Envelope Antigen Research Articles

Hepatitis B virus infection and HBeAg positivity among pregnant women in South West Uganda.

BackgroundHepatitis B virus is a public health burden in Uganda, yet little is known about its epidemiology in pregnancy.ObjectiveThis study aimed at determining the prevalence and associated risk factors of hepatitis B virus infection among pregnant women attending antenatal care at the Kyazanga Health Centre IV in Lwengo District, Uganda.MethodsThis cross-sectional study was conducted from April 2021 to June 2021 and analysed qualitative data that were collected using a structured in-person questionnaire. Aseptically collected blood specimens were screened for hepatitis B virus infection using an immunochromatographic rapid diagnostic test kit. Participants who were positive for the hepatitis B surface antigen (HBsAg) were further screened for hepatitis B envelope antigen (HBeAg) using commercial rapid diagnostic test kits.ResultsOut of 384 pregnant women studied, eight tested positive for HBsAg. This gave a prevalence of 2.1% (95% confidence interval: 1.0% – 4.1%); 5/8 (62.5%) were positive for HBeAg. None of the variables studied were significantly associated with HBsAg positivity among pregnant women.ConclusionHepatitis B viral infection is still a public health challenge in pregnant women with possible risk for vertical transmission to their babies in the study area. We recommend routine screening for hepatitis B virus in pregnancy in addition to strengthening current strategies aimed at controlling and preventing hepatitis B infection spread and transmission.

Epidemiology, clinical features, and molecular detection of orf virus in Haryana (India) and its adjoining areas.

Orf is an acute, highly contagious, and economically important viral disease of small ruminants. In this study, six orf suspected outbreaks among goats and sheep were investigated from Haryana state and adjoining areas of Rajasthan state during the year 2021. The disease was diagnosed on the basis of clinical signs and molecular identification. The causative agent of the disease, orf virus (ORFV), was confirmed using polymerase chain reaction (PCR) targeting immunodominant envelope antigen (B2L) gene and confirmed by sequencing. The morbidity in goats ranged from 8.75 to 100%, whereas in sheep, it ranged from 0 to 8%. The higher mortality was observed among flocks with mixed infections of orf and peste des petits (PPR) or orf and haemonchosis as compared to other outbreaks. The phylogenetic analysis of sequenced PCR products clustered the current study strains in the same clad with Indian as well as strains from other countries with nucleotide identity more than 99%, signifying a close genetic relationship. The study highlighted the circulation of strains of a single cluster among sheep and goats in Haryana and adjoining areas. Prompt diagnosis of the disease is highly important for facilitating the implementation of control measures to minimize the losses suffered by small and marginal farmers in this region. Further detailed studies are required to delineate the molecular details of ORFV for better understanding the dynamics and molecular epidemiology of strains circulating in the country and for designing the effective vaccines against the disease which are currently lacking in the country.

MRNA vaccines induce rapid antibody responses in mice

mRNA vaccines can be developed and produced quickly, making them prime candidates for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. Thus, we sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first compared the immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA (4 µg/mouse), but not DNA (50 µg/mouse), immunization. Comparing innate responses hours post immunization, the mRNA vaccine induced increased levels of IL-5, IL-6, and MCP-1 cytokines which maybe promoting humoral responses downstream. We then evaluated the immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines of the same HIV-1 envelope antigen in mice. Again, induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7–14 following DNA, protein, and RhAd52 vaccination. Thus, eliciting rapid humoral immunity may be a unique and advantageous property of mRNA vaccines for controlling infectious disease outbreaks.

Sero-Prevalence, Infectivity, and Associated Risk Factors of Hepatitis B Virus Among Pregnant Women Attending Antenatal Care in Sankura Primary Hospital, Silte Zone, Southern Ethiopia, 2021

Background: Hepatitis B (HBV) infection causes a major public health problem around the globe. Therefore, this study aimed to assess the Seroprevalence, infectivity, and associated factors of hepatitis B virus infection among pregnant women attending antenatal care in Sankura Primary Hospital, Southern Ethiopia. Methods: A cross-sectional study design was conducted in Sankura Primary Hospital, Southern Ethiopia, from April to June 2020. A total of 338 pregnant women were recruited using systematic random sampling. Sociodemographic and associated risk factors were collected through a structured questionnaire. Blood samples and plasma analysis were performed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen (HBeAg) using the rapid test strip method. Statistical analysis was done using SPSS version 20, and P-value < 0.05 was considered statistically significant. Results: The overall Seroprevalence of HBsAg was 11 (3.3%) [95% CI 1.5% - 5.0%], of whom 2 (18.2%) were positive for HBeAg. In multivariate analysis, a history of blood transfusion [AOR=4.8 95% CI (1.25-6.69)] and contact with a family history of the liver [AOR=5.7 95% CI (1.28-7.9)] was found to be significant predictors of HBV infections. Conclusion: The Seroprevalence of HBV infection among pregnant women in the study area was intermediate. Family history of liver disease and blood transfusion were risk factors associated with HBV infection. Hence, improving the screening of blood, increasing awareness about the transmission of HBV infection, and screening pregnant women for HBV infection should be implemented. The government will build efficient service delivery models equipped with an appropriate and well-trained workforce.

Augmenting glycosylation‐directed folding pathways enhances the fidelity of HIV Env immunogen production in plants

Heterologous glycoprotein production relies on host glycosylation‐dependent folding. When the biosynthetic machinery differs from the usual expression host, there is scope to remodel the assembly pathway to enhance glycoprotein production. Here we explore the integration of chaperone coexpression with glyco‐engineering to improve the production of a model HIV‐1 envelope antigen. Calreticulin was coexpressed to support protein folding together with Leishmania major STT3D oligosaccharyltransferase, to improve glycan occupancy, RNA interference to suppress the formation of truncated glycans, and Nicotiana benthamiana plants lacking α1,3‐fucosyltransferase and β1,2‐xylosyltransferase was used as an expression host to prevent plant‐specific complex N‐glycans forming. This approach reduced the formation of undesired aggregates, which predominated in the absence of glyco‐engineering. The resulting antigen also exhibited increased glycan occupancy, albeit to a slightly lower level than the equivalent mammalian cell‐produced protein. The antigen was decorated almost exclusively with oligomannose glycans, which were less processed compared with the mammalian protein. Immunized rabbits developed comparable immune responses to the plant‐produced and mammalian cell‐derived antigens, including the induction of autologous neutralizing antibodies when the proteins were used to boost DNA and modified vaccinia Ankara virus‐vectored vaccines. This study demonstrates that engineering glycosylation‐directed folding offers a promising route to enhance the production of complex viral glycoproteins in plants.

Hepatitis B virus Vertical Transmission in Booked Pregnant Women in Abuja, Nigeria

Background: Perinatal (vertical) transmission has remained the most important route of spread of Hepatitis B Virus in many endemic areas worldwide. Determining magnitude of vertical transmission to the new born fetuses may allow for planning and modification of strategies to curtail the menace.Objectives: To determine the prevalence of vertical transmission and Sero-prevalence of Hepatitis B virus infection rate in pregnant women in Abuja, Nigeria. Materials and Methods: This was a longitudinal, cohort study involving one hundred and five (105) pregnantwomen that were serially recruited between January 2nd and March 31st, 2013 and tested for serum Hepatitis B surface antigen (HBsAg) using commercial rapid diagnostic Elisa kits. Those women that were positive for HBsAg were tested for envelope antigen(HBeAg) variant. Recruited patients were followed up till delivery. The data was analyzed using statistical package for social sciences (SPSS) version 17. P-value of < 0.05 was considered as statistically significant. The results were presented as Simple per cents and chisquare was employed to test for the significance.Results: There were 8 pregnant women that were positive for HBsAg among 105 consecutive women, giving a prevalence rate of 7.6%. There was no in-utero (vertical) transmission recorded in the study population.Conclusion: The prevalence of HBsAg is relatively high but with zero pre-natal vertical transmission. Proper precautionary measures at delivery are however advocated to keep the vertical transmission at its lowest bearable status.

Evaluation of Hepatitis B viral Serological Patterns and HBV DNA levels in Hepatitis B subjects at Nauth Nnewi, Southeastern Nigeria

Nigeria is one of the countries with the highest incidence of Hepatitis B Virus (HBV) infection worldwide. The inaccessibility and unaffordability of HBV DNA quantification (viral load) assay which is the key laboratory test for therapy initiation, and monitoring is a challenge to HBV management. This study aimed at evaluating the HBV DNA viral load differences across the serological markers of HBV in order to develop a more cost-effective diagnostic algorithm for Hepatitis B management. Cross sectional study design was used with a total of 264 subjects comprising of 88 HBsAg seropositive treatment naïve subjects, 88 HBsAg seropositive subjects on antiviral therapy as case subjects and 88 age-matched apparently healthy HBsAg seronegative individuals were recruited as control subjects. Hepatitis B Virus DNA assay was performed using real time PCR technique, Hepatitis B core Antibody Immunoglobulin M and Hepatitis D Virus Immunoglobulin G assay. Immunochromatography was used for HBV Panel, Hepatitis C Virus assay and Human Immunodeficiency Virus testing. The non-treatment group has higher viral load (M=805.50 IU/ml) compared with treatment group (M = 65.50 IU/ml) (p<0.001). There was a significant difference in the HBV DNA levels of the four serological patterns observed in the study (P< 0.001). Among the four serological patterns observed, the second pattern with positive surface antibody, positive envelope antigen and negative envelope antibody showed highest viral load (M= 46850189.50 IU/ml) followed by the third pattern with negative surface antibody, negative envelope antigen, and negative envelope antibody (M=46555 IU/ml). The first pattern which has negative surface antibody, negative envelope antigen and positive envelope antibody has the lowest viral load (M=21.00 IU/ml) followed by the fourth pattern with positive surface antibody, negative envelope antigen and positive envelope antibody (M=493.00 IU/ml). This study showed that HBV serological markers can predict viral load and should be used as its alternative in resource poor settings.

The impact of hepatotoxic drugs on the outcome of patients with acute deterioration of hepatitis B virus-related chronic disease.

Background and aimsHepatotoxic drugs can worsen outcomes in patients with chronic liver disease (CLD), whereas this negative effect in acute deterioration of hepatitis B virus (HBV)-related CLD (HBV-CLD) is rarely reported. We aimed to assess the impact of hepatotoxic drugs on the outcome of patients with acute deterioration of HBV-CLD.MethodsThis retrospective study included consecutive patients admitted to three medical centers in eastern China from 2015 to 2020 for HBV-related severe liver injury (HBV-SLI) or acute decompensation of cirrhosis (HBV-AD). The prevalence of hepatotoxic drugs and their impact on organ failure, the development of acute-on-chronic liver failure (ACLF), and 90-day survival were evaluated.Results:A total of 335 patients with HBV flare (median age, 44 years; 85.7% male; 38.2% HBV-SLI and 61.8% HBV-AD) were included. Of them, 72 (21.5%) received hepatotoxic drugs, with herbs (44.4%) being the most common form. Patients in the drugs group had a significantly higher prevalence of all types of organ failure except respiratory failure. The multivariate logistic model showed that hepatotoxic drugs raised the risk of developing ACLF by 7.66-fold. ACLF occurrence was the strongest risk factor for 90-day mortality with a hazard ratio of 5.54 in the Cox regression analysis. In contrast, the hepatitis B envelope antigen status and HBV DNA levels had weak associations with the development of organ failure and ACLF.Conclusions:Hepatotoxic drugs are closely associated with the development of organ failure and ACLF, and contribute to reduced 90-day survival rates among patients with acute deterioration of HBV-CLD.

Carriage of Hepatitis B Virus and Risk Factors among Health Care Workers in Ogun State

Background: Health-care workers (HCWs) are often exposed to potentially infectious body fluids-carrying Hepatitis B virus (HBV) from their workplaces. Typically, most asymptomatic HBV carriers-status may remain unnoticed for decades, despite a few percentages of them with vaccination history. In this study, we aimed at investigating asymptomatic carriage of HBV and its associated risk factors among co-health workers ultimately impacting on patients. Methods: Venous blood samples and demographic data were obtained from a cross sectional survey of HCWs categories working in OOUTH, a referral teaching hospital and other selected health facilities in Ogun state. Immuno-chromatographic discs and Enzyme Linked Immuno-Sorbent assay (ELISA) techniques were adopted for the determination and confirmation of the presence of HBsAg, anti-HBs and total anti-HBc in sera. A structured questionnaire was used for obtaining demographic data which were analyzed by regression analytical technique. Results: About 11.44% (43) of the 376 healthcare workers (HCWs), were infected with HBV. The serological marker of viral particles identified in this positive study population included Hepatitis B envelope antigen (53.49%), Hepatitis Core antigen (13.15%), Hepatitis B surface antibodies (3.99%); and Hepatitis B core antibodies (0.80%). A significant association existed between risk factors such as recapping of used needles and carriage of HBV among the HCWs (p-value =0.017). Conclusion: The carriage rate (11.44%) of HBV among HCWs in Ogun state referral health facilities as against the 8% set standard by W.H.O. in 2009, depict the associated risk factors of asymptomatic carriage, pathogenesis and dissemination in and outside of the health facilities.

Luciferase Immunosorbent Assay Based on Multiple E Antigens for the Detection of Chikungunya Virus-Specific IgG Antibodies.

ABSTRACTIn recent years, the chikungunya virus (CHIKV) has continued to spread from local epidemics to nonnative habitats until eventually reaching pandemic status. Nonendemic areas such as China have also emerged as potential epidemic areas of CHIKV. Serological detection of CHIKV is the key to diagnosing and controlling the prevalence of this virus. In this study, we review the progress of the serological detection of the envelope (E) protein in CHIKV, and we provide a novel research assay and ideas for the serological detection of CHIKV. The luciferase immunosorbent assay (LISA) does not require species-specific labeled secondary antibodies for detection, making it universally suitable for tracking samples from various animals or carriers. At present, most research on CHIKV antigen detection technology tends to combine two or more proteins to avoid the decrease in detection ability caused by antigen mutation. Our results indicate that two or more kinds of CHIKV E antigens combined with LISA detection can improve the detection rate of anti-CHIKV immunoglobulin G (IgG) antibodies in CHIKV-infected patient sera and detect antibodies in the early stage of infection accurately and sensitively. After 235 days of infection, the anti-CHIKV IgG antibodies could still be detected in CHIKV-infected patients. All serum samples were tested with a detection rate of 100% after combining various recombinant CHIKV E antigens. Our proposed CHIKV-specific LISA could be a useful tool for serum diagnosis of CHIKV infection and serum epidemic research in areas where CHIKV is endemic, which would help to manage potential epidemics in the future.IMPORTANCE At present, chikungunya virus (CHIKV) is still circulating in some parts of the world, and mutated strains have emerged, making it easier for the virus to spread among humans. With the continuous variation of CHIKV, its antigen variation leads to the decline of detection ability. In addition, the risk of transmission of CHIKV in areas where CHIKV is not endemic, such as China, has increased dramatically, which compels us to enhance the detection capacity of CHIKV and continuously monitor CHIKV antibody levels in the population. Real-time quantitative PCR (RT-PCR) detection technology will not be reliable when the infection time is chronic or in subclinical infection due to decreases in virus concentration, and an antibody detection technology must be adopted. In this study, multiple CHIKV envelope (E) antigens were used to detect anti-CHIKV IgG antibodies in serum for the first time. The new assay is characterized by convenient operation, high detection rate, and high sensitivity and has significance for early warning and monitoring. Moreover, it contributes to the prevention and control of CHIKV.

Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients.

Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3–6 months. Sustained functional cure was analysed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12–24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P ​= ​0.068), and the former groups had significantly higher anti-HBs levels than the later (P ​< ​0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks [odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077–10.224, P ​= ​0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076–139.919, P ​= ​0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.

Antibody levels and protection after Hepatitis B vaccine in adult vaccinated healthcare workers in northern Uganda.

Hepatitis B vaccine has contributed to the reduction in hepatitis B virus infections and chronic disease globally. Screening to establish extent of vaccine induced immune response and provision of booster dose are limited in most low-and-middle income countries (LMICs). Our study investigated the extent of protective immune response and breakthrough hepatitis B virus infections among adult vaccinated healthcare workers in selected health facilities in northern Uganda. A cross-sectional study was conducted among 300 randomly selected adult hepatitis B vaccinated healthcare workers in Lira and Gulu regional referral hospitals in northern Uganda. Blood samples were collected and qualitative analysis of Hepatitis B surface antigen (HBsAg), Hepatitis B surface antigen antibody (HBsAb), Hepatitis B envelop antigen (HBeAg), Hepatitis B envelop antibody (HBeAb) and Hepatitis B core antibody (HBcAb) conducted using ELISA method. Quantitative assessment of anti-hepatitis B antibody (anti-HBs) levels was done using COBAS immunoassay analyzer. Multiple logistic regression was done to establish factors associated with protective anti-HBs levels (≥ 10mIU/mL) among adult vaccinate healthcare workers at 95% level of significance. A high proportion, 81.3% (244/300) of the study participants completed all three hepatitis B vaccine dose schedules. Two (0.7%, 2/300) of the study participants had active hepatitis B virus infection. Of the 300 study participants, 2.3% (7/300) had positive HBsAg; 88.7% (266/300) had detectable HBsAb; 2.3% (7/300) had positive HBeAg; 4% (12/300) had positive HBeAb and 17.7% (53/300) had positive HBcAb. Majority, 83% (249/300) had a protective hepatitis B antibody levels (≥10mIU/mL). Hepatitis B vaccine provides protective immunity against hepatitis B virus infection regardless of whether one gets a booster dose or not. Protective immune response persisted for over ten years following hepatitis B vaccination among the healthcare workers.

Anti-inflammatory, viral replication suppression and hepatoprotective activities of bitter kola - Lime juice, - Honey mixture in HBeAg seropositive patients

Study Background: Bitter kola (Garcinia kola), lime juice, and honey mixture have some traditional but nonscientific applications in the treatment of some infectious diseases due to the phytochemical and phytonutrient components that may have antidiabetic, anti-inflammatory, antipyretic, immunomodulatory, antiatherogenic, antimicrobial, purgative and antiparasitic activities while expression of hepatitis B envelope antigen (HBeAg) is an indication of active hepatitis B virus replication and a high degree of infectiousness. Aim and Objective: This work was therefore designed to determine anti-inflammatory response, possible suppression of active viral replication and liver damage in HBeAg seropositive patients who used bitter kola, lime juice and honey mixture. Materials and Methods: Out of 39 hepatitis B surface antigen and HBeAg seropositive patients who volunteered themselves for the study only 23 volunteers (23; Male: 13; Female: 10; age 34–56 years) were successfully monitored. The mixture is prepared by mixing grounded bitter kola (30 seeds) with 500 ml of Lime Juice and 500 ml of honey. The mixture was kept for 5 days before administration. The mixture was taken by subjects at 4 divided dose for 2 months using 4 teaspoonfuls per dose. Plasma alanine transaminase (ALT) was measured using COBAS C111 autoanalyzer, plasma interleukin-10 (IL-10), Antibodies against hepatitis C virus (anti-HCV), HBeAg, anti-HBeAg, p24 ag-ab by enzyme-linked immunosorbent assay while acid-fast bacilli and Plasmodium were determined in the subjects by microscopic examination of stained smears. Results: The frequency of HBeAg (26.1% [6]) in the patients after the use of bitter kola, lime juice, and honey mixture was lower than the frequency of the viral protein (HBeAg 100% [23]) before the use of the mixture. None of the HBeAg seropositive patients studied expressed anti-HBeAg before the use of bitter kola, lime juice, and honey mixture but 56.5% (13) of the patients expressed anti-HBeAg while 17.4% (4) co-expressed HBeAg + anti-HBeAg after the use of the mixture. There was a significant increase in the plasma value of IL-10 and a significant decrease in the plasma value of ALT in the HBeAg seropositive patients after the use of bitter kola, lime juice, and honey mixture (P < 0.05). Conclusion: Bitter kola, lime juice, and honey mixture could have anti-inflammatory, active viral replication, and liver damage suppression bioactivities in HBeAg seropositive patients as indicated by decrease in HBeAg, expression of anti-HBeAg, decrease in plasma ALT and increase in IL-10 after the use of the mixture.

Effectiveness of hepatitis B hyperimmunglobulin and vaccine in preventing perinatal transmission in children born from a mother with chronic B hepatitis

Background. Viral hepatitis is still one of the important health problems all over the world today. Hepatitis B is a life-threatening liver infection that can cause chronic infections. It increases the risk of death from cirrhosis and hepatocellular carcinoma. One of the most important factors in chronic or acute hepatitis B infection is the age of infection. The earlier the virus is encountered, the greater the risk of chronicity of the disease. Prevention of perinatal transmission of the disease is of great importance. The most effective way to control hepatitis B infection is to prevent contamination and ensure immunity. There is a safe and effective vaccine available that provides 98–100% protection against hepatitis B. Prevention of hepatitis B infection control the development of complications, including chronic disease and liver cancer. The purpose of this study is to evaluate the efficacy of the vaccine and hepatitis immunoglobulin administered to prevent perinatal hepatitis B infection transmission in babies born to mothers with chronic hepatitis B infection. Materials and methods. Fifty-five children born to mothers with chronic hepatitis B infection in our hospital between January 1, 2013 and January 1, 2019 and accepted to participate in the study were included in our study. In retrospective file examination, maternal gestational age, maternal hepatitis B test, delivery method, baby birth weight, baby birth week, whether immunoglobulin and hepatitis B vaccine were administered to these babies in the first 24 hours after birth, hepatitis B vaccine and immunoglobulin administration time, bathroom status, infant hepatitis B tests, additional studies on the child’s viral diseases (hepatitis C, human immunodeficiency virus) and the baby’s liver transaminase tests (aspartate aminotransferase, alanine aminotransferase) were evaluated. The vaccination program of the baby, the control of the mother’s hepatitis B status, the time of the breast milk intake, the height and weight of the baby, the follow-up of the mother during pregnancy and the drug use status were collected. Children previously diagnosed with chronic B hepatitis were excluded from the study. Results. Hepatitis B surface antigen tests were positive in two infants who received three doses of hepatitis B vaccine. The mothers of both of these babies were positive for hepatitis B surface antigen and hepatitis B envelope antigen. Forty-three (78.2 %) patients had a protective antibodies to hepatitis B surface antigen, while 12 (21.8 %) didn’t have it. Conclusions. Hepatitis B serology should be checked in women who live in countries with high risk of chronic hepatitis B infection and who are pregnant, and babies born to these mothers should have hepatitis B vaccine and immunoglobulin.

Blocking T-cell egress with FTY720 extends DNA vaccine expression but reduces immunogenicity.

Optimal immunogenicity from nucleic acid vaccines requires a balance of antigen expression that effectively engages the host immune system without generating a cellular response that rapidly destroys cells producing the antigen and thereby limiting vaccine antigen expression. We investigated the role of the cellular response on the expression and antigenicity of DNA vaccines using a plasmid DNA construct expressing luciferase. Repeated intramuscular administration led to diminished luciferase expression, suggesting a role for immune‐mediated clearance of expression. To investigate the role of cell trafficking, we used the sphingosine 1‐phosphate receptor (S1PR) modulator, FTY720 (Fingolimod), which traps lymphocytes within the lymphoid tissues. When lymphocyte trafficking was blocked with FTY720, DNA transgene expression was maintained at a constant level for a significantly extended time period. Both continuous and staggered administration of FTY720 prolonged transgene expression. However, blocking lymphocyte egress during primary transgene administration did not result in an increase of transgene expression during secondary administration. Interestingly, there was a disconnect between transgene expression and immunogenicity, as increasing expression by this approach did not enhance the overall immune response. Furthermore, when FTY720 was administered alongside a DNA vaccine expressing the HIV gp140 envelope antigen, there was a significant reduction in both antigen‐specific antibody and T‐cell responses. This indicates that the developing antigen‐specific cellular response clears DNA vaccine expression but requires access to the site of expression in order to develop an effective immune response.

Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population.

Data on the long-term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)-negative inactive carriers (ICs) are limited due to small numbers. We compared the long-term prognosis of well-defined ICs with that of age- and gender-matched general population controls. A total of 526 HBeAg-negative patients who demonstrated alanine aminotransferase (ALT) level ≤40U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1year after the start of follow-up were enrolled as ICs. Inactive carriers were divided into two groups: Group A (n=332), whose ALT level was ≤30U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n=194). We determined the long-term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs. There were no significant differences in hepatocellular carcinoma development or all-cause, liver-related, or non-liver-related mortality between Groups A and B. There was no significant difference in all-cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha-fetoprotein level was associated with phase transition. The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.

Vertical transmission of hepatitis B virus: propositions and future directions.

Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides “perfect strategies” to eliminate vertical transmission. However, there is still a notable gap between “perfect strategies” and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B

Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC. The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n= 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67). This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.

Significantly Decreased Islet β Cell Function is Closely Associated with Hyperglycemia in Chronic Hepatitis B Patients.

Aim This study is aimed at the characteristics of glucose metabolism and islet β cell function evaluated by the homeostasis model assessment of β cell function (HOMA-β) value and its risk factors in chronic hepatitis B (CHB) patients. Method This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index under the same glucose metabolism status. The risk factors, characteristics, and differences in glucose metabolism and HOMA-β values between the two groups were analyzed. Results The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) or hepatitis B envelope antigen (HBeAg) (−) status. In addition, under the same glucose metabolism status, the fasting plasma glucose (FPG) levels and 2-hour postprandial plasma glucose (2h-PG) levels in the CHB group were higher, while the HOMA-β values were significantly lower and the homeostasis model assessment of insulin resistance (HOMA-IR) value was not higher than that in the non-HBV group (all P < 0.0001). Further analyses revealed that the main risk factors for abnormal glucose metabolism were HBeAg (−) status and hepatitis B envelope antibody levels. But HBV serological and virological indicators had no effects on the HOMA-β values. Conclusion Islet β cell function in patients with CHB was compromised, which is closely associated with fasting and postprandial hyperglycemia in chronic hepatitis B patients. Further research should be done to verify the compromised islet β cell function and then to investigate the mechanisms behind the effect of hepatitis B virus infection on islet β cell function in CHB patients.

The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis.

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs to prevent infection and suppress viral replication respectively, chronic hepatitis B (CHB) cure remains a remote treatment goal. The viral persistence caused by HBV is account for the chronic infection which increases the risk for developing liver cirrhosis and hepatocellular carcinoma (HCC). HBV virion utilizes various strategies to escape surveillance of host immune system therefore enhancing its replication, while the precise mechanisms involved remain elusive. Accumulating evidence suggests that the proteins encoded by HBV (hepatitis B surface antigen, hepatitis B core antigen, hepatitis B envelope antigen, HBx and polymerase) play an important role in viral persistence and liver pathogenesis. This review summarizes the major findings in functions of HBV encoding proteins, illustrating how these proteins affect hepatocytes and the immune system, which may open new venues for CHB therapies.