Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.
NB: Council approval does not guarantee that a concept will become an initiative.
Table of Contents
- Long-Acting Drug Delivery Systems for ART Optimization in HIV-1 Infected Children
- Advancing Biomarker Discovery and Novel Point-of-Care Diagnostics for Active TB Disease Detection in HIV-1 Infected and Exposed Children
- HIV/HBV Co-Infection: Research To Advance HBV Cure
- Novel RNAs in Virology (Including HIV) and Immune Regulation: Basic Science and Therapeutic Discovery
For the published request for applications, see the November 20, 2018 Guide announcement, Long-Acting Drug Delivery Systems for ART Optimization in HIV-1 Infected Children (R61/R33 Clinical Trial Not Allowed)
Advancing Biomarker Discovery and Novel Point-of-Care Diagnostics for Active TB Disease Detection in HIV-1 Infected and Exposed Children
Request for Applications—proposed FY 2020 initiative
Contact: Patrick Jean-Philippe
Objective: To advance non-sputum-based tuberculosis (TB) diagnostics in HIV-1 infected and exposed uninfected children by promoting discovery and validation of novel TB biomarkers or development/optimization and early validation of novel TB diagnostic technologies for improved, simplified, rapid, and decentralized diagnosis of TB disease in these populations.
Description: The following activities are considered responsive:
- Those aimed at new biomarker discovery on non-sputum-based matrices and early evaluation of their performance characteristics in well-characterized cohorts or bio-banked samples for detection of TB disease in children
- Biomarker discovery activities are expected to include, but not be limited to:
- Host RNA transcript expression profile, proteomics (hosts or pathogen derived)
- Mycobacterium tuberculosis (Mtb)-specific antibody functional profiling (FcR binding, effector function, glycosylation pattern)
- Immune cells profiling
- Other biomarkers (e.g., extracellular vesicles/exosomes)
- Discovery activities involving more than one biomarker type are highly encouraged
- Development/optimization and early evaluation of novel ultrasensitive detection tools for novel or existing Mtb or host response-based biomarkers
- Evaluation of discriminatory ability along the spectrum of TB disease (microbiologically confirmed TB, clinically-diagnosed TB, latent/incipient TB) and not TB, including, when feasible, potentially confounding conditions (receipt vs. non-receipt of Bacillus Calmette-Guérin, non-tuberculous mycobacteria, pneumonia, and other respiratory diseases) is encouraged
- Eligible matrices include serum, urine, stools, or other non-sputum matrices (e.g., exhaled air)
- Target populations/age groups are HIV-infected or -exposed young children less than five years with diagnostic evaluation for TB disease in established prospective cohorts or well characterized stored samples from such cohorts
- Proposed biomarker/diagnostic technologies that can be developed as point-of-care tools
Industry partnership is encouraged.
The following are nonresponsive and will not be reviewed:
- Evaluation of sputum or other respiratory sample-based (e.g., gastric, nasopharyngeal aspirates) biomarkers or tests including molecular or microbiologic/culture-based tests
- Initiation of late-phase prospective evaluation of new TB diagnostics in children (i.e., large studies powered to provide evidence of diagnostic accuracy for the assay). However, such studies, if already existing, can be used as a source of samples.
- Validation of tests already approved/endorsed for use in that population (e.g., Xpert Ultra, urine lipoarabinomannan)
- Cohorts/samples that do not include HIV-infected children and children less than five years
For the published program announcement with set-aside funds, see the November 29, 2018 Guide announcement, Research to Advance HBV Cure: HIV/HBV Co-Infection and HBV Mono-infection (R01 Clinical Trial Not Allowed).
Novel RNAs in Virology (Including HIV) and Immune Regulation: Basic Science and Therapeutic Discovery
Program Announcement—proposed FY 2020 initiative
Contact: Lillian Kuo
Objective: The scientific objective is to support innovative basic research aimed at discovering and characterizing novel biologically active viral and/or host RNAs involved in virology (including HIV biology) and immune regulation. The program will also support discovery of novel functions of previously identified viral or host RNAs. These objectives include investigating the utility of these novel cellular or viral RNAs as drug targets through proof-of-concept studies.
Recent advances in RNA sequencing technologies have revealed a myriad of novel biologically active RNA species (e.g., lncRNAs, vaultRNAs, circRNAs, snoRNAs, piRNAs, rRNAs, YRNAs, tRNA fragments, and many others). In addition to intracellular activity, these novel RNA species may also have functional activity in the extracellular milieu where these extracellular RNAs (exRNAs) are selectively packaged into extracellular vesicles (exosomes) and/or bound to RNA-binding proteins or lipids.
These novel RNA species are hypothesized to have multiple functional roles and biological activities in basic biochemistry, molecular virology, cell biology, and regulating both innate and adaptive immune responses. Leveraging innovative basic RNA biology will ultimately open new opportunities for discovering or designing novel therapeutic interventions. The scientific objectives are to 1) support basic research on novel RNA species or novel functions of known RNAs, regulating viral infection or innate and/or adaptive immune pathways and 2) enable exploratory studies for identifying novel viral or cellular RNA targets for the discovery or design of interventions.
Description: This initiative will support exploratory research ranging from early RNA discovery and fundamental RNA biochemistry extending to the discovery or design of interventions. The focus is on novel viral and/or host cellular RNA species or new biological activities of previously identified RNAs with regulatory functions or biological activity in virology, host cell biology, innate and adaptive immune signaling pathways, immune regulation, and/or immunopathogenesis.
The initiative will support high-risk, high-reward, exploratory, and innovative research that may include but is not limited to:
- Basic research on the fundamental mechanisms of novel viral and/or host intra- or extracellular RNAs in regulating virus replication, immunopathogenesis, infection-associated expression patterns, virus latency, and/or persistence
- Basic research in defining either roles of novel RNAs or novel functions of known RNAs in regulating innate or adaptive immunity and inflammation
- Structural biology of novel RNAs in viral infections and immunity
- Discovery and validation of the potential utility of novel RNAs as biomarkers
- Therapeutic approaches using or targeting novel RNAs
- Developing novel RNA inhibitors and mimics as therapeutic targets