Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 214, Issue 3, Pages 426-437Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw153
Keywords
BCG; vaccine; Mycobacterium tuberculosis; capsule
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Funding
- National Institutes of Health [5R01HL059842, 5R01AI033774, 5R37AI033142, 5R01AI052733, 1R21AI115091, P01AI063537, R01AI094745, R01AI093649]
- Bill and Melinda Gates Foundation [OPP1070514]
- Spanish Ministry of Economy and Competitiveness
- Pew Latin American Fellows Program
- Bill and Melinda Gates Foundation [OPP1070514] Funding Source: Bill and Melinda Gates Foundation
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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. 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.
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