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首页> 外文期刊>The journal of immunology >Essential Role for TLR9 in Prime but Not Prime-Boost Plasmid DNA Vaccination To Activate Dendritic Cells and Protect from Lethal Viral Infection
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Essential Role for TLR9 in Prime but Not Prime-Boost Plasmid DNA Vaccination To Activate Dendritic Cells and Protect from Lethal Viral Infection

机译：TLR9在初免而非初免-加强质粒DNA疫苗接种中的关键作用，以激活树突状细胞并保护其免受致命的病毒感染。

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One of the requirements for efficient vaccination against infection is to achieve the best combination of an adequate adjuvant with the antigenic information to deliver. Although plasmid DNA is a promising tool bearing the unique potential to activate humoral and cellular immunity, an actual challenge is to increase plasmid immunogenicity in human vaccination protocols in which efficacy has proven rather limited. Previous work showed that the bacterial DNA backbone of the plasmid has potent adjuvant properties because it contains CpG motifs that are particular activating nucleotidic sequences. Among TLRs, which are key sensors of microbial products, TLR9 can detect CpG motifs and confer activation of APCs, such as dendritic cells. However, whether the immunogenic properties of plasmid DNA involve TLR9 signaling has not been clearly established. In the current study, we demonstrate that TLR9 determines the effectiveness of vaccination against lethal lymphocytic choriomeningitis virus infection using plasmid DNA in a prime, but not prime-boost, vaccination regimen. Furthermore, we provide evidence that the presence of TLR9 in dendritic cells is necessary for effective and functional priming of virus-specific CD8+ T cells upon plasmid exposure in vitro or single-dose vaccination in vivo. Therefore, at single or low vaccine doses that are often used in human-vaccination protocols, CpG/TLR9 interactions participate in the immunogenicity of plasmid DNA. These results suggest that the TLR9 signaling pathway is involved in the efficacy of plasmid vaccination; therefore, it should remain a focus in the development or amelioration of vaccines to treat infections in humans.
机译：有效的疫苗接种抗感染的要求之一是实现适当佐剂与抗原信息的最佳结合。尽管质粒DNA是一种有前途的工具，具有激活体液和细胞免疫的独特潜力，但实际的挑战是提高人类疫苗接种方案中的质粒免疫原性，而事实证明这种疫苗的功效相当有限。先前的工作表明，该质粒的细菌DNA主链具有有效的佐剂特性，因为它含有CpG模体，这些模体是特定的激活核苷酸序列。在作为微生物产品关键传感器的TLR中，TLR9可以检测CpG图案并赋予APC（如树突状细胞）激活作用。但是，尚不清楚质粒DNA的免疫原性是否涉及TLR9信号转导。在当前的研究中，我们证明TLR9可以在主要但不是初次加强接种方案中使用质粒DNA来确定针对致死性淋巴细胞性脉络膜脑膜炎病毒感染的接种有效性。此外，我们提供证据表明，在体外质粒暴露或体内单剂量疫苗接种后，树突状细胞中TLR9的存在对于有效和功能性引发病毒特异性CD8 + T细胞是必要的。因此，在人类疫苗接种方案中通常使用的单剂量或低疫苗剂量下，CpG / TLR9相互作用参与质粒DNA的免疫原性。这些结果表明TLR9信号传导途径参与质粒疫苗接种的功效。因此，在开发或改善用于治疗人类感染的疫苗方面应继续关注。

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