Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates.
Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates.
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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
DOI：
10.1186/s12985-018-1026-3
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发表时间：
2018-07-24
期刊：
影响因子：
4.8
通讯作者：
Zhao S
中科院分区：
文献类型：
--
作者：
Zhang X;Wang J;Lu J;Li R;Zhao S
随着非复制型腺病毒载体疫苗(Ad-HBV)的发展，一种新的治疗慢性乙肝病毒感染的方法出现了。该疫苗编码一种融合蛋白，由截短的乙肝核心蛋白、突变的聚合酶蛋白和两个包膜结构域组成。方法用1.0 × 10 9病毒颗粒(VP)/动物(低剂量组)、1.0 × 10 10VP/动物(中剂量组)、1.0 × 10 11VP/动物(高剂量组)皮下注射病毒；结果除注射部位皮下炎细胞浸润和一过性体温升高、血清白蛋白升高外，其余各治疗组均未见与AdHBV1 0 × 1011VP/只相关的毒性反应。此外，干扰素-γ酶联免疫斑点分析显示，Ad-HBV腺病毒以剂量依赖的方式诱导T细胞靶向跨越所有三种选定的乙肝免疫原(核心区、聚合酶和包膜区)的广泛的乙肝病毒特异性表位。除生理盐水对照组外，其余各组均产生抗Ad抗体，但高剂量Ad-HBV组的抗体滴度明显低于相同剂量的空载体Ad组。此外，中剂量组、高剂量组和空白组肝脏中干扰素-γ和IL-2的表达水平显著提高(p<；HBV0.0 5)，而低剂量组未见明显改善。结论本研究的安全性评价结果表明，Ad- 候选疫苗是一种有效的特异性免疫治疗剂，支持其作为临床抗乙肝疫苗的进一步发展。
BackgroundA 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.MethodsThe virus was subcutaneously administered at 1.0 × 109viral particles (VP)/animal (low-dose group), 1.0 × 1010VP/animal (mid-dose group), and 1.0 × 1011VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 1011VP/animal) and saline only.ResultsExcept 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.ConclusionsTaken 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.
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影响因子：
2.5
作者：
Mendy ME;Welzel T;Lesi OA;Hainaut P;Hall AJ;Kuniholm MH;McConkey S;Goedert JJ;Kaye S;Rowland-Jones S;Whittle H;Kirk GD
通讯作者：
Kirk GD
影响因子：
--
作者：
Fu, Haiyan;Meadows, Aaron S.;McCarty, Douglas M.
通讯作者：
McCarty, Douglas M.
影响因子：
7.3
作者：
Maini MK;Peppa D
通讯作者：
Peppa D
影响因子：
4.4
作者：
Zheng, Meijuan;Sun, Rui;Tian, Zhigang
通讯作者：
Tian, Zhigang
影响因子：
4
作者：
Wilson RC;Gilbert LA
通讯作者：
Gilbert LA