Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis.
Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis.
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DOI：
10.1371/journal.pone.0066614
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mizutani H
中科院分区：
文献类型：
--
作者：
Kitagawa H;Kawano M;Yamanaka K;Kakeda M;Tsuda K;Inada H;Yoneda M;Sakaguchi T;Nigi A;Nishimura K;Komada H;Tsurudome M;Yasutomi Y;Nosaka T;Mizutani H
特应性皮炎（AD）是一种难治性、复发性炎症性皮肤病。遗传因素、环境因素、先天免疫和获得性免疫、皮肤屏障功能等多种因素参与AD的发病。T -辅助性（Th） 2主导的免疫环境已被认为在阿尔茨海默病的急性期。抗原85B （Ag85B）是一个30 kda的分泌蛋白，在分枝杆菌中保守。Ag85B具有较强的th1型细胞因子诱导活性，有望改善过敏性疾病的Th2状况。为了在体内发挥Ag85B的功能，需要有效且侵入性较小的疫苗接种方法。最近，我们建立了一种新的功能性病毒载体；重组人副流感2型病毒载体（rhPIV2）：高表达、复制缺陷和非常低致病性的载体。在这项研究中，我们研究了rhPIV2在重复恶唑酮（OX）诱导的小鼠AD模型中表达Ag85B （rhPIV2/Ag85B）的效果。rhPIV2/Ag85B处理组小鼠耳肿胀、真皮细胞浸润和血清IgE水平均明显受到抑制，IFN-γ和IL-10 mRNA表达升高，IL-4、TNF-α和MIP-2 mRNA表达受到抑制。治疗后小鼠未出现组性及全身不良反应的临床症状。呼吸道上皮可有效捕获rhPIV2，无明显细胞毒性作用。这些结果表明，rhPIV2/Ag85B可能是控制过敏性疾病的有效治疗工具。
Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.
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影响因子：
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