Selective delipidation of Mycobacterium bovis BCG enables direct pulmonary vaccination and enhances protection against Mycobacterium tuberculosis.
Alkanes
/ chemistry
Animals
BCG Vaccine
/ chemistry
Female
Inflammation Mediators
/ chemistry
Interleukin-17
/ metabolism
Lipid Metabolism
Lipids
/ chemistry
Lung
/ immunology
Mice
Mice, Inbred C57BL
Mycobacterium bovis
/ physiology
Mycobacterium tuberculosis
/ physiology
Tuberculosis, Pulmonary
/ immunology
Vaccination
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
31
08
2018
accepted:
27
01
2019
revised:
02
01
2019
pubmed:
20
2
2019
medline:
19
6
2019
entrez:
20
2
2019
Statut:
ppublish
Résumé
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the leading killer due to an infectious organism. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved against TB, however, its efficacy against pulmonary TB is poor. While BCG is currently inoculated intradermally, the natural route of M.tb infection is through the lung. Excessive lung pathology caused by pulmonary inoculation of BCG has prevented the use of this immunization route. Here, we show that selective chemical treatment of BCG with petroleum ether removes inflammatory lipids from the bacterial surface while keeping BCG viable. Pulmonary vaccination using this modified BCG attenuated inflammatory responses, prevented immunopathology of the lung, and significantly increased protection against M.tb infection in mice. We further directly linked IL-17A as the responsible contributor of improved immunity against M.tb infection. These results provide evidence that selective removal of cytotoxic lipids from the BCG surface attenuates inflammation and offers a safer and superior vaccine against TB causing less damage post-infectious challenge with M.tb.
Identifiants
pubmed: 30778118
doi: 10.1038/s41385-019-0148-2
pii: S1933-0219(22)00424-X
pmc: PMC6462255
mid: NIHMS1521048
doi:
Substances chimiques
Alkanes
0
BCG Vaccine
0
Inflammation Mediators
0
Interleukin-17
0
Lipids
0
naphtha
O3L624621X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
805-815Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001070
Pays : United States
Organisme : NIAID NIH HHS
ID : R00 AI073856
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI093570
Pays : United States
Organisme : NIAID NIH HHS
ID : K99 AI073856
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG051428
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM068412
Pays : United States
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