title: In search of a new paradigm for protective immunity to TB.
abstract: Clinical trials of vaccines against Mycobacterium tuberculosis are well under way and results are starting to come in. Some of these results are not so encouraging, as exemplified by the latest Aeras-422 and MVA85A trials. Other than empirically determining whether a vaccine reduces the number of cases of active tuberculosis, which is a daunting prospect given the chronic nature of the disease, we have no way of assessing vaccine efficacy. Therefore, investigators seek to identify biomarkers that predict vaccine efficacy. Historically, focus has been on the production of interferon-γ by CD4(+) T cells, but this has not been a useful correlate of vaccine-induced protection. In this Opinion article, we discuss recent advances in our understanding of the immune control of M. tuberculosis and how this knowledge could be used for vaccine design and evaluation.
authors.affiliation: 1] Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. [2] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal and the ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Nunes-Alves
authors.affiliation: 1] Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. [2] Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Booty
authors.affiliation: 1] Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. [2] Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Carpenter
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Jayaraman
authors.affiliation: 1] Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. [2] Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Alissa C
authors.initials: AC
authors.lastname: Rothchild
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000382:microbiology* / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D015415:Biomarkers; D032581:Tuberculosis Vaccines