乙型肝炎：新的治疗方法可能有助于治愈慢性乙型肝炎

StephenW

News Release 3-Feb-2020
Hepatitis B: New therapeutic approach may help to cure chronic hepatitis B infection

Helmholtz Zentrum München - German Research Center for Environmental Health
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IMAGE: Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B.... view more

Credit: Helmholtz Zentrum München

Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B. The scientists found that the large amount of hepatitis B virus proteins expressed in the liver prevents the body's immune system to defeat the virus, consequently preventing an effective therapy. The researchers were able to show that knocking down the expression of the virus' proteins enables successful vaccination with TherVacB, a novel therapeutic vaccine.

Around 260 million humans, more than three percent of the world's population, are chronically infected by the hepatitis B virus. As a result, every year, 880,000 people worldwide die of liver failure or hepatocellular carcinoma. Currently no curative therapy is available. The therapies available to date inhibit virus replication, but need to be given long-term. As long as infected people cannot form an adequate immune response, the virus will survive. This is precisely where Prof. Ulrike Protzer, head of the Institute of Virology at Helmholtz Zentrum München and TUM, and her team start.

Novel therapeutic approach

Using a preclinical mouse model, the researchers found that proteins of the hepatitis B virus prevent that certain immune cells of the body, so-called CD8+ T-cells become effective. Based on these finding, the scientists developed a novel therapeutic approach: first, the expression levels of the virus proteins are knocked down, and then the immune cells are activated by therapeutic vaccination. In contrast to conventional vaccinations, which aim to prevent diseases before outbreak, such a therapeutic vaccination aims to cure already existing chronic diseases.

Successful suppression of virus proteins in mice

Consequently, the researchers first developed a method to suppress the hepatitis B virus proteins. They used siRNAs, small ribonucleic acid molecules that bind to the messenger RNA of the virus' proteins. By labelling the messenger RNA with siRNA, the infected cell receives the signal that the viral RNA is undesired and removes it. In this way protein expression is knocked down. However, the suppression of protein expression alone was not sufficient to reverse the inhibition of the CD8+ T-cells in chronically infected mice.

Infection cured in mice

The scientists therefore had to go one step further: "We then combined the siRNA method with a therapeutic vaccination developed by us. This enabled us to trigger a strong immune response against the virus. This led to cure of hepatitis B virus infection in two different mouse models," explains Dr. Thomas Michler, physician and one of the two first authors of the study.

Novel therapeutic vaccination soon in a clinical trial

The newly developed vaccine, called TherVacB, will be tested as an immunotherapy in a two-year clinical trial starting in 2021. "The therapeutic vaccine we have developed is indeed very promising as it induces neutralizing antibodies and T-cell responses," said Dr. Anna Kosinska, the other first author of the study. The vaccine will be administered in three doses every four weeks. It has been designed to target the majority of all hepatitis B viruses and therefore will be beneficial to most people infected worldwide.

"We are very pleased that for the clinical trials of TherVacB we are able to cooperate with a consortium of Europe's leading virologists, immunologists and hepatologist, guided by Helmholtz Zentrum München," adds Protzer. The consortium will receive funding of more than € 10 million from the European Union within the program Horizon 2020 (H2020-SC1-2019).

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Original publication

T. Michler et al., 2020: Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-titer HBV Carrier Mice. Gastroenterology, DOI: 10.1053/j.gastro.2020.01.032.

StephenW

新闻稿2020年2月3日
乙型肝炎：新的治疗方法可能有助于治愈慢性乙型肝炎

Helmholtz ZentrumMünchen-德国环境卫生研究中心
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图像：慕尼黑工业大学（TUM）的Helmholtz ZentrumMünchen和德国感染研究中心（DZIF）的研究人员已经开发出一种新型的治疗慢性乙型肝炎的治疗方法。...查看更多

图片来源：Helmholtz ZentrumMünchen

慕尼黑工业大学（TUM）的Helmholtz ZentrumMünchen和德国感染研究中心（DZIF）的研究人员已经开发出一种新型的治疗慢性乙型肝炎的治疗方法。科学家们发现，肝脏阻止了人体的免疫系统抵抗病毒，从而阻止了有效的治疗。研究人员能够证明，降低病毒蛋白的表达可以成功地使用新型治疗性疫苗TherVacB进行疫苗接种。

约有2.6亿人口，占世界人口的百分之三以上，长期受到乙型肝炎病毒的感染。结果，全世界每年有880,000人死于肝功能衰竭或肝细胞癌。目前尚无治疗方法。迄今为止可用的疗法抑制病毒复制，但是需要长期使用。只要感染者无法形成足够的免疫反应，病毒就可以存活。这正是Helmholtz ZentrumMünchen和TUM病毒研究所所长Ulrike Protzer教授及其团队的起点。

新颖的治疗方法

研究人员使用临床前的小鼠模型发现，乙型肝炎病毒的蛋白质阻止了人体的某些免疫细胞，即所谓的CD8 + T细胞发挥作用。基于这些发现，科学家们开发了一种新颖的治疗方法：首先，降低病毒蛋白的表达水平，然后通过治疗性疫苗激活免疫细胞。与旨在预防暴发前疾病的常规疫苗接种相反，这种治疗性疫苗接种旨在治愈已经存在的慢性疾病。

成功抑制小鼠中的病毒蛋白

因此，研究人员首先开发了一种抑制乙型肝炎病毒蛋白的方法。他们使用了siRNA，一种小核糖核酸分子，与病毒蛋白质的信使RNA结合。通过用siRNA标记信使RNA，被感染的细胞会收到不需要病毒RNA的信号并将其去除。这样，蛋白质表达被敲低。但是，仅抑制蛋白质表达不足以逆转慢性感染小鼠中CD8 + T细胞的抑制作用。

小鼠感染治愈

因此，科学家们必须进一步采取行动：“然后，我们将siRNA方法与我们开发的治疗性疫苗相结合。这使我们能够引发针对该病毒的强大免疫反应。这导致了两种不同的治愈乙型肝炎病毒感染的方法老鼠模型”，该研究的两位第一作者之一，医师Thomas Michler博士解释说。

新的治疗性疫苗即将在临床试验中

新开发的名为TherVacB的疫苗将从2021年开始在一项为期两年的临床试验中作为免疫疗法进行测试。“我们开发的治疗性疫苗确实非常有希望，因为它可以诱导中和抗体和T细胞反应。”该研究的另一第一作者安娜·科辛斯卡（Anna Kosinska）。疫苗每四周分三剂给药。它旨在针对所有乙型肝炎病毒中的大多数，因此将对全世界大多数感染者有益。

Protzer补充说：“对于TherVacB的临床试验，我们能够与由Helmholtz ZentrumMünchen指导的欧洲领先的病毒学家，免疫学家和肝病学家组成的联盟合作，我们感到非常高兴。”该联盟将在Horizo​​n 2020（H2020-SC1-2019）计划中从欧盟获得超过1000万欧元的资金。

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原始出版物

T. Michler等人，2020年：击倒病毒抗原表达可提高高滴度HBV携带者小鼠的治疗性疫苗效力。胃肠病学，DOI：10.1053 / j.gastro.2020.01.032。

齐欢畅

灵魂不屈

感谢分享！要到2021年才能进入临床。

hbv_challenger

备注 好帖 希望有好的临床结果！！！！！！

snowxyxy

“the researchers found that proteins of the hepatitis B virus prevent that certain immune cells of the body, so-called CD8+ T-cells become effective.” 赞