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类鼻疽杆菌中LolC同源物的鉴定,一种类鼻疽病的新型保护性抗原。

Identification of a LolC homologue in Burkholderia pseudomallei, a novel protective antigen for melioidosis.

作者信息

Harland David N, Chu Karen, Haque Ashraful, Nelson Michelle, Walker Nicola J, Sarkar-Tyson Mitali, Atkins Timothy P, Moore Benjamin, Brown Katherine A, Bancroft Gregory, Titball Richard W, Atkins Helen S

机构信息

Department of Molecular Microbiology, School of Biosciences, Geoffrey Pope Building, University of Exeter, Exeter, United Kingdom.

出版信息

Infect Immun. 2007 Aug;75(8):4173-80. doi: 10.1128/IAI.00404-07. Epub 2007 May 21.

Abstract

Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing this disease, Burkholderia pseudomallei, is also considered a bioterrorism agent, and as yet there is no licensed vaccine for preventing B. pseudomallei infection. In this study, we evaluated selected proteins (LolC, PotF, and OppA) of the ATP-binding cassette systems of B. pseudomallei as candidate vaccine antigens. Nonmembrane regions of the B. pseudomallei proteins were expressed and purified from Escherichia coli and then evaluated as vaccine candidates in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the proteins stimulated antigen-specific humoral and cellular immune responses. Immunization with LolC or PotF protein domains afforded significant protection against a subsequent challenge with B. pseudomallei. The most promising vaccine candidate, LolC, provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also protected against a subsequent challenge with a heterologous strain of B. pseudomallei, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis.

摘要

类鼻疽是东南亚和热带澳大利亚地区一种新出现的人类疾病。引起这种疾病的细菌——类鼻疽伯克霍尔德菌,也被视为一种生物恐怖主义制剂,目前尚无预防类鼻疽伯克霍尔德菌感染的许可疫苗。在本研究中,我们评估了类鼻疽伯克霍尔德菌ATP结合盒系统的选定蛋白(LolC、PotF和OppA)作为候选疫苗抗原。类鼻疽伯克霍尔德菌蛋白的非膜区域从大肠杆菌中表达和纯化,然后在已建立的类鼻疽伯克霍尔德菌感染小鼠模型中作为候选疫苗进行评估。当与单磷酰脂质A - 海藻糖二分枝菌酸佐剂一起递送时,这些蛋白刺激了抗原特异性体液和细胞免疫反应。用LolC或PotF蛋白结构域免疫可对随后的类鼻疽伯克霍尔德菌攻击提供显著保护。最有前景的候选疫苗LolC与与CpG寡脱氧核苷酸10103复合的免疫刺激复合物一起给药时,提供了更高水平的保护。用LolC免疫还能抵御随后的异源类鼻疽伯克霍尔德菌菌株的攻击,证明了这种蛋白作为类鼻疽疫苗抗原的潜在效用。

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