Pulmonary MTBVAC vaccination induces immune signatures previously correlated with prevention of tuberculosis infection

Cell Rep Med. 2021 Jan 19;2(1):100187. doi: 10.1016/j.xcrm.2020.100187.


To fight tuberculosis, better vaccination strategies are needed. Live attenuated Mycobacterium tuberculosis-derived vaccine, MTBVAC, is a promising candidate in the pipeline, proven to be safe and immunogenic in humans so far. Independent studies have shown that pulmonary mucosal delivery of Bacillus Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine available today, confers superior protection over standard intradermal immunization. Here we demonstrate that mucosal MTBVAC is well tolerated, eliciting polyfunctional T helper type 17 cells, interleukin-10, and immunoglobulins in the airway and yielding a broader antigenic profile than BCG in rhesus macaques. Beyond our previous work, we show that local immunoglobulins, induced by MTBVAC and BCG, bind to M. tuberculosis and enhance pathogen uptake. Furthermore, after pulmonary vaccination, but not M. tuberculosis infection, local T cells expressed high levels of mucosal homing and tissue residency markers. Our data show that pulmonary MTBVAC administration has the potential to enhance its efficacy and justifies further exploration of mucosal vaccination strategies in preclinical efficacy studies.

Keywords: BCG; MTBVAC; Th1/Th17; antibodies; immune correlates; mucosal immunity; non-human primate; tissue-resident memory; tuberculosis; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • BCG Vaccine / administration & dosage*
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / immunology
  • Female
  • Gene Expression Regulation
  • Immunity, Mucosal*
  • Injections, Intradermal
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Lung / drug effects
  • Lung / immunology
  • Lung / microbiology
  • Macaca mulatta
  • Male
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / microbiology
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / microbiology
  • Th1 Cells / immunology
  • Th1 Cells / microbiology
  • Th17 Cells / immunology
  • Th17 Cells / microbiology
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • BCG Vaccine
  • Il17a protein, mouse
  • Interleukin-17
  • MTBVAC vaccine
  • Tuberculosis Vaccines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10