增强乙型肝炎疫苗免疫效果的研究进展

乙肝疫苗对于控制乙型肝炎病毒感染十分重要.近年人们仍在根据免疫学理论和生物工程技术进展不断研发更加科学有效的新型乙肝疫苗.就新型乙肝疫苗设计的免疫机制和提高免疫效果的关键因素作出综述.     

血源乙肝疫苗的安全性

我国是乙肝的高发病区,全国有10％以上的人感染乙肝病毒,占世界总数的一半左右。为了消灭乙型肝炎,卫生部颁发了“全国乙肝疫苗免疫接种实施方案”,并从92年1月1日起在全国各地逐步推行乙肝疫苗免疫接种工作。86年1月我国批准生产血源乙肝疫苗,92 年1月1日起在全国各地逐步推行乙肝疫苗免疫接种工作。     

海口市人群乙型病毒性肝炎血清学调查分析

目的了解海口市人群乙型肝炎表面抗原(HBs Ag)和乙型肝炎表面抗体(抗-HBs)状况,评价乙型肝炎疫苗(乙肝疫苗)纳入儿童计划免疫后的效果。方法采用分层整群抽样方法,按接种率高、中、低分为3层,每层采取完全随机的方式将调查对象分为8个年龄组,并采集静脉血进行HBs Ag和抗-HBs检测分析。结果共筛选调查对象1 162人,乙肝疫苗接种率为74.18%,15岁以下者乙肝疫苗接种率(83.61%)明显高于15岁以上者(58.82%)。HBs Ag阳性率为5.94%,15岁以下者HBs Ag阳性率(4.16%)低于15岁以上者阳性率(8.82%)。抗-HBs阳性率为57.32%,15岁以下者与15岁以上者抗-HBs阳性率分别为60.69%和51.81%。接种率越高地区HBs Ag阳性率越低,抗-HBs阳性率越高。结论海口市乙肝疫苗纳入儿童计划免疫效果显著,明显降低了15岁以下儿童HBs Ag阳性率,抗-HBs阳性率上升幅度明显,乙型肝炎的控制成效显著。     

乙型肝炎疫苗与卡介苗、百白破混合菌苗的联合免疫效果观察

本文报道150名HBsAg阴性产妇所生新生儿在实施计划免疫的同时,1、2组分别接种10μg、20μg乙肝疫苗,3组不接种乙肝疫苗,以了解乙肝疫苗与卡介苗、百白破联合免疫的免疫应答。结果表明:1.2组抗-HBc达到有效保护的(P/N≥5)为93.18％和89.58％,无显著差异;两组均未检出HBV标志物,但是未注射乙肝疫苗组HBV感染达6.67％。乙肝疫苗与卡介苗、百白破联合免疫应答是好的,抗原间无干扰,从而证明乙肝疫苗不但能有效地控制乙型肝炎,并能纳入扩大免疫规划。     

深圳康泰生物制品有限公司的基因工程乙肝疫苗车间落成

深圳康泰生物制品有限公司的基因工程乙肝疫苗车间落成乙型肝炎是一种严重威胁人类的传染病,我国是高发区。国家对乙肝的预防十分重视。在八十年代前人们对该病的防治束手无策。八十年代研制成功的血源乙肝疫苗。对防治乙肝有显著作用。但这种疫苗受血源及安全性的限制。...     

乙肝疫苗免疫保护接种乙肝病毒的黑猩猩获得成功

<正> 在男性同性恋者中,对乙肝疫苗的效力进行了观察。试验发现接种乙肝疫苗的同性恋者患乙型肝炎人数明显比不接种疫苗的同类人少。可以设想疫苗对处于潜伏期的个体有抑制乙肝临床表现的作用。为检验这个假设,先给四只黑猩猩注射一定量确定滴度的乙肝病毒,然后分别在4-72小时后接种第一针乙肝疫苗,第二和第三针备在2和6周后接种。     

简化接种方案同时注射百白破小儿麻痹和乙肝疫苗——对五种抗原的免疫应答

<正>大多数发展中国家中乙型肝炎呈地方性流行,只有在儿童早期完成预防接种,才能控制该病的感染。为了解决乙肝疫苗能否与计划免疫六种制品同时使用,以适应形势需要。作者们在塞内加尔进行了三组现场试验:(1)单独接种乙肝疫苗;(2)一起接种百白破小儿麻痹疫苗;(3)同时接种百白破小儿麻痹疫苗加乙肝疫苗。并研究了儿童对HBsAg,破类、白类和百白咳的血     

冷冻干燥对重组酵母乙型肝炎疫苗效力(抗原性)的影响

重组酵母乙型肝炎疫苗(酵母乙肝疫苗)加入保护剂后冷冻干燥,观察是否影响疫苗抗原性和稳定性。按5％和1％的比例,在酵母乙肝疫苗原液中分别加入蔗糖和明胶,低温冷冻干燥,制备3批冻干疫苗,分别进行体外相对效力和小鼠ED50测定。加保护剂冻干后酵母乙肝疫苗体外相对效力和小鼠ED50值较冻干前改变不大,而4℃放置和热加速后的稳定性均优于液体疫苗。因此现有酵母乙肝疫苗加入保护剂冻干后,显著提高了疫苗的稳定性,为进一步制备稳定的疫苗参考品打下了初步基础。     

乙型肝炎多表位DNA疫苗的发展趋势

乙型肝炎多表位DNA疫苗(epitopeDNAvaccine,minigenes/epigenes)是指多个表位(包括T细胞、B细胞等表位)经过优化组合,以能产生高效的细胞、体液免疫应答进而清除HBV病毒为目的而得到的新型乙肝疫苗。该文介绍近年来国内外在乙型肝炎多表位DNA疫苗方面的发展趋势。     

新生儿国产重组(酵母)乙型肝炎疫苗免疫效果考核

为了考核新生儿接种国产重组(酵母)乙型肝炎(乙肝)疫苗后的免疫效果,并与血源乙肝疫苗效果比较。对1997年出生并接种重组(酵母)乙肝疫苗的新生儿隔年随访一次,采血检测乙肝病毒表面抗原(HBsAg),乙肝病毒表面抗体(抗-HBs)和乙肝病毒核心抗体(抗-HBc),1998年以后对乙肝免疫人群开展急性乙肝发病监测。显示五年期间3次随访检测HBsAg阳性率平均为1.5%,较免前本底的HBsAg阳性率呈较大幅度下降,疫苗保护率为83%(95%可信区间为76.97%~89.02%),无论母亲HBsAg阳性或阴性,使用不同乙肝疫苗的儿童HBsAg阳性率没有统计学差异。接受重组(酵母)乙肝疫苗免疫的对象中,无一例急性乙肝病例报告。重组(酵母)乙肝疫苗有较好的近期保护效果和免疫原性,与以前使用血源乙肝疫苗效果相当。     

Viral interference: A potential therapeutic method for chronic viral hepatitis?

Viral interference exists between different viral hepatitis. Acute Hepatitis C virus (HCV) super-infection on Hepatitis B virus (HBV) chronic carriers showed an inhibition of the HBV genome. And acute HBV super-infection on HCV chronic carriers indicated a similar interaction. In these cases, if the acute liver viral super-infection presents a self-limited course, the patients may be free from both viral infections or at least with undetectable underlying chronic viremia. The mechanism of viral interference is still undefined. Anyway this still leads to the hypothesis of using one hepatitis virus (live attenuated vaccine) to treat another hepatitis virus.     

从动物模型看乙型病毒性肝炎致病机制的研究进展

乙型肝炎病毒(Hepatitis B virus,HBV)是通过血液和体液传播的嗜肝DNA病毒,尽管有有效的预防疫苗,乙型病毒性肝炎仍是我国乃至全球人类健康的重大威胁。HBV的易感宿主只局限于人以及黑猩猩等灵长类动物,HBV感染性疾病的研究遇到很大困难。多种小动物研究模型的建立,使我们对HBV感染致病机制的认识有了很大进步,包括:分子病毒学特征、在感染细胞中生命周期、机体的抗病毒免疫反应、肝脏病变的免疫病理机制等。但是,由于已有动物模型的种种限制,我们对HBV感染及乙型肝炎发生和发展的认识还远远不够,目前除了抗病毒治疗外,还没有有效地治疗慢性乙肝的方法。建立能够真实反映临床HBV感染、乙肝发生和进展过程的纯系小鼠模型,对于我们全面深入地理解HBV感染的侵入机制、宿主和病毒之间相互作用,以及发展预防和治疗HBV感染的新方法都具有非常重要的意义。     

Isolation,cloning and transgenic expression of hepatitis B surface antigen (HBsAg) in Solanum lycopersicum L

The Hepatitis B virus (HBV) infection is one of the most widespread viral infections of humans. HBV causes acute and chronic hepatitis. Chronic hepatitis leads to hepatocellular carcinoma, which is a significant cause of death. DNA-based immunization programs to control the spread of Hepatitis B in developing countries are costly and require special storage and transportation. The alternative way is to express Hepatitis B surface antigen (HBsAg) in plants to develop oral vaccines. In this study, HBsAg gene was isolated, cloned, and then transformed in tomato plants. The transgenic tomato plants were confirmed through RT-qPCR. HBsAg expression was analysed in mature green and red stages of tomato fruit through quantitative real-time PCR. It was observed that expression of HBsAg was high in matured red tomato as compared to mature green. The present study is the first step to developing Solanum lycopersicum as an edible vaccine production system in this world region.     

Human low-density lipoprotein receptor plays an important role in hepatitis B virus infection

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV vaccine is effective to prevent new HBV infection but does not offer therapeutic benefit to hepatitis B patients. Neither are current antiviral drugs curative of chronic hepatitis B. A more thorough understanding of HBV infection and replication holds a great promise for identification of novel antiviral drugs and design of optimal strategies towards the ultimate elimination of chronic hepatitis B. Recently, we have developed a robust HBV cell culture system and discovered that human apolipoprotein E (apoE) is enriched on the HBV envelope and promotes HBV infection and production. In the present study, we have determined the role of the low-density lipoprotein receptor (LDLR) in HBV infection. A LDLR-blocking monoclonal antibody potently inhibited HBV infection in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) as well as in primary human hepatocytes. More importantly, small interfering RNAs (siRNAs)-mediated knockdown of LDLR expression and the CRISPR/Cas9-induced knockout of the LDLR gene markedly reduced HBV infection. A recombinant LDLR protein could block heparin-mediated apoE pulldown, suggesting that LDLR may act as an HBV cell attachment receptor via binding to the HBV-associated apoE. Collectively, these findings demonstrate that LDLR plays an important role in HBV infection probably by serving as a virus attachment receptor.     

Production of hepatitis B surface antigen in recombinant plant systems: an update

There is a growing interest to develop oral vaccines for infectious diseases, as it is the most convenient and effective way to attain mucosal immunity. Hepatitis B continues to be a major infectious disease in many developing countries despite the availability of recombinant vaccine. On a global scenario, Hepatitis B Virus infection is probably the single most prevalent cause of persistent viraemia in humans. There are about 350 million chronic carriers of HBV, which is about 5% of the total world population. It is estimated that 75-100 million of them will die of liver cirrhosis and/or hepatocellular carcinoma. Progress in plant genetic engineering has enabled the transfer of useful genes for desirable traits. The recent trend is to use this technique to exploit plants as biofactories for the production of therapeutic proteins including vaccines. Rapid progress has been made in this area to develop plant-based vaccines for hepatitis B. This review describes the expression, characterization, and immunogenicity studies of hepatitis B vaccines produced in recombinant plant systems and their implications for developing a plant-based vaccine.     

基因工程乙肝疫苗研究进展

乙肝病毒(hepatitisBvirus,HBV)为嗜肝病毒,全世界有超过3亿人受到乙肝病毒的感染。综述近年来乙肝疫苗的最新研究进展,并对乙肝疫苗的发展历程,应用中出现的问题,克服不应答及低应答的策略,乙肝疫苗的发展方向以及目前最新的DNA疫苗进行了阐述 。     

Modelling the epidemiology of hepatitis B in New Zealand

Hepatitis B is a vaccine preventable disease caused by the hepatitis B virus (HBV) that can induce potentially fatal liver damage. It has the second highest mortality rate of all vaccine preventable diseases in New Zealand. Vaccination against HBV was introduced in New Zealand in 1988, and the country is now categorised with overall low endemicity but with areas of both high and medium endemic levels. We present an SECIR compartmental mathematical model, with the population divided into age classes, for the transmission of HBV using local data on incidence of infection and vaccination coverage. We estimate the basic reproduction number, R₀, to be 1.53, and show that the vaccination campaign has substantially reduced this below one. However, a large number of carriers remain in the population acting as a source of infection.     

Modeling the transmission dynamics and control of hepatitis B virus in China

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV) and is a major global health problem. HBV is the most common serious viral infection and a leading cause of death in mainland China. Around 130 million people in China are carriers of HBV, almost a third of the people infected with HBV worldwide and about 10% of the general population in the country; among them 30 million are chronically infected. Every year, 300,000 people die from HBV-related diseases in China, accounting for 40-50% of HBV-related deaths worldwide. Despite an effective vaccination program for newborn babies since the 1990s, which has reduced chronic HBV infection in children, the incidence of hepatitis B is still increasing in China. We propose a mathematical model to understand the transmission dynamics and prevalence of HBV infection in China. Based on the data reported by the Ministry of Health of China, the model provides an approximate estimate of the basic reproduction number R₀=2.406. This indicates that hepatitis B is endemic in China and is approaching its equilibrium with the current immunization program and control measures. Although China made a great progress in increasing coverage among infants with hepatitis B vaccine, it has a long and hard battle to fight in order to significantly reduce the incidence and eventually eradicate the virus.     

Immunosuppressive Drugs Modulate the Replication of Hepatitis B Virus (HBV) in a Hydrodynamic Injection Mouse Model

Hepatitis B virus (HBV) reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.