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

被引:56
作者
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
[1] Def Sci & Technol Lab, Salisbury SP4 0JQ, Wilts, England
[2] London Sch Hyg & Trop Med, London WC1E 7HT, England
[3] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, CMMI, London SW7 2AZ, England
关键词
D O I
10.1128/IAI.00404-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Immoral 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.
引用
收藏
页码:4173 / 4180
页数:8
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