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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation of NF-κB by the intracellular expression of NF-κB-inducing kinase acts as a powerful vaccine adjuvant
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Activation of NF-κB by the intracellular expression of NF-κB-inducing kinase acts as a powerful vaccine adjuvant

机译：NF-κB诱导激酶在细胞内表达对NF-κB的激活是一种强大的疫苗佐剂

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摘要

There is a pressing need for adjuvants that will enhance the effectiveness of genetic vaccines. This is particularly important in cancer and infectious disease such as HIV and malaria for which successful vaccines are desperately needed. Here, we describe an approach to enhance immunogenicity that involves the activation of NF-κB by the transgenic expression of an intracellular signaling molecule, NF-κB-inducing kinase (NIK). In vitro, NIK increases dendritic cell antigen presentation in allogeneic and antigen-specific T cell proliferation assays by potently activating NF-κB and consequently up-regulating the expression of cytokines (TNF-α, IL-6, IL-12, IL-15, and IL-18), chemokines [IL-8, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1α, monocyte chemoattractant protein-1, and monocyte chemoattrac-tant protein-3], MHC antigen-presenting molecules (class Ⅰ and Ⅱ), and costimulatory molecules (CD80 and CD86). In vivo, NIK enhances immune responses against a vector-encoded antigen and shifts them toward a T helper 1 immune response with increased IgG2a levels, T cell proliferation, IFN-γ production, and cytotoxic T lymphocyte responses more potently than complete Freund's adjuvant, a very efficacious T helper 1-inducing adjuvant. These findings define NIK, and possibly other inducers of NF-κB activation, as a potent adjuvant strategy that offers great potential for genetic vaccine development.
机译：迫切需要佐剂，以提高基因疫苗的有效性。这在急需成功疫苗的癌症和感染性疾病（如HIV和疟疾）中尤其重要。在这里，我们描述了一种增强免疫原性的方法，其中涉及通过细胞内信号传导分子NF-κB诱导激酶（NIK）的转基因表达来激活NF-κB。在体外，NIK通过有效激活NF-κB并因此上调细胞因子（TNF-α，IL-6，IL-12，IL-15）的表达，提高了同种异体和抗原特异性T细胞增殖试验中树突状细胞抗原的表达。和IL-18），趋化因子[IL-8，RANTES（受激活，正常T细胞表达和分泌的调节），巨噬细胞炎性蛋白1α，单核细胞趋化蛋白1和单核细胞趋化蛋白3]，MHC抗原呈递分子（Ⅰ和Ⅱ类）和共刺激分子（CD80和CD86）。在体内，NIK增强了针对载体编码抗原的免疫反应，并使它们朝着T辅助1免疫反应转变，与完整的弗氏佐剂相比，IgG2a水平提高，T细胞增殖，IFN-γ产生和细胞毒性T淋巴细胞反应更有效。非常有效的T辅助剂1诱导佐剂。这些发现将NIK以及可能的其他NF-κB激活诱导剂定义为有效的佐剂策略，为基因疫苗的开发提供了巨大的潜力。

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