There were an estimated 1.6 million deaths due to tuberculosis (TB) in 2021 (including 187,000 people with HIV and AIDS). Mycobacterium tuberculosis (M.tb) (a NIAID Category C pathogen), the causative agent of TB, is the 13th leading cause of death (globally) and has again taken the lead as the number one killer due to a single infectious agent after being second to SARS-CoV-2 during the COVID-19 pandemic. In 2021, an estimated 10.6 million people fell ill with TB worldwide: 6 million men, 3.4 million women and 1.2 million children. TB is present in all countries and age groups.

The Immune Mechanisms of Protection Against Mycobacterium tuberculosis Centers (IMPAc-TB) program is an initiative established by NIAID in 2019 to elucidate the immune responses needed to protect against infection with M.tb. The program also aims to develop a better understanding of various pathogenesis aspects of TB infection such as latent infection, and transition to active TB disease. To accomplish these objectives, multidisciplinary research teams at Harvard T.H. Chan School of Public Health, Boston and Seattle Children's Research Institute were selected to conduct immunological analyses of tissue-specific and systemic responses in small animals, non-human primates (NHPs), and humans to identify the key immune responses needed for protection against M.tb; identify immunologic targets that can be used to improve TB vaccine strategies; determine the impact of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) and nontuberculous mycobacteria (NTM) infections on relevant immune responses to M.tb infection or TB vaccines; and identify how bacterial immune evasion mechanisms subvert immune responses to M.tb. This Research Topic will provide Center Objectives and Goals as well as some data that have been generated since execution of the three IMPAc-TB contracts.

In this Research Topic, we discuss important questions including:
• What are the mediators of the complex immune responses required to prevent M.tb infection or active TB disease?
• What are the common protective correlates of immunity against M.tb in escalating preclinical animal models of TB?
• How does NTM exposure affect the rational design and development of candidate vaccines that generate robust levels of durable, protective immunity against TB?
• What is the role of Systems Immunology in the context of investigating immune correlates of protection against M.tb?
• Why is it important to develop standardized reagents and standard operating procedures to profile immune responses in preclinical and human experimental medicine TB studies?
• Are transcriptional signatures predictive?
• What benefits are afforded by including the guinea pig model in the TB preclinical vaccine evaluation pipeline?
• How to manage data across consortiums generating large datasets?

The Topic Editors [RC, SF, WB, JF] declare that they are supported by the NIH on this IMPAc-TB collaboration.

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