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J Infect Dis. 2016 Aug 1;214(3):426-37. doi: 10.1093/infdis/jiw153. Epub 2016 Apr 18.

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.

Author information

1
Department of Microbiology and Immunology CIC bioGUNE, Bizkaia Technology Park, Derio, Spain.
2
Department of Microbiology and Immunology Millennium Institute on Immunology and Immunotherapy, Programa Disciplinario de Inmunologia, Facultad de Medicina, Universidad de Chile, Santiago.
3
Department of Microbiology and Immunology Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York.
4
Department of Microbiology and Immunology.
5
Department of Pediatrics, and Department of Family and Community Medicine, New York Medical College, Valhalla, New York.
6
Department of Microbiology and Immunology Department of Medicine.
7
Department of Microbiology and Immunology Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Erratum in

Abstract

BACKGROUND:

Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.

METHODS:

We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis

RESULTS:

Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence.

CONCLUSIONS:

The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies.

KEYWORDS:

BCG; Mycobacterium tuberculosis; capsule; vaccine

PMID:
27234419
PMCID:
PMC4936643
DOI:
10.1093/infdis/jiw153
[Indexed for MEDLINE]
Free PMC Article

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