A Phase I/IIa, Open-label, Randomised, Controlled, Multi-country, Dose-escalation Study to Assess the Safety and Immunogenicity of AS37 in Combination With the Hepatitis B Surface Antigen (HBsAg), According to a 0-1 Month Schedule, in Healthy, HBs naïve, Adults Aged 18-45 Years

This study is conducted to assess safety and immunogenicity of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system in healthy, HBs naïve, adults aged 18-45 years and to differentiate GSK's AS37 adjuvant system from other approved adjuvant systems and from an aluminum-based adjuvant.

开始日期2022-10-04

申办/合作机构

GSK Plc

NCT03410953

/ Completed临床4期IIT

Vaccination Adjuved Against Hepatitis B in SNS Workers Typed as no Responders to Conventional Vaccines

Health workers with biological risk in their tasks, who have been vaccinated as non-responders to conventional vaccination against Hepatitis B. To provide Health workers-staff with an additional protection tool against hepatitis B infection. To evaluate the efficacy of the adjuvanted vaccine in healthy nonresponders to conventional hepatitis B vaccine.

开始日期2018-04-13

申办/合作机构

Spanish Clinical Research Network

[+1]

NCT03459521

/ CompletedN/AIIT

Efficacy of Hepatitis B Virus Vaccines HBVaxpro40© and Fendrix© in Patients With Chronic Liver Disease in Clinical Practice.

Background: Cirrhotic patients have an increased risk of infections. In these patients is important to prevent hepatitis B virus (HBV) infection, as it may cause a deterioration of liver function. However, HBV vaccine efficacy in this group of patients is lower than in healthy population. Despite increasing standard doses to double doses or administering an accelerated pattern, the response to HBV vaccination remains suboptimal. For this reason, an alternative strategy may be using vaccines with novel adjuvants such as Fendrix® or the recombinant vaccine HBVAXPRO®.
Aim: To assess the adjuvanted HBV vaccine (Fendrix ®) efficacy in patients with chronic liver disease and to understand the kinetics of anti-HBs titers over time in patients who respond to vaccination.
Methods: Prospective and multicenter study. Serological markers of HBV will be assessed prospectively in consecutive patients with non-cirrhotic liver disease (permanent abnormal liver blood tests > six months; elastogram ≥8 kilopascal (kPa); serum markers of fibrosis (APRI or FIB-4 ≥ F2); ultrasound changes suggesting chronic liver disease) and cirrhotic patients (diagnosed by liver biopsy and/or non-invasive methods: clinical, blood tests and ultrasound). Seronegative patients will receive four doses of Fendrix ® at 0,1, 2 and 6 months. Antibodies against HBV superficial antigen (anti-HBs) will be determined at 2 months +/- 10 days, six months and one year after having received the fourth dose of the vaccine (to see kinetics). The study will differentiate between responders and non-responders to the vaccine: adequate immunity to HBV will be defined as anti-HBs higher than > 10mUI/mL (standard definition of seroconversion) and> 100mUI/mL. Investigators will evaluate the factors that influence the response, kinetics and safety of the vaccination in patients with chronic liver disease and cirrhosis.

开始日期2017-09-01

申办/合作机构

Corporacion Sanitaria Parc Tauli

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100 项与 Hepatitis B (rDNA) vaccine(GlaxoSmithKline Plc) 相关的专利（医药）

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项与 Hepatitis B (rDNA) vaccine(GlaxoSmithKline Plc) 相关的文献（医药）

2025-12-01·OCCUPATIONAL MEDICINE-OXFORD

Management of non-response to Hepatitis B re-vaccination

Article

作者: Giri, Prosenjit ; Kroening, Helen L ; Adisesh, Anil

Abstract:

Background:

Bloodborne viruses, including Hepatitis B (HBV), are a known occupational hazard for healthcare workers (HCWs), particularly those involved in exposure-prone procedures. Whilst standard vaccines can provide immunity, 5–10% of people remain non-responders (anti-HBs titre <10IU/L) despite repeated vaccinations. Fendrix® (HBV recombinant DNA vaccine) has been shown to be highly effective in renal patients and those with human immunodeficiency virus, implying it may also have benefits for healthy non-responders.

Aims:

Our analysis set out to identify and compare response rates to re-vaccination (with Fendrix® or HBvaxPro40®) in HCWs with non-response to standard vaccination procedures.

Methods:

Between 1 March 2010 and 30 April 2024, either Fendrix® or HBvaxPro40® was offered to HCWs with inadequate response to two courses of Engerix B® standard vaccination. Antibody tests were performed 6 weeks post-final vaccine dose. Serological results from this period were retrospectively statistically analysed to compare differential vaccine responses.

Results:

Eighty-five HCWs were identified as non-responders and offered further vaccination (42 received Fendrix® and 43 received HBvaxPro40®). Fendrix® resulted in a seroconversion rate of 95% (40/42) compared to 72% (31/43) with HBvaxPro40®; a significantly higher number responded more strongly to Fendrix® (74% versus 23%).

Conclusions:

Our results demonstrate the rationale for offering additional vaccination with Fendrix® to HCWs when standard vaccination and repeated administration has not elicited an adequate immune response. Multi-centre evaluation of this vaccination strategy for non-responder HCWs should be considered to generate evidence for the most acceptable and efficacious approach.

2024-07-31·Science Translational Medicine

Functional and epigenetic changes in monocytes from adults immunized with an AS01-adjuvanted vaccine

Article

作者: Smolen, Kinga K. ; Burny, Wivine ; Marchant, Arnaud ; Willems, Fabienne ; de Angelis, Simone P. ; Taton, Martin ; Bechtold, Viviane ; Didierlaurent, Arnaud M. ; Essaghir, Ahmed ; van der Most, Robbert ; Ndour, Cheikh ; Delandre, Simon

The adjuvant AS01 plays a key role in the immunogenicity of several approved human vaccines with demonstrated high efficacy. Its adjuvant effect relies on activation of the innate immune system. However, specific effects of AS01-adjuvanted vaccines on innate cell function and epigenetic remodeling, as described for Bacille Calmette-Guérin (BCG) and influenza vaccines, are still unknown. We assessed the long-term functional and epigenetic changes in circulating monocytes and dendritic cells induced by a model vaccine containing hepatitis B surface antigen and AS01 in healthy adults (NCT01777295). The AS01-adjuvanted vaccine, but not an Alum-adjuvanted vaccine, increased the number of circulating monocytes and their expression of human leukocyte antigen (HLA)–DR, which correlated with the magnitude of the memory CD4 + T cell response. Single-cell analyses revealed epigenetic alterations in monocyte and dendritic cell subsets, affecting accessibility of transcription factors involved in cell functions including activator protein-1 ( AP-1 ), GATA , C/EBP , and interferon regulatory factor. The functional changes were characterized by a reduced proinflammatory response to Toll-like receptor activation and an improved response to interferon-γ, a cytokine critical for the adjuvant’s mode of action. Epigenetic changes were most evident shortly after the second vaccine dose in CD14 + monocytes, for which accessibility differences of some transcription factors could persist for up to 6 months postvaccination. Together, we show that reprogramming of monocyte subsets occurs after vaccination with an AS01-adjuvanted vaccine, an effect that may contribute to the impact of vaccination beyond antigen-specific protection.

2024-05-01·The Lancet regional health. Western Pacific

Factors associated with hepatitis B vaccination in Laos: findings from the multiple indicator cluster surveys in 2011/12 and 2017

Article

作者: Black, Antony P ; Neven, Anouk ; Hefele, Lisa ; Hübschen, Judith M ; Essink, Dirk R ; Dekker, Trude

Background:

Within Laos, the vaccination coverage rates with the monovalent hepatitis B birth dose vaccine and hepatitis B antigen-containing combination vaccines remain stagnant with 75% and 64%, respectively, in 2021. In this study, we used data from the Multiple Indicator Cluster Surveys to identify possible factors that represent barriers for receiving these childhood vaccinations.

Methods:

Data from the Multiple Indicator Cluster Surveys in 2011/12 and 2017 were analysed to examine factors associated with receiving the hepatitis B-containing vaccines using regression modelling. Data analyses were conducted in R.

Findings:

In 2011/12, the weight-adjusted coverage rate for receiving the hepatitis B birth dose was 48%, while the coverage with the hepatitis B antigen-containing combination vaccine was 55.1% based on both vaccination documents and recall; compared to 69.3% and 59.4% respectively in 2017. Ethno-linguistic group, maternal education, healthcare utilization and wealth were associated with receiving the vaccinations against hepatitis B.

Interpretation:

National estimates of vaccination coverage rates can conceal country-specific regional or socio-economic variations. Children from Hmong-Mien households, from less wealthier households and whose mothers were less educated and were not able to or did not utilize healthcare were identified as being less likely to receive the vaccinations. These findings indicate the need for improving access to healthcare, in particular for minority groups.

Funding:

This work was supported by the Ministry of Foreign and European Affairs, Luxembourg and the Luxembourg Institute of Health (project "Luxembourg-Laos Partnership for Research and Capacity Building in Infectious Disease Surveillance").

项与 Hepatitis B (rDNA) vaccine(GlaxoSmithKline Plc) 相关的新闻（医药）

2026-02-14

·研日新

研日新 ·5| 02月15日重症医学科 | 普通外科 | 感染科

精选医学文献查看更多，请点击"阅读原文" 1. Selenomethionine as a dual-mechanism ferroptosis inhibitor: selenium-supply-driven GPX4 biosynthesis beyond transsulfuration and reductive-capacity-mediated ROS scavenging independent of GPX4 activity. [Acute Kidney Injury] Cell death & disease | 2026-02-13 | IF 8.1 AI硒代蛋氨酸通过双重机制抑制铁死亡，为顺铂肾毒性等铁死亡相关疾病提供了潜在的新型治疗策略。摘要Ferroptosis is an iron-dependent form of nonapoptotic cell death driven by lipid peroxidation. The selenium-dependent glutathione peroxidase 4 (GPX4) serves as the central regulator of ferroptosis through enzymatic reduction of phospholipid hydroperoxides (PLOOH). While GPX4 remains the canonical ferroptosis suppressor, whether alternative regulatory axes exist beyond this selenoprotein-mediated p... 阅读全部 2. IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury. [Acute Lung Injury] Cellular and molecular life sciences : CMLS | 2026-02-13 | IF 6.2 AI靶向IFIT3-USP18-STING轴可抑制M1巨噬细胞极化，为急性肺损伤早期抗炎治疗提供新策略。 3. A mixed-methods study investigating the acceptability of an early acceptance and commitment therapy (ACT) intervention to aid adjustment to appearance changes after burns. [Burns] Body image | 2026-02-13 | IF 5.2 AI早期接纳承诺疗法（ACT）干预（ProACTive）对烧伤患者具有可接受性，能有效降低情绪困扰，为临床早期心理支持提供了新选择。摘要Appearance concerns after burns start soon after injury. However, early psychological interventions to support individuals with their changed appearance are absent. This study investigated the acceptability of an early acceptance and commitment therapy (ACT) intervention delivered by a psychological therapist either in person or virtually to help individuals adjust to changes to their appearance a... 阅读全部 4. Preventing postoperative delirium. [Delirium] 社论 | BMJ (Clinical research ed.) | 2026-02-12 | IF 93.6 AI多模式综合干预措施能显著降低老年患者术后谵妄发生率，对改善手术预后具有重要临床价值。 5. Lactate derived from macrophages drives skin dermal fibroblasts phenotypic remodeling via MCT1-primed histone H3 lysine 23 lactylation in hypertrophic scar. [Burns] Nature communications | 2026-02-12 | IF 14.7 AI靶向MCT1-H3K23la-HEY2/COL11A1轴及其正反馈环路，为临床干预增生性瘢痕提供了新的精准治疗策略。摘要Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were ob... 阅读全部 6. Elovl6 inhibits colorectal cancer progression through stearic acid-mediated mitochondrial fusion and metabolic reprogramming. [Colorectal Neoplasms] Science advances | 2026-02-13 | IF 11.7 AIElovl6通过硬脂酸促进线粒体融合抑制CRC，为靶向脂代谢的精准治疗和饮食干预提供新策略。摘要Lipid metabolic reprogramming is a hallmark of colorectal cancer (CRC), yet the precise molecular mechanisms underlying lipid-mediated oncogenesis and the specific lipid metabolic enzymes involved remain largely elusive. Here, we identify elongation of very-long-chain fatty acid protein 6 (Elovl6) as a critical regulator in CRC progression. Clinical data reveal significant down-regulation of Elovl... 阅读全部 7. Helicobacter pylori and hyperglycemia fuel gastric cancer glycolysis: Mechanisms and targeted intervention (Review). [Stomach Neoplasms] 综述 | International journal of molecular medicine | 2026-02-13 | IF 5.7 AI临床医生可通过关注幽门螺杆菌感染和高血糖状态，识别胃癌糖酵解增强的高危患者，并考虑靶向糖酵解通路作为潜在的辅助治疗策略。摘要Helicobacter pylori (H. pylori) is a Gram‑negative bacterial pathogen, and infection with this pathogen is a primary risk factor for gastric cancer (GC), often inducing chronic gastritis, which further increases the risk of cancer. Glycolysis carries out a key role in GC metabolism, serving as the primary energy pathway for cancer cells, particularly under hypoxic conditions. Enhance... 阅读全部 8. Establishment of threshold of human gut microbes and risk assessment system for colorectal cancer. [Colorectal Neoplasms] Computers in biology and medicine | 2026-01-20 | IF 7.0 AI该研究首次建立了结直肠癌相关细菌的定量阈值，并开发了智能评估系统，为临床医生提供了基于肠道微生物的、高准确率的结直肠癌风险预测工具。摘要Being involved in the occurrence of colorectal cancer (CRC), gut microbes are potential targets for early diagnosis of CRC. Defining the threshold of these characteristic bacteria could provide a basis for the clinical application of microorganisms as novel tumor markers for CRC. To sort out and define the threshold of related bacteria and the ecological characteristics of gut bacteria. A total of... 阅读全部 9. Author Correction: Malaria trends in Ethiopian highlands track the 2000 'slowdown' in global warming. [Malaria] Published Erratum | Nature communications | 2026-02-13 | IF 14.7 AI临床医生应关注气候变化对疟疾流行趋势的影响，特别是在高海拔地区，这有助于优化预防策略和早期预警系统。 10. Corrigendum to "ubiquitin-like protein UBL5 and spliceosome associated factor SART1 jointly maintain the virulence in oxoplasma gondii" [Int. J. Biol. Macromol. 2025.149987]. [Zoonoses] Published Erratum | International journal of biological macromolecules | 2026-02-13 | IF 7.7 AI本研究揭示了UBL5与SART1协同调控弓形虫毒力的新机制，为开发针对弓形虫病的潜在治疗靶点提供了理论依据。 11. The incidence of spontaneous HBsAg loss in patients with different baseline HBsAg levels: a systematic review and meta-analysis. [Hepatitis B] Hepatology international | 2026-02-13 | IF 5.9 AI基线HBsAg水平是预测自发性清除的关键指标，低水平患者清除率显著更高，为临床决策提供重要参考。摘要Hepatitis B surface antigen (HBsAg) seroclearance is an ideal treatment end point in chronic hepatitis B (CHB), linked to improved clinical outcomes. Baseline HBsAg level is a key predictor, but pooled evidence on the annual incidence of spontaneous HBsAg clearance in untreated CHB patients, stratified by baseline HBsAg levels, is lacking. We conducted a systematic review and meta-analysis to quan... 阅读全部 12. An integrated green control strategy for plant viral co-infections: from multivalent vaccine construction to synergistically modified nanodelivery systems. [Coinfection] Journal of nanobiotechnology | 2026-02-11 | IF 10.6 AI该研究为临床医生提供了一种环境友好的植物病毒防控新策略，通过多价疫苗与纳米递送系统的结合，有望实现高效、安全的病害管理。摘要Plant viral co-infections pose a significant threat to global agricultural productivity. In this study, a novel multivalent attenuated vaccine (CMV-R2TP) was developed using the cucumber mosaic virus (CMV) as a backbone, together with a ROS-responsive vaccine nanodelivery system (pCMV-R2TP@PTP-TAT), offering a comprehensive and environmentally friendly strategy for managing plant viruses. Through ... 阅读全部 13. Identification of Compound 15 (MMV1581361) as a PfATP4 Inhibitor with Transmission-Blocking Activity and In Vivo Efficacy in a SCID Mouse Model of Malaria. [Malaria] Journal of medicinal chemistry | 2026-02-11 | IF 6.0 AI化合物15作为新型PfATP4抑制剂，在体外和动物模型中均显示出抗疟及传播阻断活性，为抗疟药物研发提供了有潜力的先导化合物，但其临床转化前景因耐药风险和竞争性候选药物而受限。摘要Focused structure-activity-relationship studies of MMV020136, 1, a whole-cell phenotypic screening hit originating from the Pathogen Box against the human malaria parasite, Plasmodium falciparum, led to the identification of compound 15 (MMV1581361). Compound 15 retained nanomolar activity against drug-sensitive, drug-resistant, and field isolates of Plasmodium falci... 阅读全部 14. Viscoelastic hydrogel primed CAR-macrophage for pulmonary fibrosis treatment. [Kidney Diseases] Nature communications | 2026-02-13 | IF 14.7 AI粘弹性水凝胶预处理通过机械调控CAR-M膜张力增强其抗纤维化疗效，为肺纤维化提供了一种非基因工程的增效新策略。摘要CAR-macrophage (CAR-M) therapy holds promise for the treatment of tumor and fibrotic diseases, yet genetic engineering remains the main efficacy-enhancing approach. Here we develop a non-genetic strategy using viscoelastic hydrogel to mechanically prime CAR-Ms. CAR-Ms exhibit potent phagocytosis of activated fibroblasts and collagen-degradation capacity, and hydrogel priming further enhances their... 阅读全部 15. MG53 mediates skeletal muscle-liver cross-talk and enhances alcohol metabolism in alcoholic liver disease. [Hypertension] Nature communications | 2026-02-13 | IF 14.7 AI靶向MG53-锌轴可增强酒精代谢并减轻肝损伤，为酒精性肝病提供新的治疗靶点。摘要Alcoholic liver disease (ALD) remains a significant clinical challenge with limited therapeutics. It is strongly associated with sarcopenia, which further worsens the prognosis in liver cirrhosis. Zinc-deficiency is a hallmark of ALD, impairing the liver's antioxidant defenses and alcohol metabolism. Here we identify a chaperone role for MG53/TRIM72 in facilitating crosstalk between zinc and alcoh... 阅读全部 16. Efficient pheromone navigation via antagonistic detectors in Caenorhabditis elegans male. [Stroke] Nature communications | 2026-02-13 | IF 14.7 AI理解这种拮抗感觉机制有助于开发针对神经退行性疾病或感觉处理障碍的新型神经调控策略。摘要Chemotaxis to a moving potential mate that emits a volatile sex pheromone poses a navigation challenge requiring rapid, precise responses to maximize reproductive success. Volatile chemicals form gradients that differ from soluble compounds, potentially making navigation based on comparisons between spatially separated sensors unreliable for small-bodied animals. Here we show that, rather than a s... 阅读全部 17. A neuron type-specific microexon in Ank3/ankyrin-G modulates calcium activity and neuronal excitability. [Stroke] Nature communications | 2026-02-13 | IF 14.7 AI该研究揭示了Ank3微外显子E35a通过调控钙信号影响神经元兴奋性，为理解双相情感障碍等神经精神疾病的病理机制提供了新的分子靶点。摘要Recent studies have revealed many alternative exons differentially spliced across diverse neuron types in the mammalian brain, but their links to neuronal physiology remain unclear. Here we characterize a deeply conserved microexon E35a in Ank3 encoding ankyrin-G (AnkG), a multifaceted adaptor protein best known as a master organizer of the axon initial segment (AIS) and as a leading genetic risk ... 阅读全部 18. Feeding decision-making by a single neuron via disparate neurotransmitters. [Deafness] Nature communications | 2026-02-13 | IF 14.7 AI该研究揭示了单个神经元通过不同神经递质双向调控摄食行为的机制，为理解进食障碍的神经基础提供了新视角。摘要Animals use gustatory information to decide whether to ingest nutritious substances or avoid toxic ones. Although certain neurons in the gustatory circuits respond to both aversive and appetitive signals, how these neurons resolve inputs with opposing valences is unknown. Here, we examine how the Drosophila melanogaster neuropeptide leucokinin (LK) affects gustatory information processing to elici... 阅读全部 19. Dual recruitment of two CCM2 molecules to KRIT1 suppresses KLF4 expression. [Stroke] Nature communications | 2026-02-13 | IF 14.7 AI该研究揭示了CCM2-KRIT1复合物调控KLF4表达的分子机制，为理解脑海绵状血管畸形的发病机理及开发靶向治疗策略提供了关键理论依据。摘要Regulated expression of Kruppel like factor (KLF) transcription factors is essential for normal maintenance of endothelial cells, but loss of either K-Rev interaction trapped 1 (KRIT1) or cerebral cavernous malformations 2 (CCM2) proteins results in significant over-expression of KLF4 protein, causing the cerebrovascular disorder, cerebral cavernous malformations. Here, combining knockdown and rec... 阅读全部 20. Comparing decentralized machine learning and AI clinical models to local and centralized alternatives: a systematic review. [COVID-19] NPJ digital medicine | 2026-02-13 | IF 12.4 AI对于临床医生而言，去中心化学习在隐私受限场景下提供了临床可接受的替代方案，其性能与中心化学习相当，但显著优于本地学习，有助于在遵守法规的同时实现高效诊断。摘要This systematic review evaluates how decentralized learning (DL) approaches-e.g., federated learning, swarm learning, ensemble-compare with traditional models in healthcare applications. We searched eight databases (01/2012 to 03/2024), screening 165,010 studies with two independent reviewers. Analysis included 160 articles comprising 710 DL models and 8149 performance comparisons across clinical ... 阅读全部免责声明：仅供学术交流参考，不构成任何医学建议或诊疗指导

临床结果临床研究

2026-01-30

·愚公生物

有望改写2.5亿慢性乙肝患者命运的ASO技术

愚公生物&百时美 ASO药物有望为乙肝治疗带来革命性突破近日，困扰人类数十年、被称为“沉默的肝脏杀手”的慢性乙肝，有望迎来首个6个月有限疗程的治疗方案。葛兰素史克（GSK）宣布其潜在“同类首创”药物 bepirovirsen 在乙肝治疗两项关键三期临床试验中取得积极结果，均达到了主要终点。这意味着，一种全新的、有望在有限疗程内实现慢性乙型肝炎“功能性治愈”（即停药后持续检测不到病毒）的药物离我们更近了一步。而这款明星药物的核心，正是一种名为“反义寡核苷酸”的前沿技术。 01 从“终生服药”到“有限疗程”：一个治疗范式的颠覆慢性乙型肝炎影响着全球超过2.5亿人，是导致肝癌的主要元凶。根据2024年公布的全国乙肝普查，我国乙肝病毒感染者数量目前仍有7500 万，占全球近三分之一。长期以来，患者通常需要终身服用核苷类似物药物来抑制病毒，但实现“功能性治愈”的比例极低，仅为1%左右。新型干扰素疗法的临床治愈率略高，但也需要多年持续用药，且副作用偏大。 bepirovirsen的三期临床成功，带来了颠覆性的希望。试验结果显示，其联合现有标准疗法，6个月内就在患者中实现了具有统计学和临床意义的功能性治愈率，尤其对基线乙肝表面抗原水平较低的患者效果更佳。这一切突破，都源于其作用机制的核心——反义寡核苷酸。 02 什么是反义寡核苷酸？——精准的基因“沉默术” ▶ 基本构成反义寡核苷酸(Antisense Oligonucleotides，ASOs)是一段人工合成的、短的单链DNA（多数情况）或RNA片段（通常12-30个核苷酸）。 ▶ 核心原理遵循碱基互补配对原则（就像DNA双链中的A配T，C配G），这段合成序列被设计成与细胞内特定的致病性信使RNA完全互补配对。 ▶ “反义”之名细胞中天然转录出的、用于指导蛋白质合成的RNA被称为“正义”链。而这段人工合成的、与之互补配对的序列，就被称为“反义”链。反义寡核苷酸（ASO）与靶向RNA结合。（a）RNA聚合酶从DNA模板转录RNA （b）天然转录得到的RNA（“正义”链）（c）合成的ASO（红色）通过碱基互补配对规则与靶向RNA（蓝色）结合。（d）合成的ASO（“反义” 链） 03 ASOs如何工作？——三大机制精准打击 ASOs进入细胞后，通过与靶标mRNA分子互补结合，调控基因表达，从而影响蛋白质的合成。主要通过以下几种方式发挥作用： ▶ 机制一：招募“剪刀”，降解mRNA（RNase H1依赖途径）这是bepirovirsen采用的核心机制之一。当ASOs与病毒mRNA结合形成DNA-RNA杂交双链时，会招募细胞内的“剪刀”——RNase H1酶。该酶会精准切割并降解病毒mRNA，使其无法继续作为模板生产病毒蛋白和新的病毒，从而从根源上抑制病毒复制。 ▶ 机制二：充当“导航”，修正剪接对于由基因剪接错误导致的疾病（如某些遗传病），ASO可以结合在pre-mRNA的错误剪接位点附近，阻止错误的剪接发生，同时促进正确的剪接，从而产生功能正常的蛋白质。 ▶ 机制三：物理“占位”，干扰翻译有些ASO经过特殊化学修饰，不激活RNase H1。它们结合到mRNA的起始密码子等关键位置后，通过简单的空间位阻效应，像一块石头堵住道路一样，阻止核糖体与mRNA结合，从而抑制蛋白质的翻译过程。反义寡核苷酸（ASO）的功能机制。ASOs与互补的mRNA分子结合，这种结合可以阻断翻译过程或促进mRNA的降解，从而降低目标蛋白的表达。以bepirovirsen为例，它作为一种三重机制的ASO药物，不仅能通过RNase H1途径降解乙肝病毒的RNA，降低血液中的病毒抗原水平，还能刺激人体免疫系统，帮助机体恢复对病毒的控制能力。 04 从概念到临床：ASO药物的发展简史 ASO的概念早在1978年就已提出，但其转化之路并非一帆风顺，主要挑战在于稳定性、递送效率和脱靶效应。随着化学修饰技术的突破（如硫代磷酸酯骨架、2'-MOE修饰等），ASO的稳定性和效力大大提升，终于迎来了开花结果的时期。目前，全球已有十余款ASO药物获批上市，用于治疗一些以往无法触及的疾病：脊髓性肌萎缩症：Spinraza®注射液，通过修正SMN2基因的剪接，成为该病的首个疾病修正治疗药物。遗传性转甲状腺素蛋白淀粉样变性：Tegsedi®，通过降解致病蛋白的mRNA来治疗。杜氏肌营养不良症：Exondys 51®，FDA批准的首个杜氏肌营养不良症新药。这些成功先例，为ASO技术在乙肝等重大传染病领域的应用铺平了道路。 05 未来展望：不止于乙肝的“精准医疗”利器 bepirovirsen的突破，只是ASO疗法广阔前景的冰山一角。它的优势在于： ▶ 设计精准可以针对任何已知序列的致病基因进行设计。 ▶ 作用直接在转录后水平进行干预，无需改变基因组DNA。 02 研发周期相对较短一旦靶点明确，药物设计和合成速度较快。目前，数百项ASO临床试验正在进行中，适应症涵盖肿瘤、心血管疾病、神经系统疾病、代谢性疾病等众多领域。随着递送技术的不断改进，ASO药物的应用范围正从肝脏扩展到全身多个组织器官。 ✦ 结语从应对罕见遗传病，到挑战像慢性乙肝这样困扰全球数亿人的重大公共卫生问题，反义寡核苷酸技术正在重新定义药物研发的边界。bepirovirsen的临床成功，不仅为乙肝患者带来了治愈的曙光，也再次证明了通过精准“沉默”致病基因来治疗疾病的巨大潜力。我们正步入一个由核酸药物引领的精准治疗新时代，未来，让我们共同期待，这场基因层面的医疗革命，能带来更多生命奇迹。温馨提示：本文为医学科普，仅供了解相关知识与信息。不构成任何医疗建议参考文献葛兰素史克-中国官网 https://www.gsk-china.com/zh-cn/media/press-releases/bepirovirsen-phase-iii-results/ WHO. Global hepatitis report 2024. (last accessed: January 2026) Rumgay H et al . Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77:1598–1606. Slaets, L. et al. “Systematic review with meta-analysis: hepatitis B surface antigen decline and seroclearance in chronic hepatitis B patients on nucleos(t)ide analogues or pegylated interferon therapy” in GastroHep 2, 106–116 (2020) Liu, M., Wang, Y., Zhang, Y. et al. Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines. Sig Transduct Target Ther 10, 73 (2025). Bennett CF. Therapeutic Antisense Oligonucleotides Are Coming of Age. Annu Rev Med. 2019;70:307-321. 往期阅读限制性内切酶在中国限制性内切酶的前世今生 Gibson无缝克隆，你所不知道的 🧬 探秘T4连接酶：基因“分子缝合针” 🧬 聊聊合成生物学（一）——什么是合成生物学聊聊合成生物学（二）——合成生物学的前世今生聊聊合成生物学（三）——20世纪推动合成生物学发展的大佬们关于我们江苏愚公生物科技有限公司（简称“愚公生物”）致力于解决国内合成生物学和生物医药上游原料酶的“卡脖子”现状，立志成为亚洲DNA/RNA工具酶产品种类最多的生产企业。公司总部位于中国（江苏）自贸区连云港片区，参照GMP标准建设与管理，已通过高新技术企业、省级“专精特新”中小企业、ISO13485质量管理体系认证；子公司江苏百时美生物科技有限公司位于连云港国家级高新区，主要承担原酶研究和科研试剂生产。秉承愚公移山的精神，愚公生物在国内首次实现了限制性内切酶的规模化生产，国产替代率超过10%。现拥有限制酶、基因扩增、逆转录、荧光定量PCR、修饰克隆、体外转录、速溶颗粒等11个系列上百种产品，进入国内大多数基因合成龙头企业的供应链。点击“阅读原文”，了解更多！

寡核苷酸信使RNA临床3期

2026-01-16

·医会宝消化肝病视界

中国「乙肝功能性治愈」的研发进展：5种疗法值得期待

慢性乙型肝炎（CHB）迄今仍是全球最为严峻的公共卫生挑战之一。目前全球乙型肝炎病毒（HBV）感染者约2.54亿例，我国感染者规模达7900万例。CHB功能性治愈率较低，随着疾病进展可逐步引发肝硬化，甚至进展为肝细胞癌。相关研究数据表明，CHB所致肝癌病例占比高达56%。不过，全球即将进行CHB功能性治愈的时代！官方披露，Bepirovirsen的两项全球多中心、随机、双盲、对照Ⅲ期临床试验（B-Well 1与B-Well 2）取得积极结果。该药物计划于2026年第一季度启动全球监管申报，申报范围覆盖包括中国在内的29个国家。除Bepirovirsen外，中国多款CHB功能性治愈候选药物正处于临床研发后期阶段，本文将对其进行系统汇总。图源：医会宝编辑部乙肝功能性治愈定义：乙型肝炎表面抗原（HBsAg）持续阴性（治疗后≥24周）、伴或不伴乙型肝炎表面抗体（HBsAb）血清学转化，且在有限治疗疗程后乙型肝炎e抗原（HBeAg）与血清HBV DNA均不可检测、肝功能恢复正常，且肝脏病理学和组织学得到改善[1]。 Part.1 AHB-137 AHB-137与Bepirovirsen一样，也是一种非偶联的反义寡核苷酸（ASO）药物。在两项Ⅱ（a+b）期临床研究中[2]，纳入了119例HBeAg阴性、稳定核苷（酸）类似物（NA）单药治疗、基线HBsAg>100-3000 IU/mL且HBV DNA<100 IU/mL的CHB参与者。在Ⅱa期研究中，参与者每周接受AHB-137（300mg或225mg）治疗，持续24周；在Ⅱb期研究中，参与者接受AHB-137 300mg治疗24周，或接受安慰剂治疗8周后，再接受AHB-137 300mg治疗16周。 AHB-137治疗结束后，参与者继续接受核苷单药治疗24周，之后进入24周的随访，期间根据NA停药标准决定维持或停用治疗（停药标准：HBsAg<0.05 IU/mL且HBV DNA<10 IU/mL）。结果显示，在接受300mg AHB-137治疗24周（第48周）的参与者中，26.6%（17/64例）在第48周实现了持续的完全应答。该应答率在不同基线HBsAg水平的亚组中具有可比性。在这些应答者中，82.4%（14/17例）的抗-HBs抗体滴度达到了≥10 IU/L。此外，29.7%（19/64例）的参与者达到了部分应答（即HBsAg≥0.05至<10 IU/mL且HBV DNA <10 IU/mL）。 A：根据2a期与2b期临床试验分组 B：根据基线HBsAg水平分组实现HBsAg清除或降至＜10 IU/mL的患者占比（图源：文献2）安全性方面，治疗期间出现的不良事件主要发生在AHB-137治疗期间。未报告与治疗相关的严重不良事件，也没有因不良事件导致治疗中止、提前停药或死亡的情况。 Part.2 GST-HG131 GST-HG131是全球首创的口服HBsAg抑制剂，它通过调节宿主PAPD5/7活性，抑制HBV mRNA的聚腺苷酸尾组装并使HBV mRNA去稳定化。临床前研究显示了强大的疗效和良好的安全性，在I期试验中也表现出良好的安全性、耐受性和药代动力学特征。一项双盲、随机、安慰剂对照的II期研究显示[3]，针对正在接受NA单药治疗超过6个月、HBsAg水平介于100至1500 IU/mL之间，血清ALT水平低于正常值上限的1倍的CHB患者，接受12周的30 mg每日两次方案的患者（n=25)，76.5% 的受试者达到了HBsAg<100 IU/mL，安慰剂相比，在第85天时平均HBsAg降低了0.89 log₁₀ IU/mL（p<0.001），最大降幅达1.64 log₁₀ IU/mL。在安全性方面，在所有队列中，治疗耐受性良好，未出现剂量相关毒性或新的安全信号。大多数不良事件为轻度或中度。在实验室检查、生命体征或心电图方面未观察到临床相关的异常。 Part.3 HT-101+HT-102 HT-101是一种靶向乙肝肝炎病毒（HBV）基因组S区的N-乙酰半乳糖胺（GalNAc）偶联小干扰核糖核酸（siRNA），在Ⅰ期研究中显示出对HBsAg的持久降低效果。 HT-102是一种针对HBsAg抗原环的人源单克隆抗体，在Ⅰ期研究中实现了血清HBsAg的快速下降。在一项多中心、开放性、部分剂量递增的Ib/IIa期研究中显示[4]，针对 HBeAg阴性、正在接受稳定NA背景治疗且HBsAg水平在100-3000 IU/mL之间的CHB患者，所有接受HT-101+HT-102 联合治疗12周的参与者，64.3%（18/28例）患者实现了HBsAg消失，值得注意的是，高剂量组（HT-101 400 mg + HT-102 300 mg）中有20%（2/10例）的参与者在治疗第4周就实现了HBsAg消失。基线HBsAg<1000 IU/mL的参与者中，92.8%（13/14例）实现了HBsAg消失；基线HBsAg≥1000 IU/mL的参与者中，有35.7%（5/14例）实现了HBsAg消失。各治疗组随时间不同HBsAg水平的患者占比（图源：文献4）另外，治疗耐受性良好，大多数治疗相关不良事件为1-2级（如注射部位反应）。未观察到药物相关的严重不良事件、≥3级事件、丙氨酸氨基转移酶（ALT）骤升或其他安全信号。 Part.4 BRII-179序贯Elebsiran+PEG-IFN-α-2a BRII-179是一种含Pre-S1/Pre-S2/S三种抗原的治疗性疫苗，Elebsiran是一种靶向HBV的小干扰RNA药物。一项多中心、开放标签II期研究[5]，评估了BRII-179序贯Elebsiran联合聚乙二醇干扰素α-2a（PEG-IFN-α-2a）进行治疗的疗效和安全性。研究纳入标准为：HBeAg阴性、HBV DNA<20 IU/mL（接受NA治疗中）、HBsAg>10 IU/mL且≤3000 IU/mL、抗-HBs <10 mIU/mL的非肝硬化CHB患者。研究分为两个阶段： ①预激阶段：所有患者在第0、4、12周皮下注射BRII-179（50 μg），在第12周评估CHB患者对BRII-179的抗体应答。 ②联合治疗阶段：自第24周起，所有患者继续接受皮下注射Elebsiran（200 mg，每4周一次）联合PEG-IFN-α-2a（180 μg，每周一次）治疗，持续24周，直至第48周。截至2023年7月，有45名患者完成治疗，并接受24周的随访（第72周），有12名（26.7%）实现了持续HBsAg清除（HBsAg<0.05 IU/mL）。根据BRII-179应答状态进行分层分析显示：在治疗第12周被归类为 BRII-179“应答者”（n=20）的患者中，有50%（10名）在第72周实现了持续HBsAg清除，并HBV DNA持续检测不到。在治疗第12周被归类为 BRII-179“无应答者”（n=25）中，仅有8.0%（2名）实现了持续HBsAg清除，并HBV DNA持续检测不到。 *1例受试者在第24周时HBsAg水平低于0.05 IU/mL，但后续在第48周前出现反弹；另有2例受试者在第24-48周期间实现HBsAg清除各治疗组随时间在不同HBsAg水平的患者占比（图源：文献5）安全性方面，治疗耐受性良好，大多数不良事件与PEG-IFN-α-2a的已知副作用（如流感样症状、疲劳、中性粒细胞减少）一致，且严重程度为轻度至中度。未发现与BRII-179或Elebsiran相关的意外安全信号。【最后一天】免费领取——《消化科医师处方手册》 1. 点击下方公众号名片，关注“医会宝消化肝病视界” 2. 进入公众号，后台回复“处方”参与领取！ END 参考文献： [1]何婧雯,柏涛,韩阳.慢性乙肝功能性治愈新型药物研发与治疗策略优化的研究进展[J/OL].医药导报,1-26[2026-01-16]. [2]High Proportion of Participants Achieved Sustained Complete Response 24 Weeks After Discontinuation of AHB-137 Treatment in HBeAg-Negative Chronic Hepatitis B Patients Receiving Nucleos(t)ide Analog Therapy: Pooled Analysis of Two Phase 2 Studies Conducted in China. AASLD2025, Late-Breaking Abstract (5022). [3]Safety and Preliminary Efficacy of GST-HG131, A First-in-Class Oral HBsAg Inhibitor, in Patients with Chronic Hepatitis B: Phase 2 Clinical Trial Data. AASLD2025, Late-Breaking Abstract (5022). [4]Liang XE, et al. Combination therapy with HT-101 and HT-102 achieved rapid and progressive HBsAg loss in HBeAg-negative, nucleos(t)ide analogues-suppressed patients: 12-week interim results from an ongoing multicentre, open-label phase Ib/IIa study. AASLD2025, Late-Breaking Abstract (5013). [5]Chronic Hepatitis B Virus-Infected Participants Responding to Prior BRII-179 Treatment Achieve Higher Rates of Sustained Hepatitis B Surface Antigen Loss with Elebsiran Plus Pegylated Interferon Alfa: Follow-Up Data from the ENSURE Study. AASLD2025, Late-Breaking Abstract (5036). 声明：本文出自医会宝编辑部，旨在为医疗专业人士传递更多医学信息。本文并不能取代医生的专业诊疗意见，如有罹患，需前往专业医院检查诊断。致：读者朋友为了不让大家错过医会宝消化肝病视界晚上17:30推送的医学知识和前沿资讯下面教大家如何第一时间接收到我们的推文：点击文章开头上方“医会宝消化肝病视界”→点击右上角“…” →点选“设为星标 ★ ” 加上星标这样就不会找不到我们啦！

100 项与 Hepatitis B (rDNA) vaccine(GlaxoSmithKline Plc) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J07BC01	DB11627

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
乙型肝炎	欧盟	GlaxoSmithKline Biologicals SA	2005-02-02
乙型肝炎	冰岛	GlaxoSmithKline Biologicals SA	2005-02-02
乙型肝炎	列支敦士登	GlaxoSmithKline Biologicals SA	2005-02-02
乙型肝炎	挪威	GlaxoSmithKline Biologicals SA	2005-02-02

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05561673 (CTgov)	临床1期	乙型肝炎	122	GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide (HBs-alum Group)	築膚積襯願顧獵廠繭衊 = 壓範膚觸築衊壓壓願餘築鏇範築壓壓範醖獵簾 (衊鑰構範餘壓膚範醖壓, 廠顧製構襯構鬱遞淵遞 ~ 糧築繭醖鹹構餘選網遞) 更多	-	2026-01-15
				GSK's AS03 adjuvant system+HBsAg candidate vaccine (HBs-AS03 Group)	築膚積襯願顧獵廠繭衊 = 廠鬱鑰糧餘憲鏇獵餘蓋築鏇範築壓壓範醖獵簾 (衊鑰構範餘壓膚範醖壓, 繭獵襯鏇衊窪觸積網範 ~ 顧蓋淵繭鏇簾醖壓餘簾) 更多
NCT03410953 (not provided, CTgov)	临床4期	乙型肝炎	67	Fendrix suspension	艱繭齋蓋襯窪壓網壓築 = 鬱鏇選鹹顧夢鹽窪餘膚繭顧憲糧積鏇艱齋獵壓 (壓鑰願積構鬱選繭膚廠, 鹹顧壓願衊鬱製繭鏇窪 ~ 簾蓋醖膚顧獵獵製糧願) 更多	-	2021-07-08
NCT03410953 (not provided, Pubmed \| Vaccine)	临床4期	-	67	Fendrix®	構醖憲夢顧齋淵製鬱壓(醖鑰憲鏇獵顧夢範膚醖) = 繭糧夢淵獵淵鑰齋獵衊醖夢夢遞鏇餘鹹鏇繭憲 (衊艱艱壓獵餘鹹鏇壓範 ) 更多	积极	2021-01-15
UEGW2014	N/A	炎症性肠病	-	two vaccines against Hepatitis B virus (HBV) (Fendrix)	觸遞鬱糧夢網製鬱壓憲(壓顧艱繭廠鏇淵鹽窪範) = 13% suffered adverse events (only 41% related with the vaccine, and all of them mild) 構膚繭網網鏇繭繭憲鏇 (獵簾夢窪積構鹹鏇遞衊 )	-	2014-10-01
				two vaccines against Hepatitis B virus (HBV) (Engerix)