A micro-sterile inflammation array as an adjuvant for influenza vaccines.

A micro-sterile inflammation array as an adjuvant for influenza vaccines.
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DOI:
10.1038/ncomms5447
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发表时间:
2014-07-18
影响因子:
16.6
通讯作者:
Wu, Mei X.
Wu, Mei X.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang, Ji;Shah, Dilip;Chen, Xinyuan;Anderson, R. Rox;Wu, Mei X.

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皮肤疫苗接种急需佐剂。在这里,我们报道在接种部位诱导的微无菌炎症可以增强动物模型对流感疫苗的免疫反应。在皮内注射疫苗之前,用手持式非烧蚀分式激光短暂照射接种部位,这在皮肤中产生一系列自我修复的微热区(MTZs)。MTZ中的垂死细胞发出“危险”信号,吸引大量抗原呈递细胞,特别是每个MTZ周围的浆细胞样树突状细胞(pDCs),形成一个微无菌炎症阵列。pDCs在佐剂性中的关键作用是通过系统消耗pDCs、局部应用TNF-α抑制剂或IFN调节因子7 (IRF7)的零突变后免疫力的显著丧失来确定的。与引起持续炎症和皮肤损伤的传统佐剂相比,微无菌炎症增强了流感疫苗的功效,同时减少了不良反应。
There is an urgent need of adjuvants for cutaneous vaccination. Here we report that micro-sterile inflammation induced at inoculation sites can augment immune responses to influenza vaccines in animal models. The inoculation site is briefly illuminated with a handheld, non-ablative fractional laser before the vaccine is intradermally administered, which creates an array of self-healing microthermal zones (MTZs) in the skin. The dying cells in the MTZs send “danger” signals that attract a large number of antigen-presenting cells, in particular, plasmacytoid dendritic cells (pDCs) around each MTZ forming a micro-sterile inflammation array. A pivotal role for pDCs in the adjuvanticity is ascertained by significant abrogation of the immunity after systemic depletion of pDCs, local application of a TNF-α inhibitor, or null mutation of IFN regulatory factor7 (IRF7). In contrast to conventional adjuvants that cause persistent inflammation and skin lesions, micro-sterile inflammation enhances efficacy of influenza vaccines, yet with diminished adverse effects.
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