Vaccine adjuvant activity of 3M-052: An imidazoquinoline designed for local activity without systemic cytokine induction
Vaccine adjuvant activity of 3M-052: An imidazoquinoline designed for local activity without systemic cytokine induction
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DOI：
10.1016/j.vaccine.2011.05.061
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发表时间：
2011-07-26
期刊：
影响因子：
5.5
通讯作者：
Wightman, Paul D.
中科院分区：
文献类型：
--
作者：
Smirnov, Dmitri;Schmidt, Joshua J.;Wightman, Paul D.
人Toll样受体（Toll like receptors，TLR）是一类能检测宿主体内病原体结构元件和受损或衰竭成分的受体。当它们这样做时，它们激活宿主防御的两个关键武器，快速先天免疫反应和适应性免疫反应。先天性免疫应答以Th 1细胞因子、趋化因子和1型干扰素的产生为代表。因此，TLR的激动剂具有作为抗病毒和抗癌治疗剂的潜力。它们也非常适合用作疫苗佐剂。3 M咪唑并喹啉（3 M imidazoquinoline，3 M）分子是第一个被鉴定为TLR激动剂的合成小分子，并且可以通过TLR 7影响其生物活性。TLR 8或两者。该分子家族的治疗机会的广度可能需要针对特定应用定制的制剂。一个考虑是特定的制剂，以避免这些TLR激动剂的全身分布和对宿主产生的细胞因子风暴样作用。3 M-052是一种带有C18脂质部分的脂质体，设计用于从应用部位缓慢传播。在本研究中，使用来自HI NI A/波多黎各/8/34的重组血凝素评价了3 M-052的体外TLR活性及其作为疫苗佐剂的有效性。皮下给药，在不存在循环TNF α或诱导Th 1细胞因子的情况下，3 M-052驱动对血凝素和活H1N1 A/波多黎各/8/34病毒的血清中和的强烈Th 1应答。(C)2011爱思唯尔有限公司保留所有权利。
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 HI NI 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. (C) 2011 Elsevier Ltd. All rights reserved.