瑞典研究人员开发慢性乙型和丁型肝炎感染的新疗法

StephenW

瑞典研究人员开发慢性乙型和丁型肝炎感染的新疗法
吉姆·康纳尔
2022 年 8 月 26 日 - 3 分钟
照片/Shutterstock

一种新的针对乙型和丁型肝炎病毒的免疫疗法，这两种病毒都可能导致肝癌，在动物模型中显示出有希望的结果。

瑞典卡罗林斯卡学院的研究人员正在开发的治疗结果已发表在《肠道》杂志上。

乙型肝炎病毒 (HBV) 和丁型肝炎病毒 (HDV) 的慢性感染是导致严重肝损伤和肝癌的主要原因。

存在针对乙型肝炎的疫苗，但目前有超过 2.5 亿人患有慢性感染。可用的治疗很少导致感染完全消失，这意味着肝损伤的风险仍然存在。目前对慢性丁型肝炎感染的治疗只能治愈大约四分之一的患者。

现在，瑞典卡罗林斯卡学院的研究人员正在开发一种新型治疗方法，他们希望能够对这两种病毒产生持久的治疗反应。
治疗细节

该治疗包括两个组件，旨在以不同的方式影响免疫系统。首先，施用基于 DNA 的疫苗，激活针对这两种病毒的中和抗体和 T 细胞的产生。然后，给予重复剂量的基于蛋白质的疫苗以加强免疫系统的激活。

研究表明，这种治疗可以保护培养的细胞免受 HBV 和 HDV 感染。当对携带部分乙型和丁型肝炎病毒（类似于慢性HBV感染）的小鼠进行治疗时，这些动物会产生高水平的所需抗体和T细胞。

此外，来自治疗小鼠的抗体能够保护携带人类肝细胞的小鼠免受HBV和HDV的同时感染。此外，这些抗体能够保护患有慢性HBV感染的小鼠免受HDV感染。这一点特别重要，因为慢性 HBV 感染患者如果感染 HDV，就有患上严重疾病的风险。
有希望的结果

“这些都是有希望的结果，”卡罗林斯卡学院检验医学系教授、该研究的两位主要作者之一马蒂·塞尔伯格说。

“研究表明这是一条可行的途径，并鼓励我们继续开发这种用于人类的治疗方法。我们现在正在优化基于蛋白质的部分，以实现符合制药标准的大规模生产，然后进行最终的安全性研究，然后才能申请我们的第一项人体研究。”

该疗法是在瑞典卡罗林斯卡学院的检验医学系开发的。细胞培养试验是与德国海德堡大学合作完成的，携带人类肝细胞的小鼠实验是与比利时根特大学合作完成的。

该研究由瑞典癌症协会、瑞典研究委员会、Vinnova、CIMED、Horizo​​n 2020 和斯德哥尔摩地区的 ALF 基金资助。

StephenW

Swedish researchers developing new treatment for chronic hepatitis B and D infections
By Jim Cornall
August 26, 2022 - 3 minutes
Photo/Shutterstock

A new immunological treatment against hepatitis B and D viruses, both of which can cause liver cancer, shows promising results in animal models.

Results from the treatment, which is being developed by researchers at Karolinska Institutet in Sweden, have been published in the journal Gut.

Chronic infections of the hepatitis B virus (HBV) and hepatitis D virus (HDV) are major causes of severe liver damage and liver cancer.

A vaccine against hepatitis B exists, but more than 250 million people currently have chronic infections. The available treatment rarely leads to the complete disappearance of the infection, which means that the risk of liver damage remains. Current treatment for chronic hepatitis D infection only cures about a quarter of patients.

Now, researchers at Karolinska Institutet in Sweden are developing a new type of treatment they hope will provide a lasting treatment response against both viruses.
Treatment details

The treatment consists of two components designed to affect the immune system in different ways. First, a DNA-based vaccine is administered that activates the production of neutralizing antibodies and T-cells against both viruses. Then, repeated doses of a protein-based vaccine are given to reinforce the activation of the immune system.

The study shows the treatment can protect cultured cells against HBV and HDV infection. When the treatment was given to mice carrying parts of the hepatitis B and D virus, which resembles a chronic HBV infection, the animals produced the desired antibodies and T-cells at high levels.

Furthermore, antibodies from treated mice were able to protect mice carrying human liver cells against simultaneous infection with HBV and HDV. In addition, these antibodies were able to protect mice with chronic HBV infection against HDV infection. This is of particular importance because patients with chronic HBV infection are at risk of serious illness if infected with HDV.
Promising results

“These are promising results,” said Matti Sällberg, professor at the Department of Laboratory Medicine at Karolinska Institutet and one of the study’s two lead authors.

“The study shows this is a viable route and encourages us to continue developing this treatment for use in humans. We are now optimizing the protein-based part to enable large-scale production to pharmaceutical standards, and then doing the final safety studies before we can apply for our first study with human subjects.”

The treatment was developed at the Department of Laboratory Medicine at Karolinska Institutet in Sweden. The tests in cell culture were done in collaboration with Heidelberg University in Germany and the experiments in mice carrying human liver cells were done in collaboration with Ghent University in Belgium.

The research was funded by the Swedish Cancer Society, the Swedish Research Council, Vinnova, CIMED, Horizon 2020 and ALF funds from the Stockholm Region.