Hepatitis-B-Virus-Infektionen und impfinduzierte Immunität: die Rolle von soziodemografischen Determinanten

Zusammenfassung Hintergrund und Ziel Trotz niedriger Prävalenz der Hepatitis-B-Virus-(HBV-)Infektion in Deutschland ist es wichtig, vulnerable Gruppen und Ansatzpunkte für die Prävention zu identifizieren. In ersten Analysen der „Studie zur Gesundheit Erwachsener in Deutschland“ (DEGS1, 2008–2011) waren HBV-Infektion und -Impfung mit sozidemografischen Determinanten assoziiert. In dieser Arbeit werden die Ergebnisse im Detail untersucht. Material und Methoden In DEGS1 lag für 7046 Teilnehmende (Alter: 18–79 Jahre) eine HBV-Serologie vor. Die stattgehabte HBV-Infektion war durch Antikörper gegen das Hepatitis-B-Core-Antigen (Anti-HBc) definiert, die impfinduzierte Immunität durch alleinigen Nachweis von Antikörpern gegen das Hepatitis-B-Surface-Antigen (Anti-HBs). Seroprävalenzen von HBV-Infektions- und -Impfstatus wurden geschlechtsstratifiziert geschätzt und Assoziationen mit Alter, Gemeindegröße, Einkommen, formaler Bildung, Krankenversicherung und Migrationsgeneration in logistischen Regressionen analysiert. Ergebnisse Die HBV-Infektion war bei Männern und Frauen unabhängig mit den Altersgruppen 34–64 und ≥ 65 Jahre, erster Migrationsgeneration und Leben in größeren Gemeinden assoziiert, zudem bei Männern mit niedrigem Einkommen und bei Frauen mit niedriger Bildung. Die impfinduzierte Immunität war bei Männern und Frauen unabhängig mit den Altersgruppen 18–33 und 34–64 Jahre, mittlerer und hoher Bildung und hohem Einkommen assoziiert, darüber hinaus bei Männern mit mittlerem Einkommen und privater Krankenversicherung und bei Frauen mit fehlendem Migrationshintergrund. Diskussion Die Berücksichtigung von Migrationsstatus, Einkommen und Bildung könnte zur zielgenauen Ausrichtung der HBV-Prävention beitragen.

Virus-like particles displaying conserved toxin epitopes stimulate broadly reactive, polyspecific, murine antibody responses capable of snake venom recognition

Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like particles can stimulate a robust and focused antibody response capable of recognising venom toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding to predicted conserved regions of group I phospholipase A2 and three finger toxins, were engineered for display on the surface of hepatitis B core antigen virus like particles and used to immunise female CD1 mice over a 14-weeks. Antibody responses to all venom epitope virus like particles were detectable by ELISA by the end of the immunisation period, although total antibody and epitope specific antibody titres were variable against the different epitope immunogens. Immunoblots using pooled sera demonstrated recognition of various venom components in a diverse panel of six elapid venoms, representing three continents and four genera. Finally, pooled terminal sera was compared to conventional antivenom via quantitative immunoblot, and demonstrated superior recognition of lower-molecular weight elapid venom toxins. This study demonstrates proof-of-principle that virus like particles engineered to display conserved toxin linear epitopes can elicit specific antibody responses in mice which are able to recognise a geographically broad range of elapid venoms.

Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.

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.

An Interesting Case of Isolated False-Reactive Hepatitis B Surface Antigen

The standard serologic markers used to diagnose hepatitis B infection include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), total hepatitis B core antibody (anti-HBc), and IgM antibody to hepatitis B core antigen (IgM anti-HBc). Different markers or combinations of markers are used to identify different phases of HBV infection and determine whether a patient has acute or chronic infection or immunity due to prior infection or vaccination or is seronegative and susceptible to future infection. Isolated HBsAg seropositivity is a peculiar serological pattern that requires investigation. Herein, we present a case of an asymptomatic female without a history of liver disease or evident risk factors for hepatitis, who underwent screening for infectious disease prior to resection of basal cell carcinoma involving her eyelid. The patient’s laboratory testing showed positivity for HBsAg and the HIV 1/2 screen. To investigate, we performed serial dilutions, utilized heterophilicantibody blocking tubes, and repeated analysis using a different commercial assay (Abbott Architect i2000), all in support of a false-positive result attributed to a heterophilic antibody. Hence, we demonstrate that heterophilic antibody interference can result in isolated HBsAg positivity and recommend considering this form of interference in the differential where there is low clinical suspicion for viral infection.

Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus 2019 (COVID-19) have led to tens of millions of cases and millions of deaths around the world. Although more than a year has passed since the emergence of COVID-19, more waves of the pandemic, with new variants of the deadly virus, have been reported. It seems that the virus will continue to infect people for years or decades to come and thus lead to more illnesses and deaths. The experiences last year regarding limiting the transmission of the virus indicate that one or more traditional methods of containment may not be effective; further, even vaccination may not give immunity to society. On the other hand, eliminating the virus using drugs capable of eradicating SARS-CoV-2 from the infected host may not be an achievable goal. Based on these realities and after exploring the mechanism underlying the acquisition of the virus and pathogenesis of COVID-19, we assumed that immune therapy may be a practical option for the containment of SARS-CoV-2. In this study, we repurposed an immune modulator containing two antigens of hepatitis B virus, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (termed NASVAC, Center for Genetic Engineering and Biotechnology, CIGB, Havana, Cuba), to gain insight into its role against SARS-CoV-2. NASVAC induced cytokines of innate immunity following nasal administration and prevented all 20 volunteers from being diagnosed with SARS-CoV-2 during the two weeks of usage. Four volunteers were infected with SARS-CoV-2 two weeks after the end of NASVAC administration; three of them showed almost no symptoms and recovered without any intervention, and one with several comorbidities attended a hospital for four days and recovered completely. In conclusion, the administration of NASVAC to subjects at risk of SARS-CoV-2 infection was safe. The pattern of cytokine responses and absence of infection or mild COVID-19 infection of the subjects involved in the study are preliminary evidence indicating that this product may prevent or suppress SARS-CoV-2 infection at the initial stages of SARS-CoV-2 acquisition and/or replication and deserve further exploratory trials to confirm the capacity of NASVAC as pre/postexposure prophylaxis or pre-emptive therapy in the context of SARS-CoV-2 infection.

Evaluation of the Seroprevalence of Infectious Diseases in 2,445 in vitro Fertilization Cycles

Objective To evaluate the seroprevalence of positive markers for syphilis, human immunodeficiency virus (HIV) I and II, human T cell lymphotropic virus (HTLV) I and II, and hepatitis B and C among women undergoing in vitro fertilization (IVF). Methods We conducted a retrospective analysis among patients who underwent IVF, between January 2013 and February 2016, and who had complete screening records. Results We analyzed 1,008 patients who underwent IVF, amounting to 2,445 cycles. Two patients (0.2%) tested positive for HIV I and II and none for HTLV I and II. Three patients (0.3%) had positive screening for syphilis, and two (0.2%) had positive hepatitis C antibody test (anti-HCV). A positive hepatitis B virus surface antigen (HbsAg) test was observed in 4 patients (0.4%), while 47 (4.7%) patients were positive for IgG antibody to hepatitis B core antigen (anti-HbC IgG), and only 1 (0.1%) was positive for IgM antibody to hepatitis B core antigen (anti-HbC IgM). The anti-HbS test was negative in 659 patients (65.3%). Only 34.7% of the patients had immunity against the Hepatitis B virus. Patients with an anti-HbS negative result were older than those with a hepatitis B test (anti-HbS) positive result (36.3 versus 34.9; p < 0.001). Conclusion The present study showed lower infection rates than the Brazilian ones for the diseases studied in patients undergoing IVF. Only a few patients were immunized against hepatitis B.

Potential of Nanoparticles Chitosan for Delivery pcDNA3.1-SB3-HBcAg

Hepatitis B virus (HBV) is a DNA virus that causes hepatitis in humans. This study aims to prepare a Hepatitis DNA vaccine. he optimized base sequence of the SB3-HBcAg gene was derived from the nucleotide base sequence of the Hepatitis B core antigen B3 HBcAg subgenotype, and then Cloning of the pcDNA3.1-SB3-HBcAg has been successfully performed on E. coli DH5α and confirmed by PCR, restriction analysis and sequencing. The propagated plasmids were prepared as DNA-chitosan complex and physiochemical characterized using Particle Size Analyzer. Complex with a 4:1 (wt/wt) ratio of DNA with 0.04% concentration and chitosan have a mean diameter of 231.7 nm and zeta potential +12.3 mV and the value of Cytotoxicity Assay 80-90% as compared to the untreated cells that used as negative control, so it can be concluded that nanoparticles chitosan has good potential as a carrier agent for pcDNA3.1-SB3-HBcAg.