The purpose of this Funding Opportunity Announcement (FOA) is to support innovative studies to identify and understand the immune responses that mediate protection from Mycobacterium tuberculosis (Mtb) infection or progression to active tuberculosis (TB) disease. Such responses may be operative in mycobacterial infection, or following vaccination with Bacillus Calmette-Guérin (BCG) or investigational TB vaccines. Studies may focus on any stage of mycobacterial infection and may include HIV-infected or uninfected individuals. Research supported under this FOA should go beyond descriptive information currently known about Mtb infection, immune responses to TB vaccines, or immune modulation by non-tuberculous mycobacterial (NTM) infection, or by HIV/AIDS. Applications are sought that include characterization of the timing, anatomical location, and contribution to disease outcome, of mucosal and/or systemic immune responses to mycobacterial infection and/or vaccination. This research is expected to advance understanding of immune mechanisms in Mtb infection/vaccination and contribute to the advancement of new TB vaccines, including in populations also infected with HIV.
Objectives and Scope
This program will support innovative studies to identify and understand the immune responses that mediate protection from Mtb infection or progression to active TB disease. Such responses may be operative in mycobacterial infection, or following vaccination with BCG or investigational TB vaccines. Studies may focus on any stage of mycobacterial infection and may include HIV-infected and/or uninfected individuals.
Examples of potential research areas of interest include, but are not limited to:
- Elucidation of mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms, throughout the course of mycobacterial infection/disease or vaccination and how HIV infection may shift this balance.
- Analysis of clinical trial samples evaluating TB vaccine candidates to identify immune correlates of protection from Mtb infection, or risk of TB disease progression.
- Preclinical evaluation of novel TB vaccine candidates with concurrent in-depth immunologic analyses.
- Analysis of innate immune pathways and mechanisms in response to Mtb infection and/or TB progression, including trained immunity and the effect on downstream activation of adaptive immune responses.
- Application of systems immunology approaches for analysis of systemic and tissue-specific responses to Mtb, NTM, BCG or investigational TB vaccines.
- Immune mechanisms that result in direct killing or elimination of Mtb.
- Effect of prior/chronic exposure to mycobacterial species (including NTM) or BCG vaccination on subsequent immune responses to Mtb infection, TB reactivation, investigational TB vaccine efficacy or disease recurrence in HIV-infected or -uninfected individuals.
- Analysis of the role of non-classical T cells in immunity to Mtb infection.
- Determination of the contribution of the humoral immune response to protection against Mtb.
- Identification of processes associated with mobilization/homing and maintenance of protective immune cells in the lung.
- Investigation of the timing/nature of immune responses leading to protection against disseminated TB in children to determine whether activity of BCG can be modified to protect adults against Mtb infection or disease.
- Development of novel functional assays to monitor protective immune responses in humans.
Applications proposing any of the following research topics will NOT be supported under this FOA:
- Projects focusing solely on mechanisms of TB pathogenesis that do not include analysis of immune parameters.
- Projects focusing primarily on reagent or animal model development.
- Projects addressing Tuberculosis-Associated Immune Reconstitution Syndrome (TB-IRIS).
For more information, or to apply, visit the call webpage.