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

Rafael Prados-Rosales, Leandro J. Carreño, Brian Weinrick, Ana Batista-Gonzalez, Aarona Glatman-Freedman, Jiayong Xu, John Chan, William R. Jacobs, Steven A. Porcelli, Arturo Casadevall

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)426-437
Number of pages12
JournalJournal of Infectious Diseases
Volume214
Issue number3
DOIs
StatePublished - Aug 1 2016

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Keywords

  • BCG
  • Mycobacterium tuberculosis
  • capsule
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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