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Infection and Immunity, August 2007, p. 4173-4180, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00404-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Identification of a LolC Homologue in Burkholderia pseudomallei, a Novel Protective Antigen for Melioidosis{triangledown}

David N. Harland,1 Karen Chu,2 Ashraful Haque,2 Michelle Nelson,1 Nicola J. Walker,1 Mitali Sarkar-Tyson,1 Timothy P. Atkins,1 Benjamin Moore,3 Katherine A. Brown,3 Gregory Bancroft,2 Richard W. Titball,1,2* and Helen S. Atkins1

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom,1 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom,2 Division of Cell and Molecular Biology, CMMI, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom3

Received 18 March 2007/ Returned for modification 12 April 2007/ Accepted 7 May 2007

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.

* Corresponding author. Present address: Department of Molecular Microbiology, School of Biosciences, Geoffrey Pope Building, University of Exeter, Exeter EX4 4QD, United Kingdom. Phone: 44 392-269157. Fax: 44 392-263700. E-mail: r.w.titball{at}exeter.ac.uk

{triangledown} Published ahead of print on 21 May 2007.

Editor: D. L. Burns

Infection and Immunity, August 2007, p. 4173-4180, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00404-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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