Erova Tatiana E, Rosenzweig Jason A, Sha Jian, Suarez Giovanni, Sierra Johanna C, Kirtley Michelle L, van Lier Christina J, Telepnev Maxim V, Motin Vladimir L, Chopra Ashok K
Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Clin Vaccine Immunol. 2013 Feb;20(2):227-38. doi: 10.1128/CVI.00597-12. Epub 2012 Dec 12.
Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1(-) strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1(-) mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1(-) CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains.
由鼠疫耶尔森菌引起的鼠疫表现为腺鼠疫、败血症型鼠疫和肺鼠疫。尽管美国食品药品监督管理局最近批准了左氧氟沙星，但尚无获批的针对鼠疫的人用疫苗。鼠疫耶尔森菌的荚膜抗原F1和低钙应答V抗原（LcrV）是很好的疫苗候选物；然而，针对F1和LcrV的免疫反应无法为鼠疫耶尔森菌F1（-）菌株或携带LcrV变体的菌株提供保护，这是一个重大问题。在此，我们表明，将感染鼠疫杆菌并用左氧氟沙星救治的大鼠的超免疫血清进行被动转移，可保护未感染的动物免受肺鼠疫感染。此外，在蛋白质印迹分析中，野生型（WT）鼠疫耶尔森菌CO92的10至12条蛋白带与上述超免疫血清发生反应。基于质谱分析，其中四种蛋白被鉴定为附着侵袭位点（Ail/OmpX）、纤溶酶原激活蛋白酶（Pla）、外膜蛋白A（OmpA）和F1。克隆了编码这些蛋白的基因，并从大肠杆菌中纯化重组蛋白用于免疫，然后在腺鼠疫和肺鼠疫模型中用F1（-）突变体或WT CO92攻击小鼠和大鼠。尽管当用F1（-）CO92菌株攻击时，针对Ail和OmpA的抗体可保护小鼠免受腺鼠疫感染，但Pla抗体可保护免受肺鼠疫感染。在大鼠模型中，针对Ail的抗体仅在WT CO92攻击后对肺鼠疫有保护作用。总之，将鼠疫耶尔森菌外膜蛋白添加到新一代重组疫苗中可对多种鼠疫耶尔森菌菌株提供保护。
