A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell-mediated immunity, priming T cells specific for 2 type III secretion system proteins.
Burkholderia pseudomallei is the etiological agent of melioidosis, a serious human disease for which no vaccine is available. Immunization of susceptible BALB/c mice with the live attenuated mutant B. pseudomallei ilvI (referred to as "2D2") generated significant, although incomplete, immunity. Splenic B. pseudomallei-specific T cells, detected in immunized mice, proliferated and produced interferon-gamma in vitro in response to dead bacteria. Assessment of T cell antigen specificity indicated that subpopulations of B. pseudomallei-reactive T cells were responsive to BopE, a type III secretion system (TTSS) effector protein, and to a lesser extent to BipD, a TTSS translocator protein. Increased survival of severe combined immunodeficient mice adoptively transferred with T cells from immunized mice, compared with that of naive T cell recipients, demonstrated that immunization with 2D2 generated T cell-mediated immunity. CD4+ and CD8+ cell depletion studies demonstrated that CD4+ cells, but not CD8+ cells, mediated this protection in vivo. Thus, CD4+ T cells can mediate vaccine-induced immunity to experimental melioidosis.
Haque
Ashraful
A
London School of Hygiene and Tropical Medicine, London, United Kingdom. ashraful.haque@qimr.edu.au
Chu
Karen
K
Easton
Anna
A
Stevens
Mark P
MP
Galyov
Edouard E
EE
Atkins
Tim
T
Titball
Rick
R
Bancroft
Gregory J
GJ
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D019121:Burkholderia Infections / Q000276:immunology* / Q000517:prevention & control; D016957:Burkholderia pseudomallei / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000378:metabolism / Q000382:microbiology; D014774:Virulence
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007371:Interferon-gamma