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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.

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.

Pubmed ID: 27234419 RIS Download

Mesh terms: Adjuvants, Immunologic | Animals | Antibodies, Bacterial | BCG Vaccine | Bacterial Capsules | CD4-Positive T-Lymphocytes | Culture Media | Female | Gene Expression Profiling | Interferon-gamma | Interleukin-17 | Mice, Inbred C57BL | Mycobacterium bovis | Mycobacterium tuberculosis

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI033774
  • Agency: NIAID NIH HHS, Id: P01 AI063537
  • Agency: NHLBI NIH HHS, Id: R01 HL059842
  • Agency: NIAID NIH HHS, Id: R01 AI094745
  • Agency: NIAID NIH HHS, Id: R01 AI052733
  • Agency: NIAID NIH HHS, Id: R21 AI115091
  • Agency: NIAID NIH HHS, Id: R37 AI033142
  • Agency: NCI NIH HHS, Id: P30 CA013330
  • Agency: NIAID NIH HHS, Id: R01 AI093649

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