Recombinant hepatitis B core antigen carrying preS1 epitopes induce immune response against chronic HBV infection

Abstract Background Hepatitis B vaccination during childhood is key to reduce the prevalence of Hepatitis B virus (HBV) infection. In Senegal, a highly endemic country, the three-dose hepatitis B vaccine and the birth dose vaccine were introduced in the Expanded Programme on Immunization (EPI) in 2004 and 2016 respectively. This study aimed to determine chronic HBV infection prevalence, hepatitis B vaccination status and vaccine immunity among children in Senegal. Methods A cross-sectional study including HBV screening was conducted at home among children aged 6 months to 15 years (i.e. born after the introduction of the HBV vaccine in the EPI) in the rural zone of Niakhar. Dried Blood Spot (DBS) samples were collected for the detection of HBsAg, anti-HBc Ab and anti-HBs Ab using chemoluminescence. Vaccination status was assessed using information on vaccination cards. Detectable vaccine immunity was defined with an adjusted DBS threshold of DOI≥0.36 IU/mL (corresponding to 10 IU/mL in venous blood sampling). Results Between October and December 2018, 455 children were enrolled. Preliminary results show that 7/455 (1.5%) had been in contact with HBV (positive anti-HBc Ab) and 5/455 (1.1%) had chronic HBV infection (positive HBsAg). Only 161/455 (35.4%) children had a vaccination card available. Among those, 150/161 (93.2%) received at least 3 doses of hepatitis B vaccine, of which 83/150 (55.3%) had detectable vaccine immunity. The proportion of children with detectable vaccine immunity was significantly higher in children <5 years than in children aged 5-9 and 10-15 (72.3% versus 47.3%, p = 0.006 and 72.3% versus 14.3%, p < 0.001). Conclusions Preliminary results suggest a low prevalence of HBV chronic infection among children born after the introduction of HBV vaccination in Senegal. However, detectable vaccine immunity rapidly decreases with age among vaccinated children, signalling a need for further studies on the immune response to HBV vaccination in this context. Key messages HBV chronic infection is low among children born after the introduction of HBV vaccination in Senegal. Further studies on the immune response to HBV vaccination in this context are needed.

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Antiviral Activity and Pharmacokinetics of the HBV Capsid Assembly Modulator GLS4 in Patients with Chronic HBV Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciaa961 ◽

2020 ◽

Author(s):

Hong Zhang ◽

Fengjiao Wang ◽

Xiaoxue Zhu ◽

Yunfu Chen ◽

Hong Chen ◽

...

Keyword(s):

Hepatitis B ◽

Antiviral Activity ◽

Accumulation Rate ◽

Hbv Infection ◽

Controlled Study ◽

Core Antigen ◽

Capsid Assembly ◽

Chronic Hbv Infection ◽

Chronic Hbv ◽

The Mean

Abstract Background GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that can inhibit HBV replication by interfering with the assembly and disassembly of HBV nucleocapsid. Here, we evaluated its antiviral activity, pharmacokinetics (PK), and tolerability in a double-blind, randomized, parallel, entecavir-controlled study. Methods Twenty four chronic HBV patients were randomized to receive a 28-day course of GLS4 (120 or 240 mg) and ritonavir (100 mg) combination (cohorts A and B, respectively) or entecavir treatment (cohort C) at a 1:1:1 ratio. Patients were followed-up for 40 days in a phase 1b study. Results The GLS4/ritonavir combination was a tolerated combination for the treatment of chronic HBV infection. A total of two, three, and three subjects presented with alanine aminotransferase flare in cohorts A, B and C, respectively. This contributed to the withdrawal of one, two, and one patient from cohorts A, B and C, respectively. The mean Ctrough of GLS4 was 205–218 ng/mL, which was approximately 3.7–3.9 times the EC90 (55.8 ng/mL), with a lower accumulation (accumulation rate: 1.1–2.0). In cohorts A, B and C, the mean declines in HBV DNA after 28 days of treatment were -1.42, -2.13, and -3.5 log10 IU/mL; in hepatitis B surface antigen were -0.06, -0.14, and -0.33 log10 IU/mL; in pregenomic RNA were -0.75, -1.78, and -0.96 log10 copies/mL; and in hepatitis B core antigen (were -0.23, -0.5, and -0.44 log10 U/mL, respectively. Conclusions Treatment with 120 mg GLS4 was tolerated and had antiviral activity in patients with chronic HBV infection.

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Characterization of the immune response to the hepatitis B virus X protein in acute and chronic HBV infection

Journal of Hepatology ◽

10.1016/0168-8278(89)90540-0 ◽

1989 ◽

Vol 9 ◽

pp. S182

Author(s):

M. Levrero ◽

A. Franco ◽

E. De Marzio ◽

C. Balsano ◽

M.L. Avantaggiati ◽

...

Keyword(s):

Immune Response ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

X Protein ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

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Plasmacytoid dendritic cells and their role in the immunopathogenesis of viral infections for example hepatitis B

Journal Infectology ◽

10.22625/2072-6732-2019-11-2-14-19 ◽

2019 ◽

Vol 11 (2) ◽

pp. 14-19 ◽

Cited By ~ 1

Author(s):

R. R. Khodzhibekov ◽

O. N. Khokhlova ◽

A. R. Reizis ◽

G. M. Kozhevnikova

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Unique Type ◽

Antiviral Immune Response ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

A new approach in understanding the mechanisms of immune response in viral hepatitis is the discovery of a unique type of immune cells – plasmocytoid dendritic cells (pDCs). Plasmocytoid dendritic cells (pDCs) are cells of lymphoid origin and morphologically resemble plasma cells. Functionally, they are professional IFN-a-producing cells that play an important role in antiviral immune response. Data on the mechanisms of PDCs participation in hepatitis B virus infection are few and contradictory. In chronic HBV infection, the role of pDCs remains mysterious and poorly understood with conflicting circulating blood pDCs results that show differently that they are not affected or reduced. However, functional disorders of pDCs were observed in patients with chronic HBV infection. The establishment of these mechanisms, as well as the search for the cause of hepatitis B virus latency and the formation of chronic infection remains one of the important and promising areas of scientific activities today.

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The Multiple Functions of B Cells in Chronic HBV Infection

Frontiers in Immunology ◽

10.3389/fimmu.2020.582292 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ying Cai ◽

Wenwei Yin

Keyword(s):

Immune Response ◽

Chronic Hepatitis ◽

B Cells ◽

Hepatitis B ◽

B Cell ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Multiple Functions ◽

Chronic Hbv ◽

B Cell Subsets

Chronic hepatitis B virus (HBV) infection is one of the main causes of liver diseases, of which the natural history and clinical outcomes are associated with the role of B cells. As humoral immune cells, B cells play a critical role in the process of anti-HBV antibody production. In addition, some studies have also characterized other B cell subsets involved in antigen presentation and regulating the immune response beyond antibody secretion. However, not all B cell subsets play a positive role in the immune response to chronic HBV infection, and various B cell subsets jointly mediate persistent HBV infection, tolerance, and liver damage. Thus, we further sought to elucidate the multiple functions of B cells to gain novel insight into the understanding of chronic hepatitis B (CHB) pathogenesis. We also reviewed the current immunotherapies targeting B cells to explore novel therapeutic interventions for the treatment of chronic HBV infection.

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