Hepatitis B virus(HBV)infection is a serious global public health problem.The infection may be transmitted through sexual intercourse,parenteral contact or from an infected mother to the baby at birth and,if contracte...Hepatitis B virus(HBV)infection is a serious global public health problem.The infection may be transmitted through sexual intercourse,parenteral contact or from an infected mother to the baby at birth and,if contracted early in life,may lead to chronic liver disease,including cirrhosis and hepatocellular carcinoma.On the basis of the HBV carrier rate,the world can be divided in 3 regions of high,medium and low endemicity.The major concern is about high endemicity countries,where the most common route of infection remains vertical transmission from mother to child.Screening of all pregnant women and passive immunization with human hepatitis B immunoglobulin are not affordable for many developing countries.The infection rate can be reduced by modifying behavior,improving individual education,testing all blood donations,assuring asepsis in clinical practice and screening all pregnant women.However,availability of a safe and efficacious vaccine and adoption of appropriate immunization strategies are the most effective means to prevent HBV infection and its consequences.The unsolved problem for poorest countries,where the number of people currently infected is high,is the cost of the vaccine.A future challenge is to overcome the social and economic hurdles of maintaining and improving a prevention policy worldwide to reduce the global burden of the disease.展开更多
Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of...Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection： （1） These influence acquisition of chronic HBV carrier state, （2） They are important in the context of liver damages, （3） Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach （vaccine therapy）. The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV- specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.展开更多
AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral ...AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunot展开更多
INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant ...INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant association among persistentinfection, liver cirrhosis and hepatocellularcarcinoma[1-3].展开更多
Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections stil...Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.展开更多
AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were s...AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.展开更多
Hepatitis A is the most common form of acute viral hepatitis in the world.Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the...Hepatitis A is the most common form of acute viral hepatitis in the world.Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the level of socioeconomic development.The anti-hepatitis A virus(HAV)seroprevalence rate is presently decreasing in many parts of the world,but in less developed regions and in several developing countries,HAV infection is still very common in the first years of life and seroprev-alence rates approach 100%.In areas of intermediate endemicity,the delay in the exposure to the virus has generated a huge number of susceptible adolescents and adults and significantly increased the average age at infection.As the severity of disease increases with age,this has led to outbreaks of hepatitis A.Several factors contribute to the decline of the infection rate,including rising socioeconomic levels,increased access to clean water and the availability of a hepatitis A vaccine that was developed in the 1990s.For populations with a high proportion of susceptible adults,implementing vaccination programs may be considered.In this report,we review available epidemiological data and implementation of vaccination strategies,particularly focusing on developing countries.展开更多
Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Ve...Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.展开更多
甲型病毒性肝炎(hepatitis A,简称甲肝)是由甲型肝炎病毒(hepatitis A virus,HAV)引起的以肝脏损伤为主的急性肠道传染性疾病。对于HAV的研究很早就已展开,但其大部分致病机理并未确认。本文阐述了近期研究发现的有关HAV的结构、病毒感...甲型病毒性肝炎(hepatitis A,简称甲肝)是由甲型肝炎病毒(hepatitis A virus,HAV)引起的以肝脏损伤为主的急性肠道传染性疾病。对于HAV的研究很早就已展开,但其大部分致病机理并未确认。本文阐述了近期研究发现的有关HAV的结构、病毒感染与免疫及其逃逸机制,并对甲肝疫苗及治疗药物的发展现状进行概述。展开更多
文摘Hepatitis B virus(HBV)infection is a serious global public health problem.The infection may be transmitted through sexual intercourse,parenteral contact or from an infected mother to the baby at birth and,if contracted early in life,may lead to chronic liver disease,including cirrhosis and hepatocellular carcinoma.On the basis of the HBV carrier rate,the world can be divided in 3 regions of high,medium and low endemicity.The major concern is about high endemicity countries,where the most common route of infection remains vertical transmission from mother to child.Screening of all pregnant women and passive immunization with human hepatitis B immunoglobulin are not affordable for many developing countries.The infection rate can be reduced by modifying behavior,improving individual education,testing all blood donations,assuring asepsis in clinical practice and screening all pregnant women.However,availability of a safe and efficacious vaccine and adoption of appropriate immunization strategies are the most effective means to prevent HBV infection and its consequences.The unsolved problem for poorest countries,where the number of people currently infected is high,is the cost of the vaccine.A future challenge is to overcome the social and economic hurdles of maintaining and improving a prevention policy worldwide to reduce the global burden of the disease.
基金Supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan to Sk. Md. Fazle Akbar, No. C17590651 and Morikazu Onji, No. C17590652
文摘Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection： （1） These influence acquisition of chronic HBV carrier state, （2） They are important in the context of liver damages, （3） Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach （vaccine therapy）. The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV- specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.
基金Supported by in part Grant-in-Aid for Scientific Research (C) (toK.K)
文摘AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ staining. RESULTS: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P<0.05). Similarly, fewer HBV specific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n - 6, P<0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg cells. CONCLUSION: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunot
基金Project supported by the grant from Science Foundation of Ministry of Health of China, No. 96-1-347.
文摘INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant association among persistentinfection, liver cirrhosis and hepatocellularcarcinoma[1-3].
文摘Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.
基金Serum Institute of India, Pune, India and Indian Council for Medical Research (ICMR) New Delhi, India
文摘AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.
文摘Hepatitis A is the most common form of acute viral hepatitis in the world.Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the level of socioeconomic development.The anti-hepatitis A virus(HAV)seroprevalence rate is presently decreasing in many parts of the world,but in less developed regions and in several developing countries,HAV infection is still very common in the first years of life and seroprev-alence rates approach 100%.In areas of intermediate endemicity,the delay in the exposure to the virus has generated a huge number of susceptible adolescents and adults and significantly increased the average age at infection.As the severity of disease increases with age,this has led to outbreaks of hepatitis A.Several factors contribute to the decline of the infection rate,including rising socioeconomic levels,increased access to clean water and the availability of a hepatitis A vaccine that was developed in the 1990s.For populations with a high proportion of susceptible adults,implementing vaccination programs may be considered.In this report,we review available epidemiological data and implementation of vaccination strategies,particularly focusing on developing countries.
文摘Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.
文摘甲型病毒性肝炎(hepatitis A,简称甲肝)是由甲型肝炎病毒(hepatitis A virus,HAV)引起的以肝脏损伤为主的急性肠道传染性疾病。对于HAV的研究很早就已展开,但其大部分致病机理并未确认。本文阐述了近期研究发现的有关HAV的结构、病毒感染与免疫及其逃逸机制,并对甲肝疫苗及治疗药物的发展现状进行概述。
