In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-14), p. e1009096-
Abstract:
Bacille Calmette-Guerin (BCG), an attenuated whole cell vaccine based on Mycobacterium bovis , is the only licensed vaccine against Mycobacterium tuberculosis ( Mtb ), but its efficacy is suboptimal and it fails to protect against pulmonary tuberculosis. We previously reported that Mtb lacking the virulence genes lprG and rv1410c ( ΔLprG) was highly attenuated in immune deficient mice. In this study, we show that attenuated ΔLprG Mtb protects C57BL/6J, Balb/cJ, and C3HeB/FeJ mice against Mtb challenge and is as attenuated as BCG in SCID mice. In C3HeB/FeJ mice, ΔLprG vaccination resulted in innate peripheral cytokine production and induced high polyclonal PPD-specific cytokine-secreting CD4 + T lymphocytes in peripheral blood. The ΔLprG vaccine afforded protective efficacy in the lungs of C3H/FeJ mice following both H37Rv and Erdman aerosolized Mtb challenges. Vaccine efficacy correlated with antigen-specific PD-1-negative CD4 + T lymphocytes as well as with serum IL-17 levels after vaccination. We hypothesize that induction of Th17 cells in lung is critical for vaccine protection, and we show a serum cytokine biomarker for IL-17 shortly after vaccination may predict protective efficacy.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009096
DOI:
10.1371/journal.ppat.1009096.g001
DOI:
10.1371/journal.ppat.1009096.g002
DOI:
10.1371/journal.ppat.1009096.g003
DOI:
10.1371/journal.ppat.1009096.g004
DOI:
10.1371/journal.ppat.1009096.g005
DOI:
10.1371/journal.ppat.1009096.g006
DOI:
10.1371/journal.ppat.1009096.g007
DOI:
10.1371/journal.ppat.1009096.g008
DOI:
10.1371/journal.ppat.1009096.s001
DOI:
10.1371/journal.ppat.1009096.s002
DOI:
10.1371/journal.ppat.1009096.s003
DOI:
10.1371/journal.ppat.1009096.s004
DOI:
10.1371/journal.ppat.1009096.s005
DOI:
10.1371/journal.ppat.1009096.s006
DOI:
10.1371/journal.ppat.1009096.s007
DOI:
10.1371/journal.ppat.1009096.s008
DOI:
10.1371/journal.ppat.1009096.s009
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2205412-1