NIAID is updating its 2018 Strategic Plan for Tuberculosis Research and invites comments and suggestions from the scientific research community and stakeholders in a time-sensitive Request for Information (RFI): Inviting Comments and Suggestions on Updating the NIAID Strategic Plan for Tuberculosis Research.

The revised Strategic Plan is structured around five strategic priorities that capitalize on recent advances in the field; each critical to the development and evaluation of knowledge and tools needed to end tuberculosis (TB) globally.

The strategic priorities also identify research gaps that should be addressed and are as follows:

Improve fundamental knowledge of TB

• Improve the understanding of infection and disease spectrum caused by Mycobacterium tuberculosis (Mtb).
• Evaluate the dynamics and pathophysiology of TB disease in humans.
• Characterize immune responses and role of other host factors in Mtb infections.
• Determine factors that drive TB transmission.
• Understand the role of asymptomatic or subclinical TB in disease and transmission.
• Improve fundamental knowledge of the above in pediatric populations.

Advance research to improve diagnosis of TB

• Discover and validate novel TB biomarkers or biosignatures.
• Improve and develop accurate and rapid diagnostics, including point-of-care or near to point-of-care diagnostics.
• Improve diagnostics for extra-pulmonary TB.
• Improve TB diagnostics for pediatric populations and people living with HIV (PLWH).

Accelerate research to improve TB prevention

• Support design and development of vaccine candidates.
• Identify correlates of immune protection.
• Utilize TB Preventative Treatment (TPT) programs and modeling tools to predict transmission and apply preventative tools effectively.
• Discover, develop, and improve interventions to reduce TB transmission.

Support research to advance strategies to treat TB

• Discover, develop, and evaluate new and improved therapeutic interventions and combination regimens for pulmonary and extrapulmonary disease.
• Evaluate shorter treatment schedules for drug resistant and drug sensitive TB.
• Develop and advance new anti-TB drug candidates appropriate for use in HIV-associated TB and pediatric populations.
• Develop strategies to detect, minimize, and prevent post-TB lung disease and emergence of drug resistance.

Develop tools and resources to advance TB research

• Optimize or develop animal models that reflect human disease and are predictive of clinical outcomes.
• Develop, standardize, and share tools to facilitate product testing as well as resource and data/sample sharing.
• Leverage and expand the current clinical capacity of NIAID resources to test new therapeutic candidates, treatment regimens, diagnostics, and vaccine candidates in healthy and high-risk populations including pediatric populations, PLWH, and pregnant women.
• Promote cross-disciplinary research and support early investigators to expand the cadre of innovative TB researchers.
• Develop quantitative tools to assess treatment response and low bacillary burden in humans.
• Develop improved tools for tracking TB cases and outbreaks.
• Optimize coordination across U.S. government agencies, global stakeholders, and research funders.

Information Requested

Tell us your thoughts on the above framework as well as your views on the following topics in TB research:

• Significant research advances since 2018.
• Significant research gaps or barriers not identified in the strategic priorities above.
• Impact of COVID-19 pandemic on tuberculosis research.
• Emerging scientific advances or techniques that may accelerate research related to the strategic priorities identified above.
• Resources necessary to advance research in tuberculosis related to the strategic priorities above.

How to Submit a Response

Submit comments electronically on the RFI website by 11:59 p.m. on August 13, 2023.

Responses are voluntary. Please do not include any personally identifiable information or information you do not wish to make public. Do not include proprietary, classified, confidential, trade secrets, or other sensitive information with your response.

Direct all inquiries to NIAIDTBPlan@niaid.nih.gov.

Apply for research funds to identify interventional targets of early-stage Mycobacterium tuberculosis (Mtb) infections with and without HIV through the notice of funding opportunity (NOFO) Analyzing Early Events in TB and TB/HIV Infection for Interventional Targets (R01, Clinical Trial Not Allowed).

Research Objectives

The goal of this NOFO is to support mechanistic studies of early-stage Mtb infection in the airway and lungs with and without HIV to identify interventional targets for vaccine and host-directed therapies. Your proposed research should focus on mechanisms of Mtb-induced immune evasion/disruption of immunity-related cell functions and interactions among myeloid, lymphoid, and non-immune cells within the airway and lung tissue that determine disease progression versus cessation.

Your research should define the earliest specific reactions of diverse innate cells to the presence of Mtb in the lung and airway tissue and enhance subsequent development of T-cell-mediated immunity.

Examples of relevant topics include:

• Mechanistic studies of Mtb or Mtb/HIV infection events before the TB granuloma is developed in the alveolar/pulmonary tissue setting focused on identification of immunomodulatory therapeutics such as vaccine adjuvants.
• Host-pathogen interaction studies within the airways or lung to define early-stage Mtb-mechanisms of immune disruption with or without HIV co-infection.
• Studies of early Mtb infection during any stage of HIV infection (including virally suppressed on antiretroviral therapy).
• Impact of HIV infection on the biology of alveolar macrophages and other innate cells during early Mtb infection as well as the impairment of adaptive immunity.
• How the interactions among innate and adaptive immune cells during early Mtb infection affect the ultimate outcome of the host immune response in people living with and without HIV.
• Basic immunologic research to describe the early immune response after Mtb challenge with or without HIV.

Conversely, NIAID will consider applications in the following areas to be nonresponsive and not review them:

• Studies not focused on mechanisms of early infection with Mtb (defined as the time between Mtb exposure and early-stage granuloma development).
• Studies primarily focused on latency, chronic disease, or reactivation of established Mtb infection.
• Studies of a single cell type in early Mtb infection unless the studies are within a broader context and include a focus on interactions with other host cells (immune and/or non-immune) within the airway and lung.
• Applications with identified interventions primarily focused on testing the effectiveness of the intervention and not mechanistic aspects of the intervention.
• Clinical trials.
• Studies focusing on model development.

Award Information

Application budgets are not limited but need to reflect the actual needs of the proposed project.

The maximum project period is 5 years.

Applications are due on October 11, 2023, by 5 p.m. local time of the applicant organization.

Direct inquiries to Dr. Robert Mahon, NIAID’s scientific/research contact, at Robert.mahon@nih.gov or 240-669-5427. For your peer-review related inquiries, contact Dr. Robert Unfer at Robert.unfer@nih.gov or 240-669-5035.

NIAID’s new notice of funding opportunity (NOFO) Pulmonary Outcomes and Sequelae after Treatment-TB (POST-TB) (R01, Clinical Trial Optional) invites epidemiological and observational research projects on the long-term cardiopulmonary sequelae following treatment for tuberculosis (TB) in persons living with and without HIV infection. A better understanding of post-TB lung disease (PLTD) should yield better targets for interventions to reduce the burden of long-term cardiopulmonary disease sequelae following treatment for TB.

For this NOFO, investigators should evaluate the epidemiology and clinical manifestation of post-TB lung dysfunction, risk factors for dysfunction, predictors of severity, correlates of immune system responses (cellular as well as humoral), biomarkers of lung damage, and the impact of HIV infection and its treatment on PTLD. We also encourage investigators to explore mechanisms of pathology and the risk of recurrent TB or other disease.

We expect researchers will include participants during, after, or long after TB treatment. Studies could add clinical and immunologic evaluations during treatment, and at treatment completion, as well as include persons long after a well-documented TB treatment episode where data and samples enable in-depth research.

You might also employ case-control study designs to compare persons with a history of TB to suitable controls. It should be noted that the emphasis is on understanding PTLD in persons with and without HIV who have uncomplicated TB disease and who are cured by therapy. Enrolled participants should meet or be likely to meet the current WHO definitions for treatment cure or completion and not have been considered "lost to follow-up" at any time during their treatment.

The NOFO provides a nonexclusive list of example research topics:

• In-depth assessments of lung dysfunction prevalence and severity in persons cured of TB infection.
• Measures of immune system responses (cellular as well as humoral) and their impact on lung function over time.
• The impact of HIV infection on the severity or type of dysfunction after TB cure.
• Predictors and correlates of dysfunction and severity of damage.
  • Identification of biomarkers predictive of PLTD occurrence and severity.
  • Individual vulnerabilities and resilience to PLTD occurrence and severity.
  • Structural vulnerabilities and resilience to PLTD occurrence and severity.
• Risk of recurrent TB and other lung or respiratory infections.
• Risk of cardiovascular disease or chronic organizing pneumonia and chronic obstructive pulmonary disease in persons with PLTD.
• Quantification of the burden of PLTD on patients and their families.

You could also evaluate the incidence of cardiopulmonary disease in HIV-infected and uninfected persons, immunologic factors and biomarkers indicative of lung damage, and the impact of other potential risk factors such as alcohol or tobacco use, nutritional status, and environmental exposures. Further, you may consider preventative care such as pneumococcal and influenza vaccination, including antibiotic use in respiratory infections.

Conversely, NIAID will deem nonresponsive and not review applications that propose:

• Studies focused only on the pharmacologic or clinical impact of individual TB drugs, short-, or long-course treatment regimens.
• Studies of persons with multidrug-resistant or extensively drug-resistant TB, or those with poor adherence to TB therapy.

Clinical trials are optional but, for the sake of completing application forms properly, you need to be clear on whether or not your proposed research meets NIH’s Definition of a Clinical Trial.

Administrative Requirements

The NOFO does not set a budget cap, although your budget needs to reflect the actual needs of the proposed project. For a budget request with direct costs exceeding $500,000 in any 1 year, you must receive NIAID’s approval before submitting. The scope of the proposed project should determine your project period, although the project period cannot exceed 5 years.

Foreign organizations are eligible to apply. Foreign components are allowed.

The NOFO uses NIH’s standard due dates for AIDS and AIDS-Related Applications. The first submission deadline is September 7, 2023.

If you have any questions about the NOFO, direct them to NIAID’s scientific/research contact Dr. Robin Huebner at rhuebner@niaid.nih.gov or 240-627-3216

NIAID supports basic research on microbiology and immunology that may lead to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases.

NIAID’s Division of AIDS is seeking a partner to operate the Cellular Immunology Core Laboratory, which will conduct, analyze, develop, optimize, and validate cellular immunologic assays for HIV, Simian Immunodeficiency Virus, Mycobacterium tuberculosis, and other pathogens, to be performed on fresh and frozen preclinical samples.

A new request for proposals (RFP) seeks contractors who can do the following:

• Conduct validated immunological assays using good laboratory practice (GLP)-like processes
• Perform data analyses
• Receive, store, catalog, track, and maintain an inventory of the specimens for evaluation
• Manage, report, and deposit study data
• Perform project management activities related to contract activities
• Conduct initial and final transition activities, as needed

The contractor shall use current state-of-the-art technologies, including, at a minimum, ELISPOT, intracellular cytokine staining, flow cytometry, cell sorting, tetramer staining, and other assays to accomplish the technical objectives, and shall incorporate new and optimized technologies for assay development into contract activities when appropriate. Assays shall incorporate appropriate positive and negative controls using reference panels to define background and dynamic range and shall demonstrate reproducibility and consistency.

Additionally, the contractor shall also use state-of-the-art methods to analyze the data generated by the conduct of the assays, which may require different data analysis methods/platforms as appropriate for each type of assay. Data analyses may require generating publication quality figures, when directed by the contracting officer’s representative. Lastly, an independent Quality Assurance Program, not associated with the contract, shall conduct regular inspections to review facilities, equipment, personnel, methods, practices, and records.

Details and Due Date

Read the RFP Cellular Immunology Core Laboratory for complete details.

NIAID anticipates awarding one cost reimbursement, level-of-effort (term) type contract for a 1-year base period plus six 1-year options for a total possible performance period of 7 years, beginning on March 1, 2024.

Proposals are due on March 17, 2023, by 3 p.m. Eastern Time. Submit applications online through NIH’s electronic Contract Proposal Submission (eCPS) site.

Send inquiries to Kimberly Dormer, NIAID’s contract specialist for this opportunity, at kimberly.dormer@nih.gov.