Bacillus Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T-Cell Responses in Infants: A Post Hoc Analysis of a Randomized Controlled Trial

Bacillus Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T-Cell Responses in Infants: A Post Hoc Analysis of a Randomized Controlled Trial.

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Item Type: Article
Official URL: https://doi.org/10.1164/rccm.202108-1892OC
Journal or Publication Title: American Journal of Respiratory and Critical Care Medicine
Volume: 205
Number: 7
Page Range: pp. 830-841
Date: 1 April 2022
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1164/rccm.202108-1892OC
ISSN: 1073-449X
Date Deposited: 08 Jan 2023 23:09
Abstract:

Rationale: Scar formation following bacillus Calmette-Guérin (BCG) vaccination has been associated with lower all-cause mortality; the relation between scar and mycobacteria-specific protection against tuberculosis is debated. Objectives: To evaluate the association between BCG skin reaction and mycobacteria-specific immune responses. Methods: A post hoc analysis was done among 214 infants in Australia randomized to vaccination with one of three BCG vaccine strains (BCG-Denmark, BCG-Japan, or BCG-Russia) given at birth or BCG-Denmark given at 2 months of age. Measurements and Main Results: BCG skin reaction size and characteristics 10 weeks after vaccination were related to the in vitro mycobacteria-specific immune responses measured in stimulated whole blood. The size and characteristics of the skin reaction correlated positively with in vitro immune responses, even after adjusting for BCG vaccine strain and age at vaccination. Specifically, the reaction size and characteristics correlated with the proportion of mycobacteria-specific polyfunctional CD4+ T cells after stimulation with BCG and PPD and, to a lesser extent, after stimulation with Mycobacterium tuberculosis or Mycobacterium ulcerans. A similar correlation was observed with concentrations of IFN-γ, IL-2, tumor necrosis factor, and IL-13 in the supernatant after stimulation with BCG, PPD, and M. tuberculosis and to some degree for the proportions of mycobacteria-specific polyfunctional CD8+ T cells and CD107+ cytotoxic cells. Conclusions: BCG skin reaction correlated with the magnitude of mycobacteria-specific T-cell responses. As T-cell responses play a key role in defense against mycobacteria, the relationship between BCG scar formation and protection against tuberculosis should be revisited. This may also extend to the need for BCG revaccination in scar-negative individuals.Clinical trial registered with www.australianclinicaltrials.gov.au/clinical-trial-registries (ACTRN12608000227392).

Keywords: BCG vaccine (Mycobacterium bovis); cellular immunity; randomized controlled trial; scar; tuberculosis.

Creators:
Creators
Email
Pittet, Laure F.
UNSPECIFIED
Fritschi, Nora
UNSPECIFIED
Tebruegge, Marc
UNSPECIFIED
Dutta, Binita
UNSPECIFIED
Donath, Susan
UNSPECIFIED
Messina, Nicole L.
UNSPECIFIED
Casalaz, Dan
UNSPECIFIED
Hanekom, Willem A.
UNSPECIFIED
Britton, Warwick J.
UNSPECIFIED
Robins-Browne, Roy
UNSPECIFIED
Curtis, Nigel
UNSPECIFIED
Ritz, Nicole
UNSPECIFIED
Last Modified: 08 Jan 2023 23:09
URI: https://eprints.centenary.org.au/id/eprint/1332

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