Funding Opportunity Purpose
The purpose of this Funding Opportunity Announcement (FOA) is to invite applications for support of innovative clinical and preclinical/non-clinical research to improve our understanding of disease mechanisms in tuberculosis meningitis (TBM) and to improve therapy in the presence or absence of human immunodeficiency virus (HIV) co-infection.
Research Objectives and Scope
This FOA will support hypothesis-based clinical and preclinical/non-clinical research studies focused on: 1) Identifying pathogenic and immunopathogenic mechanisms in the context of CNS-TB in in vitro and appropriate animal models that impact TBM disease development, progression, and outcomes, as well as the effect of HIV co-infection on these mechanisms; 2) Assessing molecular targets in pathogenic and immunopathogenic mechanisms leading to discovery or confirmation of targets for HDT; and 3) Evaluating new/repurposed antimicrobial drugs and/or dosing of current antimicrobials that are optimized for TBM treatment for use in combinations to more rapidly clear the infection.
Research topics of interest on TBM pathogenesis and treatment in the presence or absence of HIV include, but are not limited to:
- Mechanisms of Mtb dissemination into the CNS including:
- Role of antigen-presenting cells, e.g., dendritic cells, and vascular endothelial cells
- Microbial factors involved in CNS penetration, localization and dissemination
- Role of microglia and other CNS-specific immune cells responding to/or infected by Mtb and HIV, and mechanisms for persistence and subsequent reactivation
- Mechanisms and mediators of dysregulation of signaling pathways of CNS immune cell responses involved in TBM pathogenesis with and without HIV infection, including evasion of host defenses and vascular and CNS cell damage
- Role of innate immune cell receptors (e.g., pattern-recognition receptors) in the cellular stress/damage mechanisms of TBM and CNS IRIS
- Determining promising targets for adjunctive TBM HDT, and testing specifically targeted host-directed agents in appropriate models
- Identification of candidates for improved diagnostics, indicators of disease severity, and prognostic biomarkers for treatment outcomes derived from immunopathogenic studies in animal models, and validation utilizing stored clinical samples
- Developing and testing antimicrobial drug regimens in appropriate TBM models, including new and repurposed agents and/ or optimized dosing of current anti-TB drugs
The following types of applications will not be supported through this FOA:
- Applications which propose clinical trials or the establishment of patient cohorts.
- Applications which focus solely on HIV.
- Applications primarily focused on cytokines/interleukins, chemokines, interferons, or eicosanoids as targets.
Eligibility
Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period
The scope of the proposed project should determine the project period. The maximum project period is 5 years.
Key Dates
Open Date (Earliest Submission Date): August 4, 2018.
Letter of Intent Due Date(s): Not Applicable
*Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Scientific Merit Review: October 2018
Advisory Council Review: January 2019
Earliest Start Date: April 2019
Deadline
Application Due Date(s)
September 4, 2018 by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.
