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首页> 外文期刊>Vaccine >Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction.
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Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction.

机译：3M-052的疫苗佐剂活性：咪唑喹啉，设计用于无需系统性细胞因子诱导的局部活性。

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The human Toll-like receptors (TLRs) are a family of receptors, which sense the presence of various structural elements of pathogens and damaged or effete components in the host. As they do so, they activate two critical arms of host defense, the rapid innate immune response and an adaptive immune response. The innate immune response is typified by the generation of Th1 cytokines, chemokines and type 1 interferons. As such, agonists for the TLRs have potential as antiviral and anticancer therapeutics. They are also well suited to function as vaccine adjuvants. 3M imidazoquinoline (IRM) molecules were the first synthetic small molecules identified as TLR agonists and can affect their biological activities through TLR7, TLR8, or both. The breadth of therapeutic opportunities for this family of molecules can require formulations tailored to the specific application. One consideration is specific formulations to avoid a systemic distribution of these TLR agonists and resulting cytokine storm-like effects on the host. 3M-052 is an IRM bearing a C18 lipid moiety and designed for slow dissemination from the site of application. In the present study 3M-052 has been evaluated for its in vitro TLR activity and for its efficacy as a vaccine adjuvant using a recombinant hemagglutinin from H1N1 A/Puerto Rico/8/34. Given subcutaneously, 3M-052 drives a strong Th1 response to hemagglutinin and serum neutralization of viable H1N1 A/Puerto Rico/8/34 virus in the absence of circulating TNF alpha or the induction of Th1 cytokines.
机译：人类Toll样受体（TLR）是一类受体，可感知病原体的各种结构元素以及宿主中受损或有效成分的存在。当他们这样做时，它们激活了宿主防御的两个关键臂，即快速的先天免疫反应和适应性免疫反应。先天性免疫反应的特征是Th1细胞因子，趋化因子和1型干扰素的产生。因此，TLR的激动剂具有抗病毒和抗癌治疗的潜力。它们也非常适合用作疫苗佐剂。 3M咪唑并喹啉（IRM）分子是第一个被鉴定为TLR激动剂的合成小分子，可通过TLR7和/或TLR8影响它们的生物学活性。该分子家族的治疗机会的广度可能需要针对特定​​应用量身定制的制剂。一个考虑因素是避免这些TLR激动剂的系统分布以及对宿主产生的细胞因子风暴样效应的特定制剂。 3M-052是带有C18脂质部分的IRM，设计用于从应用部位缓慢传播。在本研究中，已使用来自H1N1 A / Puerto Rico / 8/34的重组血凝素评估了3M-052的体外TLR活性及其作为疫苗佐剂的功效。皮下给予3M-052在没有循环TNFα或Th1细胞因子诱导的情况下，对血凝素和活H1N1 A / Puerto Rico / 8/34病毒的血清中和产生强烈的Th1反应。

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