A new study to combat chronic hepatitis B

A new study to combat chronic hepatitis B

Publication date: 22-02-2024

Updated on: 21-05-2024

Topic: Research

Estimated reading time: 1 min

Over 300 million people worldwide are affected by the chronic form of hepatitis B, one of the leading risk factors for liver cirrhosis and liver cancer. In patients with this chronic infection, the immune system fails to eradicate the virus responsible for the disease, which continues to survive and reproduce within liver cells. A group of researchers from Vita-Salute San Raffaele University, through close collaboration with the American start-up Asher Biotherapeutics, has tested a molecule capable of reactivating the immune system against chronic hepatitis B for the first time in the world in preclinical models.

The findings published today in the prestigious scientific journal Science Translational Medicine lay the groundwork for the development in the clinic of an immunotherapy for this serious disease. 

The study was coordinated by Professor Matteo Iannacone, director of the Division of Immunology, Transplantation and Infectious Diseases at San Raffaele Research Hospital, who returned to Italy after a long research experience in the United States, supported by a Career Development Award from the Armenise-Harvard Foundation.

乙型肝炎病毒和当前疗法

乙型肝炎病毒(HBV)的传播途径包括:

  • 通过接触受感染的血液;
  • 通过性途径;
  • 分娩时母婴传播。

与成人感染病毒不同的是,90% 以上出生时感染病毒的婴儿会发展为慢性乙型肝炎。

慢性感染患者的免疫系统无法清除致病病毒,病毒会继续在肝细胞内存活和繁殖。

目前有一种预防该疾病的疫苗,但受感染的患者无法从中受益。抗病毒药物领域的科学研究正在取得重大进展,圣拉斐尔科学研究医院是该领域的国际标杆。

Matteo Iannacone 医生的研究小组与圣拉斐尔研究所副科学主任 Luca Guidotti 医生领导的研究小组密切合作,近年来为开发出目前常用的一些治疗慢性病的抗病毒药物做出了贡献。

如何唤醒免疫系统:圣拉斐尔科学研究医院的建议

为什么免疫系统仍然无效,如何才能唤醒它?科学家们在 2019 年发表于《自然》(Nature)的一项研究中已经解决了这一问题。研究人员通过使用显微镜内观察技术进行分子分析,证明了T淋巴细胞(免疫系统中负责攻击HBV病毒的细胞)从被激活的那一刻起,就无法根除感染并出现功能障碍。 

对功能失调的 T 淋巴细胞进行定性的工作也使圣拉斐尔的研究人员能够确定更适合和更有效唤醒这些细胞的分子。其中包括白介素-2,这是一种免疫系统的分子信使,可作为一种免疫疗法,已在从患者样本中获得的培养细胞和动物模型中成功进行了测试。

遗憾的是,白细胞介素-2 在全身使用时会产生严重的副作用:它会增加血管的通透性,导致严重的水肿。出现这种情况的原因是,白细胞介素-2 分子不仅能到达其目标 T 淋巴细胞,而且还能作用于自然杀伤细胞,而自然杀伤细胞会诱发毒性,此外还能作用于抑制免疫反应的调节细胞。

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