Since 2014, NIAID’s Centers of Excellence for Translational Research (CETR) have advanced discovery and preclinical development of new or improved medical countermeasures for emerging and re-emerging infectious diseases.
Through the new notice of funding opportunity (NOFO) Centers of Excellence for Translational Research (CETR) (U19, Clinical Trial Not Allowed), NIAID seeks applications from single institutions or consortia of institutions ready to generate, validate, and advance medical countermeasures (MCMs) against a select list of bacteria or fungi with known or emerging resistance to current therapies.
Each center will be organized around a theme focused on preclinical development or use of MCMs or technologies that target specified pathogens to translate research results into product development. Successful applicants must propose three or more research projects plus an administrative core, and may propose up to three scientific cores.
Targeted Pathogens
To start, know that your application must prioritize one or more of the antimicrobial resistant (AMR) pathogens below.
Bacteria
- Acinetobacter baumannii
- Campylobacter spp.
- Clostridioides difficile
- Enterobacter spp.
- Enterococcus spp.
- Escherichia coli
- Klebsiella pneumoniae
- Neisseria gonorrhoeae
- Non-tuberculous mycobacteria (NTM)
- Nontyphoidal Salmonella spp.
- Pseudomonas aeruginosa
- Salmonella enterica serovar Typhi
- Shigella spp.
- Staphylococcus aureus
- Streptococcus pneumoniae
Fungi
- Aspergillus fumigatus
- Candida spp., in particular C. auris
Though experiments with nonvirulent forms of these pathogens are allowed, you must focus on the virulent form.
Research Directions
The CETR program aims to develop MCMs that are effective against a variety of pathogens and toxins, technologies that can be widely applied to improve classes of products, and platforms that can reduce the time and cost of creating new products. To that end, your proposed research projects should focus on therapeutics, immunotherapeutics, vaccines, vaccine technologies, or in vitro diagnostics for the targeted pathogens.
Therapeutics
For AMR bacteria, applications should focus on therapeutic discovery in the lead optimization phase with existing lead candidates to support progression through pivotal nonclinical studies required for entry into clinical trials. For AMR fungal pathogens listed above, earlier lead discovery efforts are of interest.
Therapeutic candidates of interest include small molecule, biotherapeutic, monoclonal antibody, or phage candidates to be used as monotherapy, in combination with other drugs, or as adjunctive therapy. Candidates with broad-spectrum activity are encouraged, though you may also pursue therapeutic candidates with a narrow spectrum that target high-priority pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern.
Vaccines
Vaccines provide an important tool to combat infectious disease, yet the preclinical and clinical pipelines for vaccine candidates against the bacterial and fungal pathogens remain limited. This NOFO will support both antigen identification and development of vaccines (including immunoprophylactics) against one or more of the AMR pathogens. Monovalent, multivalent, or broadly protective vaccines may also be considered.
Related identification and validation of antigen targets and immunogen design should focus on systems vaccinology approaches and technologies including multi-omics approaches, structural biology, and computational modeling and prediction that elucidate host responses.
Diagnostics
This initiative will support coupled development of integrated, sensitive, culture-independent, pathogen identification testing systems with a phenotypic antibiotic or antifungal susceptibility testing system.
All diagnostics applications should be supported by sufficient proof-of-concept data to establish feasibility and reproducibility and should eventually exceed performance specifications of currently available instruments and systems for reduced turnaround time, breadth of antibiotic or anti-fungal test panels, and test performance. Additionally, applications should adequately describe design and development planning of instrument systems (e.g., assay and hardware prototype development, consumables development, sample preparation, sample processing, system integration, software development, manufacturing, and diagnostic validation).
Cores for Support
You must propose an Administrative Core, which will manage, coordinate, and supervise all Center activities. The Administrative Core will include a Scientific Advisory Board (SAB) that will participate in the development and management of the CETR and corresponding activities. Do not propose or contact any SAB members before an award is made (i.e., when applying).
Optionally, you can create up to three scientific cores, which would provide resources or facilities that are essential for the activities of two or more of your research projects. Scientific Cores are intended to only serve the needs of Center project researchers and they may not conduct research independent of the Center’s research projects.
Nonresponsive Elements
NIAID will consider applications that contain the research projects including the following to be nonresponsive and not review them:
- Therapeutic projects targeting AMR bacterial pathogens focused on basic discovery (e.g., target identification)
- Viral pathogens
- Bacterial strains: Mycobacterium tuberculosis, Group A/B Streptococcus, Bordetella pertussis, and Mycoplasma genitalium
- Clinical trials (all phases)
- Solely focused upon repurposing an FDA-approved drug
- Development of surveillance or detection technologies
- Activities other than translational activities towards the development of therapeutic, vaccine, or diagnostic countermeasures
Also, take note: Your application must include a “Product Development Strategy” attachment, and within that attachment you must describe Milestones and Product Development Plans. Only applications solely proposing early translational studies in fungal pathogens are exempt from this requirement.
Tie It All Together
Recall that your CETR application must be arranged around a central theme. The NOFO provides examples, such as:
- Developing new approaches for a known pathogen target (e.g., gyrase, cell wall) to include broad-spectrum therapeutics with extended activity against more than one AMR pathogen.
- Developing a monoclonal antibody, phage, or other technology approach to counter pathogen resistance.
- Developing faster phenotypic antibacterial susceptibility test (AST) characterization for better antibiotic stewardship.
Find additional examples of possible themes in the NOFO, as well as more thorough descriptions of translational research activities.
Administrative Details
Application budgets are not expected to exceed $5 million in annual direct costs and must reflect the actual research needs. The scope of the proposed project should determine the project period. The maximum project period is 5 years.
This NOFO has a single application due date: April 29, 2024, at 5 p.m. local time of the applicant organization.
Direct scientific or research-related questions to Dr. Candace Kerr at candace.kerr@nih.gov or 301-761-6257. For review-related inquiries, contact Dr. Caitlin Brennan at caitlin.brennan2@nih.gov or 301-761-7792 or Dr. Lindsey Pujanandez at lindsey.pujanandez@nih.gov or 301-761-7830.