Concepts represent early planning stages for program announcements, requests for applications, notices of special interest, 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
Fiscal Year (FY) 2022 Concepts
FY 2023 Concepts
- Systems Biology for Infectious Diseases (SysBioID)
- Accelerating Group A Streptococcus Vaccine Discovery
- Fundamental Research To Understand the Mechanisms of Neurotropic Virus-Mediated Disease
- Identification and Characterization of Persistence Mechanisms of Protozoan Pathogens
- Host Immunity and Novel Immunization Strategies for Clostridioides difficile
Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern
For the published request for applications, see the July 9, 2021 Guide announcement, Emergency Awards: Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern (U19 Clinical Trial Not Allowed).
Systems Biology for Infectious Diseases (SysBioID)
Request for Applications—proposed FY 2023 initiative
Contact: Reed Shabman
Objective: To support research that employs a systems biology approach across pathogens to rapidly transform large datasets into predictive models that complement and guide in vitro, in vivo, and clinical studies, with the ultimate goals of predicting disease severity, predicting responses to vaccines and therapeutics, and identifying candidate targets for interventions.
Description: The Systems Biology for Infectious Diseases (SysBioID) Centers address complex questions across pathogens with high-throughput (HTP) generation, analysis, and computational modeling of large datasets (e.g., ‘omics’). The proposed FY 2023 SysBioID initiative will continue to support this cross-disciplinary holistic approach and seek to more rapidly transform large datasets and metadata into predictive models of patient disease susceptibility, onset, and severity across bacterial, viral, fungal, and parasitic pathogens. Multi-component projects will be supported to 1) integrate clinical data, metadata, and large ‘omics’ datasets (genomics, proteomics, metabolomics, lipidomics, etc.) in the context of an infectious disease to model outcome and inform development of prevention and treatment candidates or strategies; 2) obtain mechanistic insight from laboratory studies to validate established models; and 3) iterate and refine those established models to improve their predictive accuracy. Projects will also perform secondary analyses on existing datasets and validate findings with laboratory studies. In addition, SysBioID Centers will be expected to develop or improve innovative experimental methods, technologies, bioinformatics and computational tools, machine learning software, and statistical inference methods. These can be used by the Centers and the broad infectious diseases community for systems level data analysis.
Program outputs include 1) integrated data sets, maps of molecular networks of host-pathogen interactions, and computational predictive models of infectious diseases; 2) new and enhanced computational algorithms, methods, and tools; and 3) protocols for state-of-the-art high throughput technologies. All data, reagents, tools, and other resources generated under this initiative must be rapidly disseminated to the broad scientific community with no restrictions on their use. Examples of research areas include but are not limited to:
- Determination of host/pathogen molecular networks and predictive models which identify biosignatures that predict risk, severity, and response to therapeutic intervention of an infectious disease.
- Determination of molecular networks and predictive models focused on genetic and epigenetic (e.g., miRNA or methylation-regulated) pathways regulating host responses to pathogen infection or therapeutic intervention.
- Incorporation of non-traditional data sources (e.g., wearables, mobility data) with novel computational, mathematical, and statistical algorithms and methods, including artificial intelligence and machine learning approaches to predict disease risk and severity.
Accelerating Group A Streptococcus Vaccine Discovery
Request for Applications—proposed FY 2023 initiative
Contact: Xin-Xing Gu
Objective: To support the discovery and evaluation of new targets, immune mechanisms, and vaccine approaches to prevent Group A Streptococcus (GAS) infection.
Description: The goal of this solicitation is to promote basic and translational research to advance GAS vaccine discovery. Research projects may include but are not limited to: innovative antigen/epitope discovery strategies with emphasis on approaches that provide broad protection; structure-based immunogen design; evaluation of novel GAS vaccine candidates in preclinical models with detailed immunologic assessments in blood and tissues; studies to identify correlates of protection; and research to improve or develop new animal models that more accurately represent human disease and immunity.
Fundamental Research To Understand the Mechanisms of Neurotropic Virus-Mediated Disease
Request for Applications—proposed FY 2023 initiative
Contact: Lesley Dupuy
Objective: To promote basic research to better understand the mechanisms underlying viral invasion of the central nervous system (CNS), virus- and/or host immune-mediated neuropathogenesis, and the associated clinical manifestations for emerging and re-emerging neurotropic viruses.
Description: This initiative will support fundamental research into mechanisms that lead to neuropathogenesis after acute viral infection of the CNS. To fill this important knowledge gap, this initiative will focus on less-studied emerging and re-emerging neurotropic viruses for which there are currently no approved vaccines or therapeutics such as non-polio enteroviruses (e.g., EV-D68, EV-A71), flaviviruses (e.g., WNV, POWV, DTV), alphaviruses (e.g., EEEV, VEEV, CHIKV), bunyaviruses (e.g., RVFV, LACV), and paramyxoviruses (e.g., NiV, HeV). This initiative would exclude well-studied neurotropic viruses, many of which have approved vaccines or therapeutics, such as herpesviruses, orthomyxoviruses, rhabdoviruses, retroviruses, poliovirus, and certain paramyxoviruses (e.g., MV, MuV). The scope of the studies to be performed under this initiative would include, but not necessarily be limited to, the following:
- Identifying cellular host factors and mechanisms of cellular tropism of viral infection
- Route and mechanisms of invasion of the CNS (e.g., blood-brain barrier, blood-CSF barrier)
- Role of direct viral factors and host immune response/host cell signaling in inflammation of the CNS
- Developing and refining in vitro and in vivo models for viral neuropathogenesis
Identification and Characterization of Persistence Mechanisms of Protozoan Pathogens
Request for Applications—proposed FY 2023 initiative
Contact: John Pesce
Objective: To expand our understanding of protozoan parasite persistence mechanisms and provide research tools and strategies to enable identification and credentialing of novel treatments for persistent protozoan pathogens.
Description: Many protozoan parasites establish long-lived infections, sometimes even in the face of seemingly appropriate therapy, yet the mechanisms of such persistence remain largely unknown and untapped as targets of potential intervention(s). This initiative will support basic and preclinical research to characterize persister stages in selected protozoan infections (e.g., relapsing malaria, Chagas Disease, leishmaniasis, toxoplasmosis, and trichomoniasis). For each pathogen, the following research areas will be prioritized:
- Identifying environmental signals or triggers for protozoan entry into or exit from metabolically quiescent states
- Identifying the mechanisms for entry into, maintenance of, and exit from metabolically quiescent states
- Developing appropriate in vitro models of persister infection
- Identifying potential druggable targets during quiescent states or approaches to break dormancy, thus potentially increasing the efficacy of available therapeutics
Host Immunity and Novel Immunization Strategies for Clostridioides difficile
Request for Applications—proposed FY 2023 initiative
Contact: Ryan Ranallo
Objective: To explore host adaptive immune responses to Clostridioides difficile with the goal of producing next-generation vaccine candidates.
Description: This initiative solicits applications from single or consortia institutions that focus on understanding host immunity and developing novel immunization strategies aimed at protecting individuals from infection with the nosocomial pathogen, Clostridioides difficile. The formation of new multidisciplinary collaborative research teams that focus on key knowledge gaps relating to host immunity to C. difficile is a critical component of this effort, as it will enable the rational design of next-generation vaccine candidates to bolster the C. difficile vaccine pipeline.
This program will support the formation of integrative teams and multiproject programs to conduct an in-depth exploration of host adaptive immune responses to C. difficile infection (CDI). Investigators will probe the role of systemic and mucosal immunity to CDI and determine the impact of the gut microbiome on the host immune response to infection. In addition to identifying new protective antigens for inclusion into novel preclinical vaccine candidates, each team will consider the impact of antigenic diversity on protection against CDI. The use of clinical data and samples (e.g., serum, stool, or peripheral cells) from high-risk cohorts (e.g., intensive care unit patients, long-term care residents, or oncology patients) will be leveraged to identify correlates of protection and to characterize cell-mediated immunity and immunological memory. The use of preclinical animal models that parallel the pathophysiology of the disease in at-risk humans will be encouraged, as will vaccine and adjuvant technology that are specifically designed to stimulate local (gut) mucosal immune responses.
Responsive U19 projects will focus on host immunity and vaccine development. Examples of research areas of interest include but are not limited to:
- Clinical Research: Cohort studies focused on gathering new insights from at-risk populations (e.g., >65 years, frequent antibiotic use, comorbidities).
- Immunology Research: Studies focused on key knowledge gaps (e.g., systemic vs. mucosal immunity) and correlates of protection.
- Microbial Pathogenesis Research: Studies focused on aspects of C. difficile pathogenesis and life cycle that lead to the discovery of novel protective antigens.
- Microbiome and Host Immunity Research: Studies focused on the impact of the gut microbiota on host immunity to CDI.
- Novel Vaccine Platforms and Improved Model Systems: Studies focused on testing preclinical vaccine candidates in animal models that parallel the pathophysiology of the disease.