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首页> 外文期刊>Vaccine >Targeting of nucleoprotein to chemokine receptors by DNA vaccination results in increased CD8(+)-mediated cross protection against influenza
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Targeting of nucleoprotein to chemokine receptors by DNA vaccination results in increased CD8(+)-mediated cross protection against influenza

机译：通过DNA疫苗将核蛋白靶向趋化因子受体可导致CD8（+）介导的针对流感的交叉保护增加

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Vaccination is at present the most efficient way of preventing influenza infections. Currently used inactivated influenza vaccines can induce virus-neutralizing antibodies that are protective against a particular influenza strain, but hamper the induction of cross-protective T-cell responses to later infections. Thus, influenza vaccines need to be updated annually in order to confer protection against circulating influenza strains. This study aims at developing an efficient vaccine that can induce broader protection against influenza. For this purpose, we have used the highly conserved nucleoprotein (NP) from an influenza A virus subtype H7N7 strain, and inserted it into a vaccine format that targets an antigen directly to relevant antigen presenting cells (APCs). The vaccine format consists of bivalent antigenic and targeting units, linked via an Ig-based dimerization unit. In this study, NP was linked to MIP-1 alpha, a chemokine that targets the linked antigen to chemokine receptors 1,3 and 5 expressed on various APCs. The vaccine protein was indirectly delivered by DNA. Mice were vaccinated intradermally with plasmids, in combination with electroporation to enhance cellular uptake of DNA. We found that a single DNA vaccination was sufficient for induction of both antibody and T cell responses in BALB/c mice. Targeting of nucleoprotein to chemokine receptors enhanced T cell responses but not antibody responses. Moreover, a single dose of MIP1 alpha-NP conferred protection in BALB/c mice against a lethal challenge with an H1N1 influenza virus. The observed cross-protection was mediated by CD8(+) T cells. (C) 2015 The Authors. Published by Elsevier Ltd.
机译：疫苗接种是目前预防流感感染的最有效方法。当前使用的灭活流感疫苗可以诱导对特定流感病毒株具有保护作用的病毒中和抗体，但会阻碍对以后感染的交叉保护性T细胞反应的诱导。因此，流感疫苗需要每年更新以赋予针对流行的流感病毒株的保护。这项研究旨在开发一种有效的疫苗，可以诱导更广泛的针对流感的保护。为此，我们使用了来自甲型流感病毒H7N7亚型的高度保守的核蛋白（NP），并将其插入了将抗原直接靶向相关抗原呈递细胞（APC）的疫苗形式。疫苗形式由通过基于Ig的二聚体单元连接的二价抗原和靶向单元组成。在这项研究中，NP与MIP-1 alpha相连，MIP-1 alpha是一种趋化因子，其靶向的抗原指向在各种APC上表达的趋化因子受体1,3和5。疫苗蛋白是通过DNA间接递送的。将小鼠皮内接种质粒，并结合电穿孔以增强细胞对DNA的吸收。我们发现单个DNA疫苗接种足以诱导BALB / c小鼠中的抗体和T细胞应答。核蛋白靶向趋化因子受体增强了T细胞反应，但没有抗体反应。此外，单剂量的MIP1α-NP可以使BALB / c小鼠免受H1N1流感病毒的致命攻击。观察到的交叉保护是由CD8（+）T细胞介导的。 （C）2015作者。由Elsevier Ltd.发布

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