title: Quest for correlates of protection against tuberculosis.
abstract: A major impediment to tuberculosis (TB) vaccine development is the lack of reliable correlates of immune protection or biomarkers that would predict vaccine efficacy. Gamma interferon (IFN-γ) produced by CD4(+) T cells and, recently, multifunctional CD4(+) T cells secreting IFN-γ, tumor necrosis factor (TNF), and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune parameter, reflecting activity of a vaccine and potentially predicting protection. However, accumulating experimental evidence suggests that host resistance against Mycobacterium tuberculosis infection is independent of IFN-γ and TNF secretion from CD4(+) T cells. Furthermore, the booster vaccine MVA85A, despite generating a high level of multifunctional CD4(+) T cell response in the host, failed to confer enhanced protection in vaccinated subjects. These findings suggest the need for identifying reliable correlates of protection to determine the efficacy of TB vaccine candidates. This article focuses on alternative pathways that mediate M. tuberculosis control and their potential for serving as markers of protection. The review also discusses the significance of investigating the natural human immune response to M. tuberculosis to identify the correlates of protection in vaccination.
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Verma
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA salgampa@njms.rutgers.edu.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019444:Vaccines, DNA
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; D007376:Interleukin-2; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma