@article{TEXTUAL,
      recid = {14652},
      author = {Singh, Dhiraj K. and Ahmed, Mushtaq and Akter, Sadia and  Shivanna, Vinay and Bucşan, Allison N. and Mishra, Abhishek  and Golden, Nadia A. and Didier, Peter J. and Doyle, Lara  A. and Hall-Ursone, Shannan and Roy, Chad J. and Arora,  Garima and Dick, Edward J., Jr. and Jagannath, Chinnaswamy  and Mehra, Smriti and Khader, Shabaana A. and Kaushal,  Deepak},
      title = {Prevention of tuberculosis in cynomolgus macaques by an  attenuated <i>Mycobacterium tuberculosis</i>  vaccine candidate},
      journal = {Nature Communications},
      address = {2025-02-25},
      number = {TEXTUAL},
      abstract = {The need for novel vaccination strategies to control  tuberculosis (TB) is underscored by the limited and  variable efficacy of the currently licensed vaccine,  Bacille Calmette-Guerin (BCG). SigH is critical for  <i>Mycobacterium tuberculosis (Mtb)</i> to mitigate  oxidative stress, and in its absence <i>Mtb</i> is unable  to scavenge host oxidative/nitrosative bursts. The  <i>MtbΔsigH</i> (<i>ΔsigH</i>) isogenic mutant induces  signatures of the innate immunity in macrophages and  protects rhesus macaques from a lethal <i>Mtb  challenge</i>. To understand the immune mechanisms of  protection via mucosal vaccination with <i>ΔsigH</i>, we  employed the resistant cynomolgus macaque model; and our  results show that <i>ΔsigH</i> vaccination significantly  protects against lethal <i>Mtb</i> challenge in this  species. <i>ΔsigH</i>-vaccinated macaques are devoid of  granulomas and instead generate inducible bronchus  associated lymphoid structures, and robust antigen-specific  CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses,  driven by a hyper-immune, trained immunity-like phenotype  in host macrophages with enhanced antigen presentation.  Correlates of protection in <i>ΔsigH</i>-vaccinated  macaques include gene signatures of T cell activation, IFNG  production, including IFN-responsive, activated T cells,  concomitant with IFNG production, and suppression of  IDO<sup>+</sup> Type I IFN-responsive macrophage  recruitment. Thus, <i>ΔsigH</i> is a promising lead  candidate for further development as an antitubercular  vaccine.},
      url = {http://knowledge.uchicago.edu/record/14652},
}