scholarly journals Naturally Occurring Hepatitis B Virus B-Cell and T-Cell Epitope Mutants in Hepatitis B Vaccinated Children

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yu-Min Lin ◽  
Guey-Mei Jow ◽  
Shu-Chi Mu ◽  
Bing-Fang Chen

To control hepatitis B virus (HBV) infection, a universal HBV vaccination program for infants was launched in Taiwan in 1984. The aim of this study was to investigate the role of B-cell and T-cell epitope variations of HBsAg and polymerase in HBV infection in vaccinated children. One hundred sixty-three sera from vaccinated children were enrolled randomly. HBV serum markers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were detected by ELISA. Nucleotide sequences encoding the S and the pre-S regions of HBsAg were analyzed in all HBsAg positive sera. Five children were HBsAg positive. Sequence analysis of S, pre-S, and overlapped polymerase (P) genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found in the “a” determinant. Fifteen, six, and eight amino acid substitutions within B-cell and T-cell epitopes of S, pre-S, and P regions were detected, respectively. Several immune-epitope mutants, such as S45T/A, N131T, I194V, and S207N in S, were detected in all isolates. In conclusion, our results suggested that these naturally occurring immunoepitope mutants, which changed their immunogenicity leading to escape from immune response, might cause HBV infection.

Hepatology ◽  
1997 ◽  
Vol 26 (4) ◽  
pp. 1027-1034 ◽  
Author(s):  
A Bertoletti ◽  
S Southwood ◽  
R Chesnut ◽  
A Sette ◽  
M Falco ◽  
...  

1993 ◽  
Vol 67 (4) ◽  
pp. 2376-2380 ◽  
Author(s):  
A Bertoletti ◽  
F V Chisari ◽  
A Penna ◽  
S Guilhot ◽  
L Galati ◽  
...  

2003 ◽  
Vol 84 (1) ◽  
pp. 139-146 ◽  
Author(s):  
Una Lazdina ◽  
Mats Alheim ◽  
Jessica Nyström ◽  
Catharina Hultgren ◽  
Gallina Borisova ◽  
...  

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Shigeru Kusumoto ◽  
Kensei Tobinai

Abstract Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody—rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab + cyclophosphamide + hydroxydaunorubicin + vincristine + prednisone/prednisolone)—is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%–80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%–24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection.


2012 ◽  
Vol 13 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Qiuyan Liu ◽  
Yuanyuan Zheng ◽  
Yizhi Yu ◽  
Qinchun Tan ◽  
Xinping Huang

2015 ◽  
Vol 24 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Mihai Voiculescu

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity.Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation.It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered. Abbreviations: ALT: alanine aminotransferase; APC: antigen presenting cells; cccDNA: covalently closed circular DNA; HBIG: hepatitis B immunoglobulin; HbsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CTL: cytotoxic T lymphocyte; IFN: interferon; NUC: nucleos(t)ide analogues; pg RNA: pre genomic RNA; TLR: toll-like receptors; TOL: T cell receptors.


Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 343-354 ◽  
Author(s):  
Tian-Ying Zhang ◽  
Xue-Ran Guo ◽  
Yang-Tao Wu ◽  
Xiao-Zhen Kang ◽  
Qing-Bing Zheng ◽  
...  

ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.


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