针对乙型肝炎病毒的腺病毒载体疫苗的免疫原性：非人灵长

StephenW

Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates

    Xuefeng Zhang, Jing Wang, Jing Lu, Rongrong Li and Shuli ZhaoEmail author

Virology Journal201815:111

https://doi.org/10.1186/s12985-018-1026-3

©  The Author(s). 2018

    Received: 20 April 2018Accepted: 16 July 2018Published: 24 July 2018

Abstract
Background

A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment.
Methods

The virus was subcutaneously administered at 1.0 × 109 viral particles (VP)/animal (low-dose group), 1.0 × 1010 VP/animal (mid-dose group), and 1.0 × 1011 VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 1011 VP/animal) and saline only.
Results

Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group.
Conclusions

Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine.

StephenW

针对乙型肝炎病毒的腺病毒载体疫苗的免疫原性：非人灵长类动物的非临床安全性评估

    张雪峰，王静，李静，李荣荣，赵淑丽，电子邮件作者

Virology Journal201815：111

https://doi.org/10.1186/s12985-018-1026-3

©The Author（s）。 2018

    收稿日期：2018年4月20日接受日期：2018年7月16日出版日期：2018年7月24日

抽象
背景

随着非复制型腺病毒载体候选疫苗（Ad-HBV）的发展，对于乙型肝炎病毒（HBV）慢性感染的患者出现了一种新的有希望的治疗方法。该疫苗编码由截短的HBV核心蛋白，突变的聚合酶蛋白和两个包膜结构域组成的融合蛋白。在本研究中，我们评估了在非临床安全性评估期间给予食蟹猴的Ad-HBV的免疫原性。
方法

病毒以1.0×109病毒颗粒（VP）/动物（低剂量组），1.0×1010 VP /动物（中剂量组）和1.0×1011 VP /动物（高剂量组）皮下给药;对照组仅给予Ad5-null病毒（1.0×1011 VP /动物）和盐水。
结果

除注射部位皮肤下的炎性细胞浸润和体温和血清白蛋白的短暂升高外，任何治疗组均未发现Ad-HBV相关的毒性作用。此外，干扰素（IFN）-γ酶联免疫斑点测定显示Ad-HBV诱导T细胞靶向广泛的HBV特异性表位，跨越所有三种选定的HBV免疫原（核心，聚合酶和包膜结构域）以剂量依赖的方式。尽管在所有组中产生抗Ad抗体（盐水对照除外），但高剂量Ad-HBV组中的抗体滴度显着低于接受相同剂量的Ad-null空载体的组中的抗体滴度。此外，对于中剂量，高剂量和Ad-null对照组，肝脏中的IFN-γ和IL-2表达水平显着改善（p <0.05），但对于低剂量组则不然。
结论

总之，该安全性评估表明Ad-HBV候选疫苗是有效的特异性免疫治疗剂，支持其作为抗HBV感染疫苗的进一步临床开发。

StephenW

https://virologyj.biomedcentral. ... 6/s12985-018-1026-3