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PreS1 评估对慢性乙型肝炎病毒感染管理的影响。

Impact of preS1 Evaluation in the Management of Chronic Hepatitis B Virus Infection.

机构信息

Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

出版信息

Medicina (Kaunas). 2024 Aug 16;60(8):1334. doi: 10.3390/medicina60081334.

DOI:10.3390/medicina60081334
PMID:39202615
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11356368/
Abstract

: The measurement of hepatitis B surface antigen (HBsAg) is essential for managing chronic hepatitis B virus infection (CHB). HBsAg consists of three different surface envelope proteins: large, middle, and small HB surface proteins. However, in clinical practice, it is not common to evaluate each of these HB surface proteins separately. : In this study, we investigated preS1 expression using seven monoclonal antibodies (mAbs) in 68 CHB patients, as well as examining their antigenicity. : Although the seven mAbs had been derived from genotype (Gt) C, they could recognize preS1 with Gts A to D. The epitopes were concentrated within the aa33-47 region of preS1, and their antigenicity was significantly reduced by an aa45F substitution. We found that preS1 expression remained consistent regardless of HBsAg levels and different Gts in CHB patients, in contrast to what was observed in SHBs. : These results suggest that the antigenic epitope is preserved among different Gts and that the expression pattern of preS1 is altered during CHB, highlighting its vital role in the HBV infection cycle. Our present results suggest preS1 is a promising therapeutic target in CHB.

摘要

乙肝表面抗原（HBsAg）的测量对于慢性乙型肝炎病毒感染（CHB）的管理至关重要。HBsAg 由三种不同的表面包膜蛋白组成：大、中、小乙肝表面蛋白。然而，在临床实践中，通常不会分别评估这些 HB 表面蛋白中的每一种。

在这项研究中，我们使用七种单克隆抗体（mAbs）在 68 名 CHB 患者中研究了前 S1 的表达，并检查了它们的抗原性。

尽管这七种 mAbs 源自基因型（Gt）C，但它们可以识别 Gts A 到 D 的前 S1。表位集中在前 S1 的 aa33-47 区域内，aa45F 取代会显著降低其抗原性。我们发现，与 SHBs 不同，CHB 患者的前 S1 表达不受 HBsAg 水平和不同 Gts 的影响，保持一致。

这些结果表明，抗原表位在不同 Gts 之间得以保留，并且前 S1 的表达模式在 CHB 期间发生改变，突出了其在 HBV 感染周期中的重要作用。我们目前的结果表明，前 S1 是 CHB 有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/69f829448f99/medicina-60-01334-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/cc5c6866f846/medicina-60-01334-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/55ad7126c0a1/medicina-60-01334-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/23b66007f8af/medicina-60-01334-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/b8ac1e7c40e6/medicina-60-01334-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/af5822f42d0a/medicina-60-01334-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/69f829448f99/medicina-60-01334-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/cc5c6866f846/medicina-60-01334-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/55ad7126c0a1/medicina-60-01334-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/23b66007f8af/medicina-60-01334-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/b8ac1e7c40e6/medicina-60-01334-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/af5822f42d0a/medicina-60-01334-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbc5/11356368/69f829448f99/medicina-60-01334-g006.jpg

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本文引用的文献

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Hepatitis B Surface Antigen Isoforms: Their Clinical Implications, Utilisation in Diagnosis, Prevention and New Antiviral Strategies.乙肝表面抗原亚型：它们的临床意义、在诊断、预防中的应用及新的抗病毒策略
Pathogens. 2024 Jan 3;13(1):46. doi: 10.3390/pathogens13010046.
2
Hybrid large hepatitis B surface protein composed of two viral genotypes C and D induces strongly cross-neutralizing antibodies.由两种病毒基因亚型C和D组成的混合型大乙肝表面蛋白可诱导产生强效交叉中和抗体。
Vaccine. 2023 Oct 13;41(43):6514-6521. doi: 10.1016/j.vaccine.2023.09.026. Epub 2023 Sep 20.
3
Development of monoclonal antibodies to target the large surface protein of hepatitis B virus and their use in therapeutic and diagnostic applications.
针对乙型肝炎病毒大表面蛋白的单克隆抗体的研发及其在治疗和诊断应用中的用途。
J Viral Hepat. 2023 Nov;30(11):870-878. doi: 10.1111/jvh.13880. Epub 2023 Jul 31.
4
The persistence of seroprotective levels of antibodies after vaccination with PreHevbrio, a 3-antigen hepatitis B vaccine.接种 PreHevbrio（一种三抗原乙型肝炎疫苗）后，抗体仍保持在保护水平以上。
Vaccine. 2023 Jun 1;41(24):3584-3588. doi: 10.1016/j.vaccine.2023.05.010. Epub 2023 May 11.
5
PreS1 Containing HBc VLPs for the Development of a Combined Therapeutic/Prophylactic Hepatitis B Vaccine.用于开发联合治疗性/预防性乙型肝炎疫苗的含前S1核心蛋白病毒样颗粒
Microorganisms. 2023 Apr 8;11(4):972. doi: 10.3390/microorganisms11040972.
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Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus.乙型肝炎和丁型肝炎病毒：免疫重点的综合更新。
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