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优化新型蛋白基和重组天坛痘苗（Tiantan）乙型肝炎病毒（HBV）疫苗在小鼠中的初免-加强免疫。

Optimisation of prime-boost immunization in mice using novel protein-based and recombinant vaccinia (Tiantan)-based HBV vaccine.

机构信息

Biotech Center for Viral Diseases Emergency, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.

出版信息

PLoS One. 2012;7(9):e43730. doi: 10.1371/journal.pone.0043730. Epub 2012 Sep 6.

DOI:10.1371/journal.pone.0043730
PMID:22970140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3435326/
Abstract

BACKGROUND

A therapeutic vaccine for chronic hepatitis B virus (HBV) infection that enhances virus-specific cellular immune responses is urgently needed. The "prime-boost" regimen is a widely used vaccine strategy against many persistence infections. However, few reports have addressed this strategy applying for HBV therapeutic vaccine development.

METHODOLOGY/PRINCIPAL FINDINGS: To develop an effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus (Tiantan) containing the S+PreS1 fusion antigen (RVJSS1) combined with the HBV particle-like subunit vaccine HBVSS1 to explore the most effective prime-boost regimen against HBV. The immune responses to different prime-boost regimens were assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine staining analysis. Among the combinations tested, an HBV protein particle vaccine priming and recombinant vaccinia virus boosting strategy accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres as well as the strongest multi-antigen (PreS1, and S)-specific cellular immune response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF-α and IFN-γ).

CONCLUSIONS

The HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future HBV therapeutic vaccines.

摘要

背景

目前迫切需要一种能够增强乙型肝炎病毒（HBV）特异性细胞免疫应答的慢性 HBV 感染治疗性疫苗。“初始-加强”方案是一种广泛用于针对许多持续性感染的疫苗策略。然而，针对 HBV 治疗性疫苗开发，很少有报道涉及这种策略。

方法/主要发现：为了开发有效的 HBV 治疗性疫苗，我们构建了一种含有 S+PreS1 融合抗原（RVJSS1）的重组痘苗病毒（天坛），并与 HBV 颗粒样亚单位疫苗 HBVSS1 联合，以探索针对 HBV 的最有效的初始-加强方案。通过 ELISA、ELISpot 测定和细胞内细胞因子染色分析，在 C57BL/C 小鼠中评估了不同初始-加强方案的免疫应答。在测试的组合中，HBV 蛋白颗粒疫苗初始和重组痘苗病毒加强策略加速了特异性血清转换，并产生了高抗体（抗-PreS1、抗-S 抗体）滴度以及最强的多抗原（PreS1 和 S）特异性细胞免疫应答。HBSS1 蛋白疫苗初始/RVJSS1 载体加强免疫也产生了更高水平的 CD4+和 CD8+T 细胞应答，分泌 Th1 样细胞因子（TNF-α和 IFN-γ）。

结论

HBSS1 蛋白疫苗初始加 RVJSS1 载体加强免疫可诱导特异性抗体以及分泌 Th1 样细胞因子的 CD4 和 CD8 细胞，这些免疫应答可能是未来 HBV 治疗性疫苗的重要参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/414035b4033a/pone.0043730.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/cf7104e32188/pone.0043730.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/623913841ffd/pone.0043730.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/ce4905c34f9d/pone.0043730.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/c6df14b84065/pone.0043730.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/1ca5ab178356/pone.0043730.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/414035b4033a/pone.0043730.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/cf7104e32188/pone.0043730.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/623913841ffd/pone.0043730.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/ce4905c34f9d/pone.0043730.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/c6df14b84065/pone.0043730.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/1ca5ab178356/pone.0043730.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4708/3435326/414035b4033a/pone.0043730.g006.jpg

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