Open AccessProtective efficacy of an attenuated Mtb ΔLprG vaccine in mice
Author(s) -
Amanda J. Martinot,
Eryn Blass,
Jingyou Yu,
Malika Aïd,
Shant H. Mahrokhian,
Sara Cohen,
Courtney R. Plumlee,
Rafael A. Larocca,
Noman Siddiqi,
Shoko Wakabayashi,
Michelle Gardner,
Rebecca E Audette,
Anne Devorak,
Kevin B. Urdahl,
Eric J. Rubín,
Dan H. Barouch
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009096
Subject(s) - immunology , mycobacterium tuberculosis , tuberculosis vaccines , vaccination , immune system , medicine , mycobacterium bovis , tuberculosis , attenuated vaccine , cytokine , vaccine efficacy , virology , biology , virulence , gene , biochemistry , pathology
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.