Protective efficacy of an attenuated Mtb ΔLprG vaccine in mice.

PLoS pathogens (2020-12-15)
Amanda J Martinot, Eryn Blass, Jingyou Yu, Malika Aid, Shant H Mahrokhian, Sara B Cohen, Courtney R Plumlee, Rafael A Larocca, Noman Siddiqi, Shoko Wakabayashi, Michelle Gardner, Rebecca Audette, Anne Devorak, Kevin B Urdahl, Eric J Rubin, Dan H Barouch

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.

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MILLIPLEX® Mouse High Sensitivity T Cell Panel - Immunology Multiplex Assay, Simultaneous analyze low levels of cytokine and chemokine biomarker with the High Sensitivity Bead-Based Multiplex Assays using the Luminex technology, in mouse serum, plasma and cell culture samples.
MILLIPLEX® Mouse Cytokine/Chemokine Magnetic Bead Panel - Premixed 32 Plex - Immunology Multiplex Assay, Simultaneously analyze multiple cytokine and chemokine biomarkers with Bead-Based Multiplex Assays using the Luminex technology, in mouse serum, plasma and cell culture samples.
Collagenase from Clostridium histolyticum, suitable for release of physiologically active rat hepatocytes, Type IV, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid