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

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

Fingerprint

Mycobacterium bovis
Mycobacterium tuberculosis
Capsules
Vaccination
Detergents
Growth
BCG Vaccine
Interleukin-17
Starvation
Transcriptome
Interferons
Polysaccharides
Tuberculosis
Vaccines
Spleen
Bacteria
T-Lymphocytes
Lung
Antibodies

Keywords

  • BCG
  • capsule
  • Mycobacterium tuberculosis
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

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

In: Journal of Infectious Diseases, Vol. 214, No. 3, 01.08.2016, p. 426-437.

Research output: Contribution to journalArticle

Prados-Rosales, Rafael ; Carreño, Leandro J. ; Weinrick, Brian ; Batista-Gonzalez, Ana ; Glatman-Freedman, Aarona ; Xu, Jiayong ; Chan, John ; Jacobs, William R. ; Porcelli, Steven A. ; Casadevall, Arturo. / 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. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 3. pp. 426-437.
@article{874f3e65114c4d5fb67136c48e92d07c,
title = "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",
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, capsule, Mycobacterium tuberculosis, vaccine",
author = "Rafael Prados-Rosales and Carre{\~n}o, {Leandro J.} and Brian Weinrick and Ana Batista-Gonzalez and Aarona Glatman-Freedman and Jiayong Xu and John Chan and Jacobs, {William R.} and Porcelli, {Steven A.} and Arturo Casadevall",
year = "2016",
month = "8",
day = "1",
doi = "10.1093/infdis/jiw153",
language = "English (US)",
volume = "214",
pages = "426--437",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - 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

AU - Prados-Rosales, Rafael

AU - Carreño, Leandro J.

AU - Weinrick, Brian

AU - Batista-Gonzalez, Ana

AU - Glatman-Freedman, Aarona

AU - Xu, Jiayong

AU - Chan, John

AU - Jacobs, William R.

AU - Porcelli, Steven A.

AU - Casadevall, Arturo

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - BCG

KW - capsule

KW - Mycobacterium tuberculosis

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=84981172521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981172521&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiw153

DO - 10.1093/infdis/jiw153

M3 - Article

VL - 214

SP - 426

EP - 437

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -