Immune Mechanisms of Protection Against Tuberculosis (IMPAc-TB) Center

Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases. NIAID supports a robust program in basic immunology that includes detailed analyses of human immune responses to pathogenic infections and/or vaccines. NIAID also has a key role in basic, translational and clinical studies to further the understanding of Mycobacterium tuberculosis infection and disease in people living with or without HIV. Furthermore, NIAID provides several resources to the scientific community including testing services of therapeutics, animal models, reagents for research to support biomedical drug, vaccines and diagnostics research. The NIAID Divisions of AIDS (DAIDS); Allergy Immunology and Transplantation (DAIT) and Microbiology and Infectious Diseases (DMID) have a joint requirement for the continued support of the Immune Mechanisms of Protection against Mycobacterium tuberculosis center (IMPAc-TB) program to accelerate TB vaccine development through characterization of protective tissue-specific and systemic immune responses that prevent or contain Mtb infection and the advancement of tools and resources to support TB vaccine development. The objective of the IMPAc-TB program renewal is to address these knowledge gaps and accelerate TB vaccine development by supporting research that further characterizes both tissue-specific and systemic protective immune responses, that prevent or contain Mtb infection, and furthers the advancement of tools and resources that facilitate TB vaccine development ( e.g ., biological models and in vitro systems, computational and modeling platforms). This program will continue to support the comprehensive understanding of protective immunity to Mtb and the impact of HIV/SIV infection on responses to Mtb infection and TB vaccines. This solicitation will require the use of human samples and/or clinical studies, at least one animal model, and computational data integration and modeling for cross-comparative analyses of the human and animal studies. These requirements are in alignment with NIH’s initiative to prioritize human-based research (NIH Funding Announcements to Align with NIH Initiative to Prioritize Human-based Research | Grants & Funding). In addition, investigators may consider using new approach methods (NAMS) such as organoid or other ex vivo systems to assess human immunity to Mtb or TB vaccines. This program will help identify signatures associated with risk or protection from disease/infection and identify and evaluate protective antigens/immune epitopes. The identification of immune epitopes within the IMPAc-TB program is complementary to the DAIT Immune Epitope Discovery programs, and NIAID Program will foster cross-collaborative activities. In addition, the initiative will support translation of knowledge gained about tissue-specific immune responses to advance vaccine approaches (including mucosal vaccine approaches). IMPAc-TB will support the refinement of fit-for-purpose animal models for testing vaccine candidates targeting different stages of TB disease and emerging technologies such as tissue-based models, and computational modeling for cross-species analyses. Clinical research will also be supported through clinical cohorts or clinical trials using novel vaccine candidates and will enable backtranslation to animal models. To facilitate cross-contract collaborative studies and activities, each contractor will set aside from their individual budget, $300,000/year in total costs starting in years two through five of the contracts. These funds will be used to support small-scale studies and/or other activities.  Do not propose cross-contract collaborative studies/activities in the proposal. The cross-contract collaborative studies will be proposed starting in year two of the contract by each IMPAc-TB contractor. The proposed cross-contract collaborative studies will be evaluated by NIH Program staff, the PI(s) of each IMPAc-TB contract, and the External Scientific Advisory Group (ESAG).  The final selection of the cross-contract collaborative study will be made by NIH. It is anticipated that two to three cost reimbursement, completion type contracts will be awarded with performance beginning about September 1, 2027. NIAID estimates that the average annual total cost (direct and indirect costs combined) for the entire program will be $10.5 million. However, it is anticipated that the total cost for each award may vary depending upon the scope of the project and the technical objectives and will be approximately $5 million total costs per year. The length of time for which funding is requested should be