阻止乙型和丁型肝炎病毒进入肝细胞作为一种新型的免疫疗

StephenW

Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections
Panagiota Maravelia, Lars Frelin, Yi Ni, Noelia Caro Pérez, Gustaf Ahlén, Neetu Jagya, Georg Verch, Lieven Verhoye, Lena Pater, Magnus Johansson, Anna Pasetto, Philip Meuleman, Stephan Urban, Matti Sällberg
The Journal of Infectious Diseases, Volume 223, Issue 1, 1 January 2021, Pages 128–138, https://doi.org/10.1093/infdis/jiaa036
Published:
29 January 2020
Article history

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Abstract
Background

Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry.
Methods

Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes.
Results

The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice.
Conclusions

We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.
chronic hepatitis B, immunotherapy, PreS1 antibodies, T-cell tolerance, hepatitis D antigen

StephenW

阻止乙型和丁型肝炎病毒进入肝细胞作为一种新型的免疫疗法来治疗慢性感染。
Panagiota Maravelia，Lars Frelin，伊妮，Noelia CaroPérez，GustafAhlén，Neetu Jagya，Georg Verch，Lieven Verhoye，Lena Pater，Magnus Johansson，Anna Pasetto，Philip Meuleman，Stephan Urban，MattiSäberg
《传染病杂志》，第223卷，第1期，2021年1月1日，第128–138页，https：//doi.org/10.1093/infdis/jiaa036
发布时间：
2020年1月29日
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抽象
背景

慢性乙型和丁型肝炎病毒（HBV / HDV）感染可导致癌症。当前使用核苷类似物（NAs）的HBV治疗是终生的，可以减少但不能消除罹患癌症的风险。慢性乙型肝炎的标志是功能异常的HBV特异性T细胞反应。因此，我们设计了一种由针对HDV抗原（HDAg）的幼稚健康T细胞驱动的免疫疗法，以绕过对HBV特异性T细胞的需求，从而引发PreS1特异性T细胞和阻止HBV进入的PreS1抗体。
方法

评价了PreS1和/或HDAg序列的十种组合在体外和体内对PreS1抗体以及HBV和HDV特异性T细胞的诱导。在细胞培养中评估了PreS1特异性鼠和兔抗体对HBV的中和作用，并测试了兔抗PreS1在人类肝细胞再填充小鼠中的HBV中和作用。
结果

最好的候选疫苗可诱导T细胞针对PreS1和HDAg，以及PreS1抗体在体外阻断HBV进入。重要的是，在人源化小鼠中进行后续攻击后，PreS1抗体的过继转移可预防或调节HBV感染。
结论

我们在此描述了一种针对慢性HBV / HDV的新型免疫疗法，其靶向病毒进入以补充NAs和即将到来的抑制病毒成熟的疗法。
慢性乙型肝炎，免疫疗法，PreS1抗体，T细胞耐受性，D型肝炎抗原

StephenW

https://academic.oup.com/jid/article/223/1/128/5717223