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

Author:

Harland David N.1,Chu Karen2,Haque Ashraful2,Nelson Michelle1,Walker Nicola J.1,Sarkar-Tyson Mitali1,Atkins Timothy P.1,Moore Benjamin3,Brown Katherine A.3,Bancroft Gregory2,Titball Richard W.12,Atkins Helen S.1

Affiliation:

1. Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom

2. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom

3. Division of Cell and Molecular Biology, CMMI, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom

Abstract

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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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