title: Protective effect of DNA immunization against mycobacterial infection is associated with the early emergence of interferon-gamma (IFN-gamma)-secreting lymphocytes.
abstract: The development of more effective anti-tuberculosis (TB) vaccines would contribute to the global control of TB. Understanding the activated/memory T cell response to mycobacterial infection and identifying immunological correlates of protective immunity will facilitate the design and assessment of new candidate vaccines. Therefore, we investigated the kinetics of the CD4+ T cell response and IFN-gamma production in an intravenous challenge model of Mycobacterium bovis bacille Calmette-Guérin (BCG) before and after DNA immunization. Activated/memory CD4+ T cells, defined as CD44hiCD45RBlo, expanded following infection, peaking at 3-4 weeks, and decreased as the bacterial load fell. Activated/memory CD4+ T cells were the major source of IFN-gamma and the level of antigen-specific IFN-gamma-secreting lymphocytes, detected by ELISPOT, paralleled the changes in bacterial load. To examine the effects of a DNA vaccine, we immunized mice with a plasmid expressing the mycobacterial secreted antigen 85B (Ag85B). This led to a significant reduction in mycobacteria in the liver, spleen and lung. This protective effect was associated with the rapid emergence of antigen-specific IFN-gamma-secreting lymphocytes which were detected earlier, at day 4, and at higher levels than in infected animals immunized with a control vector. This early and increased response of IFN-gamma-secreting T cells may serve as a correlate of protective immunity for anti-TB vaccines.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia.
authors.forename: A T
authors.initials: AT
authors.lastname: Kamath
authors.forename: N L
authors.initials: NL
authors.lastname: Groat
authors.forename: A G
authors.initials: AG
authors.lastname: Bean
authors.forename: W J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D004247:DNA / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D013154:Spleen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014376:Tuberculosis / Q000517:prevention & control*; D019444:Vaccines, DNA
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D019444:Vaccines, DNA; D007371:Interferon-gamma; D004247:DNA