers, assembling the capsids. Insertion of a Strep-tagIII into the spike tip domain that protrudes from the capsid surface enables flexible loading with antigens that are fused to streptavidin. In this study, HBV surface antigen-derived PreS1PreS2 domain, fused to monomeric streptavidin, served as cargo antigen. Binding between antigen and capsids was characterized by surface plasmon resonance spectroscopy, electron microscopy and density gradient centrifugation. Confocal immunofluorescence microscopy and in vivo imaging of immunized mice demonstrated membrane permeability of cargo-loaded carriers and spread of antigen over the whole organism. Immunization experiments of mice revealed a robust induction of a specific cellular immune response, leading to destruction of HBV-positive cells and induction of HBV-specific neutralizing antibodies. Membrane permeability of these carriers allows needle-free application of antigen-loaded capsids as evidenced by induction of an HBV-specific CTL response and HBV-specific B cell response after oral or transdermal vaccination. These data indicate that cell-permeable antigen carriers, based on HBV capsids and loaded with HBV antigen, have the capacity to induce a cellular and a neutralizing humoral immune response. In addition, cell permeability of the vaccine platform enables antigen transfer across several cell layers, that could allow oral or transdermal immunization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Universal vaccination is the most effective strategy to control hepatitis B virus (HBV) infection. In Argentina, vaccination against HBV was incorporated in year 2000 for newborns and in 2003 for 11 years old children. However, there is a paucity of data about protection levels against HBV infection. The aim of this work was to determine the prevalence of seroprotective anti-HBs antibodies (aHBs) in Argentina. Serum samples negative for HBsAg and anti-HBc from 132 children born after year 2000 and 762 blood donors, older than 18 years, from five centers across the country, were analyzed for aHBs. Titers ≥10 mIU/mL were observed in 74/132 children (56.1%) and 336/762 (44.1%) in blood donors. The median age for blood donors was 33.9 (23-43); from them, 210 (27.6%) were born after 1992 and, therefore, were catch-up by vaccine implementation at 11 years old age. Donors born in 1992 or before showed a significantly lower frequency of protection (32.2%) compared to donors born after 1992 (75.2%), p < 0.0001. In addition, significant differences were observed in the status of seroprotection between different participating centers (p = 0.024). Implementation of HBV vaccine in 2000 and 2003 implied an overall increase of the aHBs seroprotective rates, with a particularly adequate response in children vaccinated at 11 years old age. The observed results suggest that population born in 1992 or before is currently the most susceptible. Consequently, it would be advisable to become aware of the risk of transmission in this age group and to stress this population vaccination campaigns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The risk of transmission of bloodborne pathogens, including hepatitis B virus (HBV) to healthcare workers (HCWs) is well known. In 2005 we performed a survey on HBV prevention in HCWs in the European Union (EU). An update of the 2005 survey deemed necessary as an EU Council Directive (2010/32/EU) on sharps injuries was to be implemented into national legislation by 11 May 2013 and more countries were starting universal HBV vaccination., Methods: We performed an electronic survey in 2016, among national representatives from the Occupational Medicine section of the European Union of Medical Specialists (UEMS), to find out how policies have been put into practice in the European Union countries (plus Norway and Switzerland). The data were updated in 2019., Results: Answers were received from 21 countries (among them 19 EU Member States), representing 78% of the population and 60% of HCWs in the EU-28. HBV vaccination was mandatory for medical and nursing staff in 10 countries; for other paramedical staff, medical and nursing students in 9 countries; for paramedical students in 8 countries; for cleaning staff in 7 countries; and for technical staff in 5 countries; it was recommended in all but one of other countries. Serotesting before vaccination was done in 7 countries. The vaccination schedule most often used was 0, 1, 6 months (18countries), monovalent HBV vaccine was used in 14 countries, and combined (HAV + HBV) vaccine in 11 countries. Serotesting after vaccination was done in 18 countries and boosters were recommended in 14 countries. A non-responder policy was present in 18 countries. HBV vaccination coverage (5 countries) was 70-95%. Sharps injuries were reported in 13 countries, nationwide in 7 of them; European-wide reporting was not mentioned by respondents., Discussion: These results show the variation in the implementation of EU legislation in the participating countries. More consultation between actors at EU level, including enhancing medical surveillance in occupational medicine could help to optimise policies in European countries in order to further reduce HBV transmission to HCWs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hepatitis B is a severe public health problem. The main world health centers have discussed it due to its pandemic proportion, high pathogenicity and infectivity. This study aimed to determine the immunization profile of dental surgeons - against hepatitis B virus (HBV) in the Public Health System (PHS) through the detection of anti-HBsAg antibodies by immunochromatography and associations with dental surgeons' social and educational profile, factors related to professional knowledge and practices. This is a cross-sectional study on the prevalence of vaccination and immune status to HBV in dentists of Sao Paulo State PHS. Data collection occurred in three stages: questionnaire application, analysis of adhesion to the vaccination protocol and anti-HBsAg tests. Statistical analysis used the Bivariate Analysis and the Binary Logistic Regression. From the total of 219 interviewees, 74.9% reported having received three doses of the vaccine, but 35.6% were not immune to HBV. The dependent variable was associated with years in the public service (years) (OR [Odds Ratio]=1.04; 95% CI 1.00-1.08); knowledge on the subject (OR=6.93; 95% CI 1.39-34.40); incorrect answer concerning the etiological agent of the disease (OR=2.60; 95% CI 1.30-5.22); ignorance on the number of vaccine doses that have been administered (OR=3.43; 95% CI 1.14-10.30); and less than three doses of the vaccine in the immunization schedule (OR=8.76; 95% CI 3.50-21.91). A considerable portion of professionals non-immune to the HBV were found. We concluded that knowledge, years of practice and completion of the vaccination schedule (three doses) affected dental surgeons' immune status to HBV.

Background : The rs368234815 polymorphism of interferon-λ4 (IFN-λ4) gene ( IFNL4 ) is involved in HBV surface antigen (HBsAg) clearance in non-uremic subjects. The rs368234815 ΔG/ΔG genotype can express IFN-λ4 while the TT/TT genotype cannot. We investigated whether rs368234815 is associated with the development of HBsAg antibodies (anti-HBs) in response to vaccination or infection, and HBsAg loss after infection in uremic patients on extracorporeal dialysis. Research design and methods : Dialyzed patients (n = 467) were genotyped for rs368234815 by the polymerase chain reaction-restriction fragment length polymorphism method. Non-responders to HBV vaccination we compared with responders. HBsAg positive patients not able to develop anti-HBs we compared with individuals who eliminated HBsAg and generated anti-HBs. HBsAg positive patients we compared with subjects who eliminated HBsAg. Results : The ∆G allele was associated with the 1.6-fold higher risk not to develop anti-HBs titers ≥10 IU/L in response to HBV vaccination and infection (P = 0.016 adjusted for gender, age at dialysis onset, HCV RNA). The ∆G/∆G genotype indicated a higher probability of non-responsiveness to HBV vaccination than the TT/TT genotype (OR 2.64, 95%CI 1.01-6.87, adjusted P = 0.048). Conclusions : In extracorporeal dialysis patients, IFNL4 rs368234815 is associated with the capacity to produce protective anti-HBs titers in response to HBV vaccination.

Children with acute lymphocytic leukemia (ALL) are at an increased risk of acquiring hepatitis B infection due to repeated exposure to blood products. They have poor response to vaccination due to immunosuppressive effects of malignant disease and chemotherapy; hence necessitating vaccination with increased doses or increased amount of vaccine or both. The authors studied 44 patients (32 boys and 12 girls) given double dose hepatitis B vaccination at 0, 1 and 2 mo during induction and consolidation phase of therapy. Of the thirty patients who completed the study, only 13 (43.34%) developed protective antibody levels (titres >10 mIU/ml) measured 4 wk after the third dose. The authors conclude that with three double dose schedule of Hepatitis B vaccination, response rate is poor. Therefore, for protection from Hepatitis B infection during initial phase of therapy, there is a need to provide passive immunization.

Background and Aims: Hepatitis B virus (HBV) vaccination is recommended to all employees who have an occupational risk in the Netherlands. This study assessed the determinants of the immune response to primary standard three-dose HBV vaccination (0, 1, 6 months), with the main focus on ethnicity., Methods: Out of 76 239 individuals who received HBV vaccination between April 1983 and December 2017, 11 567 persons with a known country of birth and complete vaccination schedule were included in this study. Weighted multiple logistic regression with Firth's bias adjustment was used to assess the determinants of nonresponse (anti-HBs < 10 mIU/mL) and low response (anti-HBs 10-99 mIU/mL)., Results: Baseline characteristics of the study population (n = 11 567) were as follows: mean age 27.5 years (95% confidence interval [CI], 27.23-27.72), 99.4% born in the Netherlands and 93.5% of Western European origin. Of all identified subjects, 180 (1.6%) were HBV vaccine nonresponders and 549 (4.8%) were low responders. When compared with individuals aged <40 years, the rate of nonresponse (4.3% vs 0.8%; P < .001) and low response (11.9% vs 2.9%; P < .001) was higher in those aged 40 years or older. The height of anti-HBs levels were lower in those subjects aged >40 years in comparison with those younger than 40 years, P < .001. All nonresponders were born in the Netherlands. Although no significant association was found between nonresponse and individuals of Western European origin (adjusted odds ratio [aOR] = 1.20; 95% CI, 0.66-2.44; P = .163), low response to HBV vaccination was significantly associated with Western European origin (aOR = 2.21; 95% CI, 1.41-3.86; P = .001). Significant determinants for nonresponse were older age at vaccination (aOR = 1.06; 95% CI, 1.06-1.07; P < .001) and male gender (aOR = 2.51; 95% CI, 1.97-3.22; P < .001)., Conclusions: The nonresponse rate was low in our study population. Our findings suggest that the vaccines being used for the primary vaccination are probably less immunogenic for older individuals, males, and persons of Western European origin., (© 2019 Wiley Periodicals, Inc.)

Analysis of B-cell specificities at the single cell level provides important information on how the B-cell compartment responds when challenged by infection or vaccination. We recently developed a reversed B-cell FluoroSpot assay and showed that it could be used to detect B cells specific for different antigens simultaneously in a mouse model. The aim of this study was to further develop the method to detect and quantify antigen-specific memory B cells (MBCs) in humans where circulating antigen-specific cells are less frequent. We show that MBCs specific for three antigens, tetanus toxoid, hepatitis B surface antigen and cytomegalovirus pp65, could be detected simultaneously in one well. In addition to enumerating antigen-specific MBCs, we also assessed the spot volume to estimate the intensity of the response in individual cells and found this to be a new and sensitive approach to study MBC responses after vaccination. This unique B-cell FluoroSpot approach provides a simple and sensitive multiplex analysis of MBCs and can be adapted to most antigens and host species., Competing Interests: Declaration of Competing Interest Peter Jahnmatz, Bartek Makower and Niklas Ahlborg are employed by Mabtech AB, Sweden. Several of the reagents and one of the FluoroSpot reader systems used in this study are produced by Mabtech., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The prevalence of hepatitis B virus (HBV) infection was an imbalance in different provinces of China. This study aimed to investigate the prevalence of HBV infection and evaluate the prophylactic measures in a public hospital of northeast China over the preceding 13 years. A total of 13,948 patients in 2004 and 15,256 patients in 2017 of Shengjing Hospital of China Medical University were tested of serum HBsAg, HBeAg, HBsAb, HBeAb, and HBcAb levels with Abbott MEIA Kits. In people born before 1992, HBsAg-positive rate was 5.45% and 6.47%; isolated HBsAb positive rate was 14.62% and 21.24%; HBV marker negative rate was 54.27% and 42.77% in 2004 and 2017 survey, respectively. The males had a significant higher HBsAg-positive rate than the females. In people born during 1992-2004, HBsAg positive rate was 0.58% and 0.57%, isolated HBsAb positive rate was 41.47% and 46.57%; and HBV marker negative rate was 51.97% and 46.86% in 2004 and 2017 survey, respectively. Males and females had no difference of HBsAg-positive rate. In children born after 2005, HBsAg positive rate was 0.11%, isolated HBsAb positive rate was 76.68%, and HBV marker negative rate was 18.51% in 2017 survey. No difference of HBsAg-positive rate was found between the genders. A dramatic decrease of HBsAg positive rate and a progressive increase of HBsAb-positive rate were found among people born after 1992 and progressed further in those born after 2005. Immunization of infants and timely birth dose was the key method for prevention of HBV infection. Expanded HB vaccination would be needed for people born before 2005, especially those born between 1992 and 2004.

Hepatitis B surface antigen (HBsAg) loss and/or seroconversion is the ideal endpoint for the treatment of patients with chronic hepatitis B (CHB), whereas the "functional cure" of hepatitis B virus (HBV) infection is hard to obtain with routine therapeutics. Thus, potential new strategies are explored to cure HBV infection. A combination immunomodulatory therapeutic regime was used in a 43-year-old female patient with hepatitis B e antigen (HBeAg)-negative CHB; the regimen included consecutive combination therapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) plus HBV vaccine, in addition to ongoing normal interferon (IFN)- α 2b treatment. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBsAg, and hepatitis B surface antibody (HBsAb) were monitored every 6 months. The ALT level normalized and HBV DNA decreased to a level below the limit of detection within 3 months after the initiation of IFN- α 2b therapy. After an entire year of IFN treatment, serum HBsAg decreased to a very low level (3.16 IU/mL), and HBsAb was still negative (0.78 mIU/mL). Then, rhGM-CSF and the HBV vaccine were applied, in addition to continuous IFN therapy. A steady decline in HBsAg was observed, and HBsAg loss with HBsAb seroconversion was achieved 12 months after initiation of the combination treatment with rhGM-CSF and HBV vaccine; the IFN- α 2b was discontinued for the later 6 months. A therapeutic regimen with GM-CSF plus HBV vaccine could keep the immune system actively stimulated and trigger an HBV-specific immune response to control, or even clear the virus; this regimen may be helpful in the "cure" of HBV infection when combined with IFN- α .

Objectives: To determine the required hepatitis B vaccine doses for subjects who were seronegative for three hepatitis B seromarkers during their youth who wish to have seroprotective antibodies against the hepatitis B surface antigen (anti-HBs)., Methods: We conducted a retrospective cohort study. From 2012 to 2015, graduate school students born after 1986 who were seronegative for three hepatitis B virus seromarkers at college entrance (n = 1037) were recruited. Four groups of subjects received zero to three doses of a hepatitis B vaccine booster at their free willingness, and their anti-HBs titre were measured at their graduate school entrance. Very low and extremely low antibody titres against the hepatitis B surface antigen were elucidated by graphic inference to determine the required booster dose cut-off value for seropositivity after revaccination., Results: The anti-HBs seropositive rates in the four groups of subjects receiving the hepatitis B booster vaccine(s) were 17.7%, 52.1%, 78.6% and 90.9% for those receiving zero, one, two and three doses, respectively. In subjects with very low antibody titres against the hepatitis B surface antigen after one dose of the vaccine booster and subjects with an extremely low titre after two doses of the booster, the seropositive rates reached 95% at the cut-off value of 3 mIU/ml., Conclusion: A seropositive rate of at least 95% can be reached by the administration of two hepatitis B booster doses to youths with extremely low antibody titres against the hepatitis B surface antigen (<3 mIU/ml) and administering one dose to those with very low titres (3-10 mIU/ml) at college., (© The Author(s) 2019. Published by Oxford University Press.)