Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection
Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection
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DOI：
10.1073/pnas.1131929100
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发表时间：
2003-05-27
影响因子：
11.1
通讯作者：
Liang, TJ
中科院分区：
文献类型：
--
作者：
Murata, K;Lechmann, M;Liang, TJ
我们最近已经证明，用昆虫细胞中产生的丙型肝炎病毒样颗粒（HCV-LPs）免疫BALB/c小鼠可以引起体液和细胞免疫应答。在这里，我们评估的免疫原性HCV-LPs在HLA2.1转基因（AAD）小鼠相比，DNA免疫。HCV-LP免疫诱导的体液免疫应答明显强于DNA免疫。HCV-LP免疫小鼠也比DNA免疫小鼠产生更强的HCV特异性细胞免疫应答，如通过使用定量酶联免疫斑点（ELISpot）测定和细胞内细胞因子染色所确定的。在BALB/c小鼠中，当用表达HCV结构蛋白（vvHCV.S）的重组牛痘攻击时，用HCV-LP免疫导致牛痘滴度降低>5 log（10），而DNA免疫则降低1 log（10）。在HLA2.1转基因小鼠中，HCV-LP免疫导致1- 2log（10）减少，而DNA免疫没有观察到减少。从HCV-LP免疫的小鼠向幼稚小鼠的淋巴细胞连续转移提供了针对vvHCV.S攻击的保护，并且这种转移的免疫可以通过CD 4或CD 8耗竭而消除。我们的研究结果表明，HCV-LP可以诱导体液和细胞免疫反应，是保护在替代HCV的挑战模型和强大的细胞免疫提供的CD 4和CD 8效应淋巴细胞可能是重要的HCV感染的保护。
We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immunization elicited a significantly stronger humoral immune response than DNA immunization. HCV-LP-immunized mice also developed stronger HCV-specific cellular immune responses than DNA-immunized mice as determined by using quantitative enzyme-linked immunospot (ELISpot) assay and intracellular cytokine staining. In BALB/c mice, immunization with HCV-LPs resulted in a >5 log(10) reduction in vaccinia titer when challenged with a recombinant vaccinia expressing the HCV structural proteins (vvHCV.S), as compared to 1 log(10) decrease in DNA immunization. In HLA2.1 transgenic mice, a 1-2 log(10) reduction resulted from HCV-LP immunization, whereas no reduction was seen from DNA immunization. Adoptive transfer of lymphocytes from HCV-LP-immunized mice to naive mice provided protection against vvHCV.S challenge, and this transferred immunity can be abrogated by either CD4 or CD8 depletion. Our results suggest that HCV-LPs can induce humoral and cellular immune responses that are protective in a surrogate HCV challenge model and that a strong cellular immunity provided by both CD4 and CD8 effector lymphocytes may be important for protection from HCV infection.