Vaccination with plasmid DNA expressing the Yersinia pestis capsular protein F1 protects mice against plague.

Vaccination with plasmid DNA expressing the Yersinia pestis capsular protein F1 protects mice against plague.
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接种表达鼠疫耶尔森氏菌荚膜蛋白 F1 的质粒 DNA 可以保护小鼠免受鼠疫侵害。

DOI:
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发表时间:
2003
影响因子:
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通讯作者:
Sara B. Cohen
Sara B. Cohen
中科院分区:
医学4区
文献类型:
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作者:
H. Grosfeld;T. Bino;Y. Flashner;R. Ber;Emanuelle Mamroud;S. Lustig;B. Velan;A. Shafferman;Sara B. Cohen

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1荚膜蛋白(F1)被认为是鼠疫杆菌特有的重要但非必需的毒力因子(Welkos et al., 1995)。用F1蛋白免疫已被证明可保护小鼠免受野生型鼠疫杆菌的皮下攻击(Andrews等人,1996年),含有F1和V抗原的联合配方可保护小鼠免受空气传播感染(Williamson等人,1997年)。这种蛋白质也与人类的保护性免疫反应有关。观察到遗传免疫能够引起保护性免疫,促进了新一代疫苗的开发。编码F1蛋白的caf1基因以前被用作DNA疫苗。在这项研究中,发现近亲繁殖的小鼠没有反应,而近亲繁殖的小鼠则有较弱的遗忘反应(Brandler et al., 1998)。基因疫苗的出现和对DNA疫苗反应程度调节因素的信息积累使我们重新审视基于F1抗原的基因疫苗。在这里,我们比较了三种携带不同细胞定位信号的F1 DNA衍生物,并证明了一种可能靶向细胞质表达的遗传衍生物诱导了有效的抗体反应,并赋予了对高剂量感染性鼠疫杆菌的保护。
The fraction 1 capsular protein (F1) is considered an important but not essential virulence factor unique to Y. pestis (Welkos et al., 1995). Immunization with the F1 protein has been shown to protect mice against subcutaneous challenge with wild type Y. pestis (Andrews et al., 1996) and a combined formulation containing F1 and V antigen confers protection against airborne infection (Williamson et al., 1997). The protein has been associated with eliciting protective immune response in humans as well. The observation that genetic immunization is able to elicit a protective immunity has fostered a new generation in vaccine development. The caf1 gene, which codes for the F1 protein, was previously used as DNA vaccine. In this study inbred mice were found to be non responsive, and outbred mice responded by a weak anamnestic response (Brandler et al., 1998). The advent in genetic vaccination and the accumulating information on factors modulating the extent of response to DNA vaccines led us to re-examine genetic vaccination based on F1 antigen. Here we compare three F1 DNA derivatives carrying different signals for cellular localization and demonstrate that one such genetic derivative, which presumably targets expression to the cytosol induces an effective antibody response and confers protection against high doses of infective Y. pestis.