title: Enhanced protective efficacy against Mycobacterium tuberculosis afforded by BCG prime-DNA boost regimen in an early challenge mouse model is associated with increased splenic interleukin-2-producing CD4 T-cell frequency post-vaccination.
abstract: The development of improved vaccines and vaccination strategies against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. Simple measurement of interferon-γ frequency or production per se does not provide adequate prediction of immune protection. In this study, we examined the relationship between T-cell immune responses and protective efficacy conferred by the heterologous vaccination strategy, bacillus Calmette-Guérin (BCG) prime-Ag85A DNA boost (B/D), in an early challenge mouse model of pulmonary tuberculosis. The results demonstrated that mice vaccinated with the B/D regimen had a significantly reduced bacillary load compared with BCG-vaccinated mice, and the reduction in colony-forming units was associated with decreased pathology and lower levels of inflammatory cytokines in the infected lungs. Further analysis of immunogenicity showed that the superior protection afforded by the B/D regimen was associated with significantly increased frequency of splenic interleukin-2 (IL-2) -producing CD4 T cells and increased IL-2 production when measured as integrated mean fluorescence intensity post-vaccination as well. These data suggest that measurement of elevated frequency of IL-2-producing CD4 T cells or IL-2 production in the spleens of vaccinated mice can predict vaccine efficacy, at least in the B/D strategy, and add to the accumulating body of evidence suggesting that BCG prime-boost strategies may be a useful approach to the control of M. tuberculosis infection.
authors: Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Han
authors: H
authors: Kang
authors: Qin
authors: Q
authors: Yuan
authors: Hui
authors: H
authors: Ma
authors: Zhi-Dong
authors: ZD
authors: Hu
authors: De-Ping
authors: DP
authors: Han
authors: Kang
authors: K
authors: Wu
authors: Douglas B
authors: DB
authors: Lowrie
authors: Xiao-Yong
authors: XY
authors: Fan
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007117:Immunization, Secondary; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2
keywords: DNA vaccine; Mycobacterium tuberculosis; interleukin-2; multifunctional T cell; prime-boost; protective immunity