Respiratory syncytial virus infection of gene gun vaccinated mice induces Th2-driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein
Respiratory syncytial virus infection of gene gun vaccinated mice induces Th2-driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein
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DOI：
10.1016/s0264-410x(00)00344-3
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发表时间：
2000-12-08
期刊：
影响因子：
5.5
通讯作者：
Taylor, G
中科院分区：
文献类型：
--
作者：
Bembridge, GP;Rodriguez, N;Taylor, G
用2.5杯编码呼吸道合胞病毒(RSV)融合蛋白(F)的DNA沉淀在金微珠上，对两次免疫小鼠产生完全保护作用。相反，编码RSV附着物(G)蛋白的DNA免疫可显著降低感染后的病毒载量，但不能提供完全保护。基因枪注射DNA-F可诱导Th2偏向的免疫应答，而IL-2、IL-12或干扰素-γ的共传递不能调节这种偏向的免疫应答。类似地，DNA-G基因枪注射启动了Th2反应。因此，所有基因枪免疫的小鼠都产生了以Th2为主的肺免疫反应，其特征是在RSV攻击后产生IL-4和IL-5，几乎没有干扰素-γ。对攻击后5天的支气管肺泡灌洗液(BAL)细胞的分析表明，接种疫苗组的炎症细胞数量仅是对照动物的两倍。尽管肺淋巴细胞有很强的Th2细胞因子偏向和CD4(+)T细胞的主要募集，但在攻击后，没有明显的肺嗜酸性粒细胞反应(范围从BAL的2%到7%)。相反，接种了对照质粒组的小鼠的BAL中含有的嗜酸性粒细胞明显多于其他组。(C)2000爱思唯尔科学有限公司。保留所有权利。
Complete protection against respiratory syncytial virus (RSV) infection was induced in mice vaccinated on two occasions with 2.5 mug of DNA, encoding the fusion (F) protein of RSV, precipitated onto gold microbeads. In contrast, immunisation with DNA encoding the attachment (G) protein of RSV resulted in a significant reduction in viral load following infection, but did not afford complete protection. Gene gun delivery of DNA-F elicited a T helper-2 (Th2) biased immune response that could not be modulated by the co-delivery of plasmids encoding IL-2, IL-12 or IFN gamma. Similarly gene gun delivery of DNA-G primed a Th2 response. Thus, all gene gun vaccinated mice produced a predominant Th2 biased pulmonary immune response characterised by the production of IL-4 and IL-5 with little IFN gamma following RSV challenge. Analysis of bronchoalveolar lavage (BAL) cells, 5 days post challenge, indicated that there was only a two-fold increase in the number of inflammatory cells in vaccinated compared with control animals. Despite the strong Th2 cytokine bias of lung lymphocytes and the predominant recruitment of CD4(+) T cells, following challenge, there was not a marked pulmonary eosinophilic response (range from 2 to 7% of BAL). In contrast, the BAL from mice vaccinated with control plasmid contained significantly more eosinophils than any other group. (C) 2000 Elsevier Science Ltd. All rights reserved.