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Biosafety Level 2 Model of Pneumonic Plague and Protection Studies with F1 and Psa

机译：F1和Psa肺炎鼠疫的生物安全2级模型和保护研究

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Attenuated Yersinia pestis pgm strains, such as KIM5, lack the siderophore yersiniabactin. Strain KIM5 does not induce significant pneumonia when delivered intranasally. In this study, mice were found to develop pneumonia after intranasal challenge with strain KIM5 when they were injected intraperitoneally with iron dextran, though not with iron sulfate. KIM5-infected mice treated daily with 4 mg iron dextran died in 3 days with severe pneumonia. Pneumonia was less severe if 4 mg iron dextran was administered only once before infection. The best-studied experimental vaccine against plague currently consists of the Yersinia pestis capsular antigen F1 and the type 3 secreted protein LcrV. The F1 antigen was shown to be protective against KIM5 infections in mice administered iron dextran doses leading to light or severe pneumonia, supporting the use of an iron dextran-treated model of pneumonic plague. Since F1 has been reported to be incompletely protective in some primates, and bacterial isolates lacking F1 are still virulent, there has been considerable interest in identifying additional protective subunit immunogens. Here we showed that the highly conserved Psa fimbriae of Y. pestis (also called pH 6 antigen) are expressed in murine organs after infection through the respiratory tract. Studies with iron dextran-treated mice showed that vaccination with the Psa fimbrial protein together with an adjuvant afforded incomplete but significant protection in the mouse model described. Therefore, further investigations to fully characterize the protective properties of the Psa fimbriae are warranted.
机译：减毒的鼠疫耶尔森氏菌pgm 菌株，例如KIM5，缺少铁载体耶尔森菌素。鼻内给药时，菌株KIM5不会引起明显的肺炎。在这项研究中，当小鼠腹膜内注射右旋糖酐铁，但未注射硫酸铁时，发现它们在用KIM5菌株鼻内攻击后出现肺炎。每天用4 mg葡聚糖铁治疗的感染KIM5的小鼠在3天内因严重的肺炎死亡。如果在感染前仅给予4 mg右旋糖酐铁一次，则肺炎的严重程度将降低。目前研究最好的抗鼠疫实验疫苗包括鼠疫耶尔森菌荚膜抗原F1和3型分泌蛋白LcrV。在给予右旋糖铁剂量导致轻度或重度肺炎的小鼠中，F1抗原对KIM5感染具有保护作用，支持使用右旋糖酐铁治疗的鼠疫鼠疫模型。据报道，由于F1在某些灵长类动物中的保护作用不完全，而缺乏F1的细菌分离株仍然具有毒性，因此人们对鉴定其他保护性亚基免疫原具有浓厚兴趣。在这里，我们显示了 Y的高度保守的Psa菌毛。鼠疫通过呼吸道感染后在鼠类器官中表达瘟疫（也称为pH 6抗原）。用右旋糖酐铁治疗的小鼠的研究表明，用Psa纤维蛋白和佐剂进行疫苗接种可在上述小鼠模型中提供不完全但有效的保护。因此，有必要进行进一步的研究以充分表征Psa菌毛的保护特性。

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