Protection against heterologous Burkholderia pseudomallei strains by dendritic cell immunization.
Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative bacterium which can cause either chronic infections or acute lethal sepsis in infected individuals. The disease is endemic in Southeast Asia and northern Australia, but little is known about the mechanisms of protective immunity to the bacterium. In this study, we have developed a procedure to utilize dendritic cells in combination with CpG oligodeoxynucleotides as a vaccine delivery vector to induce protective immune responses to various strains of B. pseudomallei. Our results show that strong cell-mediated immune responses were generated, while antibody responses, although low, were detectable. Upon virulent challenge with B. pseudomallei strain K96243, NCTC 4845, or 576, animals immunized with dendritic cells that were pulsed with heat-killed K96243 and matured in the presence of CpG 1826 showed significant levels of protection. These results show that a vaccine strategy that actively targets dendritic cells can evoke protective immune responses.
Elvin
Stephen J
SJ
Biomedical Sciences, Dstl Porton Down, Salisbury SP4 0JQ, United Kingdom. SJElvin@dstl.gov.uk
Healey
Gareth D
GD
Westwood
Angie
A
Knight
Stella C
SC
Eyles
James E
JE
Williamson
E Diane
ED
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016957:Burkholderia pseudomallei / Q000276:immunology; D015331:Cohort Studies; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007114:Immunization; D008554:Melioidosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides
D000907:Antibodies, Bacterial; C423449:CpG ODN 1826; D009838:Oligodeoxyribonucleotides; D004247:DNA