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Hepatits C virus (HCV) core protein enhances the immuningenicity of a co-delivered DNA vaccine encoding HCV structural antigens in mice

机译:丙型肝炎病毒(HCV)核心蛋白可增强共同提供的编码HCV结构抗原的DNA疫苗在小鼠中的免疫原性

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In the present study, recombinant HCV (hepatitis C virus) core proteins enhanced the immune response elicited by a co-delivered DNA vaccine encoding HCV core and envelope proteins. A mixture of the plasmid pIDKE2 and Co. 173, a protein comprising the first 173 amino acids of HCV core, in particular induces a strong humoral response, including antibodies that recognized peptides representing hypervariable region I from different viral isolates. Moreover, positive lymphoproliferative responses against the HCV structural proteins, encoded by the plasmid, were detected after two doses with this mixture. When the HCV core protein used in the mixture with pIDKE2 was Co.120, a protein comprising the first 120 amino acids of the viral antigen, a strong humoral response and a positive lymphoproliferative response were also detected. The effectiveness of this formulation was tested in vivo by measuring the protection against infection with a recombinant vaccinia virus expressing HCV core protein. A 2 log reduction in vaccinia-virus titre was observed in mice immunized with the mixture of pIDKE2 and Co.120. Humoral and cellular immune responses elicited for the mixture of pIDKE2 with either Co. 173 or Co. 120 was stronger and more diverse than those generated by individual components. In conclusion, our results indicate that formulations comprising both DNA constructs and protein subunit vaccine candidates are able to elicit strong humoral and cellular immunity against several antigens. Particularly, HCV core protein might be used as a feasible vehicle/adjuvant for DNA vaccines.
机译:在本研究中,重组HCV(丙型肝炎病毒)核心蛋白增强了由共同交付的编码HCV核心和包膜蛋白的DNA疫苗引起的免疫应答。质粒pIDKE2和Co.173(一种包含HCV核心的前173个氨基酸的蛋白质)的混合物特别诱导了强烈的体液应答,包括识别代表来自不同病毒分离株的高变区I的肽的抗体。而且,用该混合物两次给药后,检测到了对由质粒编码的HCV结构蛋白的阳性淋巴增生反应。当与pIDKE2的混合物中使用的HCV核心蛋白是Co.120时,还检测到了包含病毒抗原的前120个氨基酸的蛋白,强烈的体液反应和阳性的淋巴增生反应。通过测量针对表达HCV核心蛋白的重组痘苗病毒的感染防护,在体内测试了该制剂的有效性。在用pIDKE2和Co.120混合物免疫的小鼠中,牛痘病毒滴度降低了2 log。 pIDKE2与Co.173或Co.120的混合物引起的体液和细胞免疫应答比单个组分产生的应答更强和更多样化。总之,我们的结果表明,同时包含DNA构建体和蛋白质亚基疫苗候选物的制剂能够引发针对几种抗原的强体液和细胞免疫。特别地,HCV核心蛋白可以用作DNA疫苗的可行载体/佐剂。

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