Oral immunization with attenuated Salmonella carrying a co-expression plasmid encoding the core and E2 proteins of hepatitis C virus capable of inducing cellular immune responses and neutralizing antibodies in mice
Oral immunization with attenuated Salmonella carrying a co-expression plasmid encoding the core and E2 proteins of hepatitis C virus capable of inducing cellular immune responses and neutralizing antibodies in mice
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使用携带共表达质粒的减毒沙门氏菌进行口服免疫，该质粒编码丙型肝炎病毒的核心蛋白和E2蛋白，能够在小鼠中诱导细胞免疫反应并中和抗体。
DOI：
10.1016/j.vaccine.2011.02.083
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发表时间：
2011-05-09
期刊：
影响因子：
5.5
通讯作者：
Qi, Zhongtian
中科院分区：
文献类型：
--
作者：
Cao, Jie;Chen, Zhihui;Qi, Zhongtian
丙型肝炎病毒（HCV）核心蛋白长期以来一直被认为是包含在保护性疫苗中的有吸引力的候选者。然而，由于其免疫抑制特性，这种蛋白质可能会阻碍全身免疫反应的发展。我们之前报道过，携带 HCV 核心蛋白的减毒沙门氏菌可以有效诱导对 HCV 核心蛋白的免疫反应，但 HCV 核心 DNA 疫苗则不能。为了优化疫苗制剂中核心蛋白和包膜蛋白 2 (E2) 的组合以诱导细胞免疫反应和中和抗体，我们构建了包含两个表达盒的质粒。包括一个表达盒以通过可诱导的体内激活沙门氏菌启动子调节HCV核心蛋白的表达，包括另一个表达盒以通过巨细胞病毒增强子/启动子调节HCV E2蛋白的表达。用携带该质粒的减毒沙门氏菌菌株 SL7207 口服免疫 BALB/c 小鼠，可有效诱导 HCV 核心和 E2 特异性细胞免疫反应和抗体。从免疫小鼠中纯化的 IgG 可以中和自体 Con 1 分离株和异源 H77 分离株的 HCV 假颗粒 (HCVpp) 的感染性，细胞培养产生 Con1-JFH1 嵌合体的 HCV (HCVcc)。这些结果表明，该疫苗策略可以有效地将核心蛋白和E2蛋白递送至免疫系统，并为开发针对HCV感染的预防性和治疗性疫苗提供了一种有前景的方法。 Crown 版权所有 (C) 2011 由 Elsevier Ltd 出版。保留所有权利。
Hepatitis C virus (HCV) core protein has long been considered an attractive candidate for inclusion in a protective vaccine. However, this protein may hamper the development of systemic immune responses because of its immune suppressive properties. We previously reported that immune responses to HCV core protein could be efficiently induced by attenuated Salmonella carrying the HCV core protein, but not the HCV core DNA vaccine. To optimize the combination of the core protein and envelope protein 2 (E2) into a vaccine formulation to induce cellular immune responses and neutralizing antibodies, we constructed a plasmid containing two expression cassettes. One expression cassette was included to regulate the expression of HCV core protein by an inducible in vivo-activated Salmonella promoter, the other was included to regulate the expression of HCV E2 protein by the cytomegalovirus enhancer/promoter. Oral immunization of BALB/c mice with the attenuated Salmonella strain SL7207 carrying this plasmid efficiently induced HCV core and E2-specific cellular immune responses and antibodies. IgG purified from immunized mice could neutralize the infectivity of HCV pseudoparticles (HCVpp) of both the autologous Con 1 isolate and the heterologous H77 isolate, and cell culture produced HCV (HCVcc) of Con1-JFH1 chimera. These results indicated that this vaccine strategy can effectively deliver core and E2 protein to the immune system and provide a promising approach for the development of prophylactic and therapeutic vaccines against HCV infection. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.