表达多种抗原的病毒样囊泡用于慢性乙型肝炎的免疫治疗。

StephenW

iScience. 2019 Oct 24;21:391-402. doi: 10.1016/j.isci.2019.10.040. [Epub ahead of print]
Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B.
Yarovinsky TO1, Mason SW2, Menon M2, Krady MM2, Haslip M2, Madina BR2, Ma X2, Moshkani S3, Chiale C3, Pal AC4, Almassian B2, Rose JK4, Robek MD3, Nakaar V5.
Author information

1
    CaroGen Corporation, Farmington, CT 06032, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: [email protected].
2
    CaroGen Corporation, Farmington, CT 06032, USA.
3
    Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
4
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
5
    CaroGen Corporation, Farmington, CT 06032, USA. Electronic address: [email protected].

Abstract

Infections with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B are inadequate and leave an unmet need for immunotherapeutic approaches. We designed virus-like vesicles (VLV) as self-amplifying RNA replicons expressing three HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV) to break immune exhaustion despite persistent HBV replication. The HBV-VLV induces HBV-specific T cells in naive mice and renders them resistant to acute challenge with HBV. Using a chronic model of HBV infection, we demonstrate efficacy of HBV-VLV priming in combination with DNA booster immunization, as 40% of treated mice showed a decline of serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of HBV-VLV for immunotherapy of chronic hepatitis B.

Copyright © 2019. Published by Elsevier Inc.
KEYWORDS:

Immunology; Medical Microbiology; Virology

PMID:
    31704650
DOI:
    10.1016/j.isci.2019.10.040

StephenW

科学。 2019十月24; 21：391-402。 doi：10.1016 / j.isci.2019.10.040。 [Epub提前发布]
表达多种抗原的病毒样囊泡用于慢性乙型肝炎的免疫治疗。
Yarovinsky TO1，Mason SW2，Menon M2，Krady MM2，Haslip M2，Madina BR2，Ma X2，Moshkani S3，Chiale C3，Pal AC4，Almassian B2，Rose JK4，Robek MD3，Nakaar V5。
作者信息

1个
    美国，CT 06032，法明顿，CaroGen公司；耶鲁大学医学院病理学系，美国康涅狄格州纽黑文06510。电子地址：[email protected]。
2
    CaroGen Corporation，法明顿，CT 06032，美国。
3
    美国纽约州奥尔巴尼市奥尔巴尼医学院免疫学和微生物病系。
4
    耶鲁大学医学院病理学系，美国康涅狄格州纽黑文06510。
5
    CaroGen Corporation，法明顿，CT 06032，美国。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）感染可引发慢性肝炎和肝损伤，全世界每年造成600,000多人死亡。当前对慢性乙型肝炎的治疗是不足的，并且对免疫治疗方法的需求未得到满足。我们将病毒样囊泡（VLV）设计为可自我扩增的RNA复制子，可从单个载体（HBV-VLV）表达三种HBV抗原（聚合酶，核心和中间表面），从而在持续HBV复制的情况下破坏免疫力。 HBV-VLV可以在幼稚小鼠中诱导HBV特异性T细胞，并使其抵抗HBV的急性攻击。使用HBV感染的慢性模型，我们证明了HBV-VLV引发与DNA加强免疫相结合的功效，因为40％的受治疗小鼠显示血清HBV表面抗原下降到检测限以下，并且肝HBV RNA显着降低，并伴有HBsAg特异性CD8 T细胞的诱导。这些结果值得进一步评估HBV-VLV用于慢性乙型肝炎的免疫治疗。

版权所有©2019.由Elsevier Inc.发行
关键字：

免疫学医学微生物学病毒学

PMID：
    31704650
DOI：
    10.1016 / j.isci.2019.10.040

StephenW

https://www.cell.com/iscience/pdf/S2589-0042(19)30420-1.pdf