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首页> 美国卫生研究院文献>PLoS Clinical Trials >Suppressive Effects on the Immune Response and Protective Immunity to a JEV DNA Vaccine by Co-administration of a GM-CSF-Expressing Plasmid in Mice
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Suppressive Effects on the Immune Response and Protective Immunity to a JEV DNA Vaccine by Co-administration of a GM-CSF-Expressing Plasmid in Mice

机译：通过共同施用小鼠表达GM-CSF的质粒对JEV DNA疫苗的免疫应答和保护性免疫的抑制作用

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As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony–stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF.
机译：作为DNA疫苗的潜在细胞因子佐剂，粒细胞-巨噬细胞集落刺激因子（GM-CSF）由于其在抗原呈递细胞的募集，树突状细胞的分化和成熟中的重要作用而受到了广泛的关注。但是，在我们最近对日本脑炎病毒（JEV）DNA疫苗的研究中，共接种GM-CSF质粒可显着抑制特异性IgG反应，并导致对JEV攻击的保护作用降低。众所周知，GM-CSF已在临床上用于治疗嗜中性白血球减少症，以重新形成髓样细胞，并在疫苗研究中用作佐剂。它已显示出对免疫反应的多种作用。因此，在这项研究中，我们通过共同施用表达GM-CSF的质粒表征了对JEV DNA疫苗免疫应答的抑制作用，并阐明了抑制小鼠的潜在机制。我们的结果表明，与GM-CSF共同免疫可大大抑制疫苗诱导的抗体反应。抑制作用是剂量和时间依赖性的，并且可能与抗原的免疫原性有关。该抑制与未成熟树突状细胞的诱导和调节性T细胞的扩增有关，而与髓样来源的抑制性细胞无关。总的来说，我们的发现不仅为GM-CSF在临床中的应用和用作疫苗佐剂提供了有价值的信息，而且为深入了解GM-CSF的复杂作用提供了进一步的见识。

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