Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, PO Box 875401, Tempe, AZ 85287-5401, United States.
Vaccine. 2010 Dec 16;29(2):274-82. doi: 10.1016/j.vaccine.2010.10.033. Epub 2010 Oct 24.
We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague.
我们评估了由减毒沙门氏菌菌株传递的鼠疫耶尔森氏菌抗原 HmuR、Psn 和 LcrV 的修饰形式对皮下或鼻腔内用鼠疫耶尔森氏菌 CO92 进行攻击的保护免疫应答的能力。LcrV196 是一种先前描述的截短蛋白，包括 LcrV 的 aa131-326，LcrV5214 已被修饰以替换与 TLR2 受体相互作用所需的五个关键氨基酸。Psn 是铁载体、耶尔森氏菌素和细菌素、杀虫素的外膜受体。用合成 Psn、LcrV196 或 LcrV5214 的沙门氏菌免疫的小鼠对各自的耶尔森氏菌抗原产生血清 IgG 应答，并对鼠疫耶尔森氏菌的肺炎性攻击具有保护作用。用合成 Psn 或 LcrV196 的沙门氏菌免疫足以提供对 bubonic 挑战的几乎完全保护，而用合成 LcrV5214 的菌株免疫则没有保护作用。用合成 HmuR 的沙门氏菌免疫，HmuR 是鼠疫耶尔森氏菌中血红素获取的外膜蛋白，免疫原性差，不能对任何一种挑战途径产生保护反应。这些发现表明，由沙门氏菌传递的 Psn 和 LcrV196 都能提供对 bubonic 和 pneumonic 鼠疫的保护。
