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首页> 外文期刊>Vaccine >Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: A dose and route conundrum
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Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: A dose and route conundrum

机译：表达HCV NS4的重组腺病毒载体在牛痘-HCV病毒感染的小鼠模型中诱导保护性免疫应答：剂量和途径难题

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Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens. In this study, we sought to evaluate cellular and humoral immune responses against HCV NS4 protein using recombinant adenovirus as a vaccine vector expressing NS4 antigen. We have also measured the effect of antigen doses and routes of immunization on the quality and extent of the immune responses, especially their role in viral load reduction, in a recombinant Vaccinia-HCV (Vac-HCV) infection mouse model. Our results show that an optimum dose of adenovirus vector (2 x 10(7) pfu/mouse) administered intramuscularly (i.m.) induces high T cell proliferation, granzyme B-expressing CD8(+) T cells, pro-inflammatory cytokines such as IFN-gamma, TNF-alpha, IL-2 and IL-6, and antibody responses that can significantly reduce the Vac-HCV viral load in the ovaries of female C57BL/6 mice. Our results demonstrate that recombinant adenovirus vector can induce both humoral and cellular protective immunity against HCV-NS4 antigen, and that immunity is intricately controlled by route and dose of immunizing vector
机译：丙型肝炎病毒（HCV）在大多数感染患者中导致慢性感染，大概是由于所产生的免疫反应失败或效率低下。抗体和细胞免疫反应都被认为在病毒清除中很重要。表达目的抗原的非复制性腺病毒载体被认为是许多病原体的有吸引力的疫苗载体。在这项研究中，我们试图使用重组腺病毒作为表达NS4抗原的疫苗载体，评估针对HCV NS4蛋白的细胞和体液免疫反应。在重组牛痘-HCV（Vac-HCV）感染小鼠模型中，我们还测量了抗原剂量和免疫途径对免疫反应质量和程度的影响，尤其是它们在减少病毒载量中的作用。我们的结果表明，肌内（im）施用最佳剂量的腺病毒载体（2 x 10（7）pfu /小鼠）诱导高T细胞增殖，表达粒酶B的CD8（+）T细胞，促炎性细胞因子（如IFN） -γ，TNF-α，IL-2和IL-6，以及可显着降低雌性C57BL / 6小鼠卵巢Vac-HCV病毒载量的抗体反应。我们的结果表明重组腺病毒载体可以诱导针对HCV-NS4抗原的体液和细胞保护性免疫，并且免疫力受免疫载体的途径和剂量的控制

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