• Sascha Wilk Michelsen, Bolette Soborg, Else Marie Agger, Lars Jorge Diaz, Soren Tetens Hoff, Anders Koch, Hans Christian Florian Sorensen, Peter Andersen, Jan Wohlfahrt, and Mads Melbye.
• Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Electronic address: swm@ssi.dk.
• Vaccine. 2016 Nov 21; 34 (48): 5975-5983.

BackgroundHuman immune responses to latent Mycobacterium tuberculosis (Mtb) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI antigens were associated with subsequent reduced risk of progression to TB.MethodsWe conducted a population-based cohort study in East Greenland (2012-2014) including individuals aged 5-31years. A personal identifier allowed follow-up in national registers including the TB notification register. Mtb infection was defined by a positive Quantiferon test. Immune responses to LTBI antigens were assessed by whole blood antigen stimulation and interferon gamma measurement.ResultsAmong 978 participants, 67 previously had TB. LTBI antigen (Rv1284, Rv2659, Rv2660c) immune response prevalence was 18%, 50%, 2% among Mtb-infected and 7%, 40%, 4% among non-infected (Quantiferon negative) participants. Among 911 participants without prior notified TB, 31 were notified with TB during study follow-up. Immune responses to LTBI antigens were not associated with reduced risk of subsequent TB; Rv1284 HR 0.92 (95%CI 0.28-3.04), Rv2659 HR 1.05 (95%CI 0.51-2.13), Rv2660c HR 3.06 (95%CI 0.70-13.37).ConclusionIn this large population-based study, human immune responses to selected LTBI antigens were not found to be strongly associated with reduced risk of subsequent TB.Copyright © 2016 Elsevier Ltd. All rights reserved.

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