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Infect. Immun. doi:10.1128/IAI.00404-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

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

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK; Division of Cell and Molecular Biology, CMMI, Flowers Building, Imperial College London, London SW7 2AZ, UK

* To whom correspondence should be addressed. Email: rwtitball{at}dstl.gov.uk.


   Abstract

Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing the disease, Burkholderia pseudomallei, is also considered a bioterrorism agent and, as yet, there is no licensed vaccine for preventing the infection. In this study, we have evaluated selected proteins (LolC, PotF and OppA) of the ABC systems of B. pseudomallei as candidate vaccine antigens. Non-membrane regions of the B. pseudomallei proteins were expressed and purified from E. coli, then evaluated as vaccine candidates in an established mouse model of B. pseudomallei infection. When delivered with the MPL+TDM 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 administered with ISCOMs 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.







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