title: Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis.
abstract: The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations. One possible explanation for this variability is increased exposure of certain populations to non-tuberculous mycobacteria (NTM). This study used a murine model to determine the effect that exposure to NTM after BCG vaccination had on the efficacy of BCG against aerosol Mycobacterium tuberculosis challenge. The effects of administering live Mycobacterium avium (MA) by an oral route and killed MA by a systemic route on BCG-induced protection were evaluated. CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy. BCG efficacy was enhanced by exposure to killed MA administered by a systemic route; T helper 1 and T helper 17 responses were associated with increased protection. BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection. These findings demonstrate that exposure to NTM can induce opposite effects on BCG efficacy depending on route of exposure and viability of NTM. A reproducible model of NTM exposure would be valuable in the evaluation of novel TB vaccine candidates.
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: hpoyntz@malaghan.org.nz.
authors.forename: Hazel C
authors.initials: HC
authors.lastname: Poyntz
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: elena.stylianou@ndm.ox.ac.uk.
authors.forename: Elena
authors.initials: E
authors.lastname: Stylianou
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Kristin.griffiths@gmail.com.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Griffiths
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Leanne.marsay@ndm.ox.ac.uk.
authors.forename: Leanne
authors.initials: L
authors.lastname: Marsay
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: annacheckley@yahoo.com.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Checkley
authors.affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: Helen.mcshane@ndm.ox.ac.uk.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D015269:Mycobacterium avium Complex / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology / Q000494:pharmacology; D062690:Vaccines, Live, Unattenuated / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D001500:BCG Vaccine; D016207:Cytokines; D014613:Vaccines, Attenuated; D062690:Vaccines, Live, Unattenuated
keywords: Bacillus Calmette-Geurin; Mouse model; Mycobacterium avium; Non-tuberculous mycobacteria; Tuberculosis