在用核酸聚合物REP 2139-Ca治疗期间观察到的乙型肝炎病毒表面

StephenW

J Viral Hepat. 2018 Nov 19. doi: 10.1111/jvh.13044. [Epub ahead of print]
Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139-Ca have no influence on treatment outcome and its detection by diagnostic assays.
Mijočević H1, Karimzadeh H1,2, Seebach J1, Usman Z3, Mamun AM4, Bazinet M5, Vaillant A5, Roggendorf M1.
Author information

1
    Institute of Virology, Technische Universität München, Munich, Germany.
2
    Department of Medicine II, University Hospital Munich-Grosshadern, Munich, Germany.
3
    Department of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität München, Munich, Germany.
4
    Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
5
    Replicor Inc, Montreal, Canada.

Abstract

The treatment of patients suffering from HBeAg positive chronic hepatitis B with REP 2139-Ca resulted in potent reductions in HBsAg and HBV DNA, seroconversion to anti-HBs and the establishment of functional control of infection. In this cohort of 12 patients, we investigated whether differences between HBsAg sequences might explain lack of response to REP 2139-Ca observed in 3 of 12 patients. We also assessed if the reduction or complete loss of HBsAg in serum observed during therapy were caused by mutations in the "a" determinant preventing the detection of HBsAg by standard diagnostic assays. The complete pre-S/S open reading frame (ORF) was sequenced and pre-S1, pre-S2 and S amino acid sequences were analysed. We found no major differences between pre-S1, pre-S2 and S sequences in responders and non-responders correlated with low reduction of HBsAg. In addition, we found no mutations in the "a" determinant that would significantly affect the reactivity of HBsAg in diagnostic assays. These results demonstrate that the amino acid sequence of complete pre-S/S ORF has no direct influence on response to REP 2139-Ca therapy. This article is protected by copyright. All rights reserved.
KEYWORDS:

HBsAg; Mutation; hepatitis B virus; nucleic acid polymer; therapy

PMID:
    30450662
DOI:
    10.1111/jvh.13044

StephenW

J病毒肝病。 2018年11月19日doi：10.1111 / jvh.13044。 [提前打印]
在用核酸聚合物REP 2139-Ca治疗期间观察到的乙型肝炎病毒表面抗原的变体对治疗结果及其通过诊断测定的检测没有影响。
MijočevićH1，Karimzadeh H1,2，Seebach J1，Usman Z3，Mamun AM4，Bazinet M5，Vaillant A5，Roggendorf M1。
作者信息

1
    德国慕尼黑工业大学病毒学研究所。
2
    慕尼黑大学医院II医学系 - 德国慕尼黑Grosshadern。
3
    生物信息学系，Wissenschaftszentrum Weihenstephan，慕尼黑工业大学，慕尼黑，德国。
4
    Bangabandhu Sheikh Mujib医科大学，孟加拉国达卡。
五
    Replicor Inc，加拿大蒙特利尔。

抽象

用REP 2139-Ca治疗患有HBeAg阳性慢性乙型肝炎的患者导致HBsAg和HBV DNA的有效减少，抗HBs的血清转化和感染的功能控制的建立。在这12名患者的队列中，我们研究了HBsAg序列之间的差异是否可以解释12名患者中有3名患者对REP 2139-Ca缺乏反应。我们还评估了治疗期间观察到的血清中HBsAg的减少或完全丧失是否是由于“a”决定因素的突变导致的，这种突变阻碍了标准诊断分析检测HBsAg。对完整的前S / S开放阅读框（ORF）进行测序，并分析前S1，前S2和S氨基酸序列。我们发现在应答者和无应答者中前S1，前S2和S序列之间没有显着差异与HBsAg的低减少相关。此外，我们发现“a”决定簇中没有突变会显着影响HBsAg在诊断分析中的反应性。这些结果表明，完整的前S / S ORF的氨基酸序列对REP 2139-Ca疗法的反应没有直接影响。本文受版权保护。版权所有。
关键词：

乙肝表面抗原;突变;乙型肝炎病毒;核酸聚合物;治疗

结论：
    30450662
DOI：
    10.1111 / jvh.13044

齐欢畅

有全文吗？

SK蜗牛

这个不是很懂什么意思哦

StephenW

回复 齐欢畅 的帖子

有，但不公开或免费.

StephenW

回复 StephenW 的帖子

这项研究调查了为什么3/12患者对REP2139没有反应.
这些结果表明，前S / S ORF的氨基酸序列对REP 2139-Ca疗法的反应没有直接影响.

Replicor不知道REP2139如何实际阻断HBsAg亚病毒颗粒的组装和释放.

StephenW

Replicor announces publication of new study validating HBsAg responses driven by REP 2139

MONTREAL, November 21st, 2018 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, announces the publication of new data validating the clearance of HBsAg in response to NAP therapy in the Journal of Viral Hepatitis (https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvh.13044).

The  article is entitled “Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139‐Ca have no influence on treatment outcome and its detection by diagnostic assays.” This study adds to data previously published from Replicor’s ongoing collaboration with Dr. Michael Roggendorf at the Technical University of Munich (TUM), Germany, confirming that the HBsAg reductions and loss of HBsAg which uniquely occur in a high proportion of patients receiving REP 2139 are real.

Dr. Andrew Vaillant, CSO at Replicor commented, “From the initiation of our first clinical study, NAP-based combination therapy was the first, and, is still the only therapeutic approach that consistently  demonstrates high rates of rapid serum HBsAg reduction and loss and restoration of control of HBV and HDV infection in the absence of therapy.  Understandably, these results led to some skepticism concerning the validity of the HBsAg losses occurring with REP 2139.  Early on in the clinical development of NAPs, we turned to Dr. Roggendorf and the virology group at TUM to demonstrate that these HBsAg losses are real and this publication is the second from this ongoing collaboration to show that REP 2139-mediated HBsAg loss is real.”

Previously published data in The Lancet Gastroenterology & Hepatology (https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30288-1/fulltext) demonstrated that REP 2139 does not interfere with a broad suite of protein and nucleic acid-based assays for HBV and HDV.  In the current study, HBsAg strains which cannot be detected by the industry standard HBsAg test platforms used in Replicor’s clinical studies were not observed at any time during REP 2139 exposure.  These data confirm the validity of HBsAg responses observed in all clinical studies with REP 2139-Ca or REP 2139-Mg.

Dr. Vaillant added, “This study also showed that HBsAg sequences present in different participants at baseline had no influence on their HBsAg response to REP 2139, consistent with our data showing that NAPs effect the assembly and secretion of subviral particles by interfering with a host protein involved in their formation.”

About Replicor

Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.

StephenW

Replicor宣布发布新的研究，验证REP 2139驱动的HBsAg反应

蒙特利尔，2018年11月21日 - Replicor Inc.是一家私人控股的生物制药公司，旨在治疗慢性乙型肝炎病毒（HBV）和慢性HBV和肝炎病毒（HDV）合并感染患者，宣布发布新数据验证病毒性肝炎杂志中针对NAP治疗的HBsAg清除率（https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvh.13044）。

该文章的标题是“在用核酸聚合物REP 2139-Ca治疗期间观察到的乙型肝炎病毒表面抗原变异对治疗结果和诊断检测的检测没有影响。”这项研究增加了以前从Replicor与Dr博士合作发表的数据。德国慕尼黑技术大学（TUM）的Michael Roggendorf证实HBsAg的减少和HBsAg的丢失在接受REP 2139的大部分患者中是独一无二的。

Replicor的CSO Andrew Vaillant博士评论说：“从我们的第一次临床研究开始，基于NAP的联合治疗是第一次，并且仍然是唯一一种能够持续证明血清HBsAg快速降低和丢失率的治疗方法。在没有治疗的情况下恢复对HBV和HDV感染的控制。可以理解的是，这些结果导致对REP 2139中HBsAg损失的有效性产生了一些怀疑。在NAP的临床开发早期，我们转向Roggendorf博士和TUM的病毒学组，以证明这些HBsAg损失是真实的，该出版物是此次合作中的第二份，表明REP 2139介导的HBsAg损失是真实的。“

以前在“柳叶刀胃肠病学和肝病学”（https://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30288-1/fulltext）上发表的数据表明REP 2139不会干扰广泛的基于蛋白质和核酸的HBV和HDV检测。在目前的研究中，在REP 2139暴露期间的任何时间都没有观察到Replicor临床研究中使用的行业标准HBsAg测试平台无法检测到的HBsAg菌株。这些数据证实了在REP 2139-Ca或REP 2139-Mg的所有临床研究中观察到的HBsAg反应的有效性。

Vaillant博士补充说：“这项研究还表明，基线时不同参与者中存在的HBsAg序列对他们对REP 2139的HBsAg反应没有影响，这与我们的数据一致，表明NAP通过干扰宿主影响亚病毒颗粒的组装和分泌。蛋白质参与其形成。“

关于Replicor

Replicor是一家私人持有的生物制药公司，拥有最先进的动物和人类临床数据，可用于治疗HBV和HDV。该公司致力于加速为HBV和HBV / HDV合并感染患者开发有效的治疗方案。有关Replicor的更多信息，请访问我们的网站www.replicor.com。

newchinabok

rep是黔驴技穷

StephenW

井底之蛙