scholarly journals Dynamics of the Immune Response in Acute Hepatitis B Infection

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Femke Stelma ◽  
Sophie B Willemse ◽  
Robin Erken ◽  
Annikki de Niet ◽  
Marjan J Sinnige ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Acute Hepatitis ◽  
Nk Cells ◽  
T Cell Responses ◽  
Hbv Infection ◽  
Cell Responses ◽  
B Virus ◽  
Acute Hepatitis B

Abstract Background Acute hepatitis B virus infection in adults is generally self-limiting but may lead to chronicity in a minority of patients. Methods We included 9 patients with acute hepatitis B virus (HBV) infection and collected longitudinal follow-up samples. Natural killer (NK) cell characteristics were analyzed by flowcytometry. HBV-specific T-cell function was analyzed by in vitro stimulation with HBV peptide pools and intracellular cytokine staining. Results Median baseline HBV DNA load was 5.12 log IU/mL, and median ALT was 2652 U/mL. Of 9 patients, 8 cleared HBsAg within 6 months whereas 1 patient became chronically infected. Early time points after infection showed increased CD56bright NK cells and an increased proportion of cells expressing activation markers. Most of these had normalized at week 24, while the proportion of TRAIL-positive CD56bright NK cells remained high in the chronically infected patient. In patients who cleared HBV, functional HBV-specific CD8+ and CD4+ responses could be observed, whereas in the patient who developed chronic infection, only low HBV-specific T-cell responses were observed. Conclusions NK cells are activated early in the course of acute HBV infection. Broad and multispecific T-cell responses are observed in patients who clear acute HBV infection, but not in a patient who became chronically infected.

scholarly journals Effect of HIV Infection and Antiretroviral Therapy on Hepatitis B Virus (HBV)–Specific T Cell Responses in Patients Who Have Resolved HBV Infection

2005 ◽  
Vol 191 (7) ◽  
pp. 1169-1179 ◽  
Author(s):  
R. Monica Lascar ◽  
A. Ross Lopes ◽  
Richard J. Gilson ◽  
Claire Dunn ◽  
Ruth Johnstone ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hepatitis B ◽  
Hiv Infection ◽  
T Cell Responses ◽  
Hbv Infection ◽  
Cell Responses ◽  
B Virus

scholarly journals A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 969
Author(s):  
Dorien De Pooter ◽  
Ellen Van Gulck ◽  
Antony Chen ◽  
Claire F. Evans ◽  
Jean-Marc Neefs ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Immune Responses ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Hbv Infection ◽  
Cell Responses ◽  
B Virus

Despite the availability of an effective prophylactic vaccine for more than 30 years, nearly 300 million people worldwide are chronically infected with the hepatitis B virus (HBV), leading to 1 death every 30 s mainly from viral hepatitis-related cirrhosis and liver cancer. Chronic HBV patients exhibit weak, transient, or dysfunctional CD8+ T-cell responses to HBV, which contrasts with high CD8+ T-cell responses seen for resolvers of acute HBV infection. Therefore, a therapeutic DNA vaccine was designed, expressing both HBV core and polymerase proteins, and was sequence optimized to ensure high protein expression and secretion. Although the vaccine, administered intramuscularly via electroporation, had no effect on plasma viral parameters in a mouse model of persistent HBV infection, it did induce robust HBV-specific immune responses in healthy and adeno-associated hepatitis B virus (AAV-HBV) infected mice as well as in healthy non-human primates.

scholarly journals Type I Interferon Signaling Prevents Hepatitis B Virus-Specific T Cell Responses by Reducing Antigen Expression

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Keigo Kawashima ◽  
Masanori Isogawa ◽  
Susumu Hamada-Tsutsumi ◽  
Ian Baudi ◽  
Satoru Saito ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Type I Interferon ◽  
T Cell Responses ◽  
Antigen Expression ◽  
Type I ◽  
Interferon Signaling ◽  
Cell Responses ◽  
B Virus

ABSTRACT Robust virus-specific CD8+ T cell responses are required for the clearance of hepatitis B virus (HBV). However, the factors that determine the magnitude of HBV-specific CD8+ T cell responses are poorly understood. To examine the impact of genetic variations of HBV on HBV-specific CD8+ T cell responses, we introduced three HBV clones (Aa_IND [Aa], C_JPN22 [C22], and D_IND60 [D60]) that express various amounts of HBV antigens into the livers of C57BL/6 (B6) (H-2b) mice and B10.D2 (H-2d) mice. In B6 mice, clone C22 barely induced HBV-specific CD8+ T cell responses and persisted the longest, while clone D60 elicited strong HBV-specific CD8+ T cell responses and was rapidly cleared. These differences between HBV clones largely diminished in H-2d mice. Interestingly, the magnitude of HBV-specific CD8+ T cell responses in B6 mice was associated with the HB core antigen expression level during the early phase of HBV transduction. Surprisingly, robust HBV-specific CD8+ T cell responses to clone C22 were induced in interferon-α/β receptor-deficient (IFN-αβR–/–) (H-2b) mice. The induction of HBV-specific CD8+ T cell responses to C22 in IFN-αβR–/– mice reflects enhanced HBV antigen expression because the suppression of antigen expression by HBV-specific small interfering RNA (siRNA) attenuated HBV-specific T cell responses in IFN-αβR–/– mice and prolonged HBV expression. Collectively, these results suggest that HBV genetic variation and type I interferon signaling determine the magnitude of HBV-specific CD8+ T cell responses by regulating the initial antigen expression levels. IMPORTANCE Hepatitis B virus (HBV) causes acute and chronic infection, and approximately 240 million people are chronically infected with HBV worldwide. It is generally believed that virus-specific CD8+ T cell responses are required for the clearance of HBV. However, the relative contributions of genetic variation and innate immune responses to the induction of HBV-specific CD8+ T cell responses are not fully understood. In this study, we discovered that different clearance rates between HBV clones after hydrodynamic transduction were associated with the magnitude of HBV-specific CD8+ T cell responses and initial HB core antigen expression. Surprisingly, type I interferon signaling negatively regulated HBV-specific CD8+ T cell responses by reducing early HBV antigen expression. These results show that the magnitude of the HBV-specific CD8+ T cell response is regulated primarily by the initial antigen expression level.

scholarly journals Acute Hepatitis B Co-infection in HIV-Infected Patients Despite Prior Hepatitis B Vaccination

2017 ◽  
Vol 11 (4) ◽  
Author(s):  
S. Rolland ◽  
L. Antonova ◽  
J. Powis ◽  
T. Murdoch ◽  
D. Wong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Acute Hepatitis ◽  
Elevated Risk ◽  
Vaccination Status ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Hiv Patients ◽  
B Virus ◽  
Acute Hepatitis B

Clinicians often assume that patients vaccinated for hepatitis B virus (HBV) have immunity. We report three cases of acute HBV infection in HBV-vaccinated HIV patients. These cases illustrate that patients at an elevated risk of HBV exposure presenting with acute hepatitis should be tested for HBV infection regardless of previous vaccination status.

Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B

2018 ◽  
Vol 69 (3) ◽  
pp. 584-593 ◽  
Author(s):  
Franziska Rinker ◽  
Christine L. Zimmer ◽  
Christoph Höner zu Siederdissen ◽  
Michael P. Manns ◽  
Anke R.M. Kraft ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
T Cell Responses ◽  
Cell Responses ◽  
B Virus ◽  
Negative Chronic Hepatitis

scholarly journals Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen.

1991 ◽  
Vol 174 (6) ◽  
pp. 1565-1570 ◽  
Author(s):  
A Penna ◽  
F V Chisari ◽  
A Bertoletti ◽  
G Missale ◽  
P Fowler ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Acute Hepatitis ◽  
Mononuclear Cells ◽  
Cell Injury ◽  
Hbv Infection ◽  
Chronic Patients ◽  
Ctl Response ◽  
B Virus ◽  
Acute Hepatitis B

The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.

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