RFA-AI-28-005-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title

Immune Tolerance Network (UM1 Clinical Trial Required)

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

Reissue of

RFA-AI-19-068

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-AI-28-005

Companion Funding Opportunity

None

Number of Applications

Only one application per institution is allowed, as defined in Part 2, Section III.3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.855

Funding Opportunity Purpose

The purpose of this notice of funding opportunity (NOFO) is to support applications to continue the Immune Tolerance Network (ITN). The primary objective of the Network is to develop tolerogenic therapies for immune-mediated disorders. The three main clinical areas of work are: 1) Allergic diseases and asthma; 2) Autoimmune diseases; and 3) Immune-mediated consequences of transplantation. The core functions of the ITN include designing, conducting, and sharing the results of clinical trials and performing integrated mechanistic studies.

Funding Opportunity Goal(s)

To assist public and private nonprofit institutions and individuals to establish, expand and improve biomedical research and research training in infectious diseases and related areas; to conduct developmental research, to produce and test research materials. To assist public, private and commercial institutions to conduct developmental research, to produce and test research materials, to provide research services as required by the agency for programs in infectious diseases, and controlling disease caused by infectious or parasitic agents, allergic and immunologic diseases and related areas. Projects range from studies of microbial physiology and antigenic structure to collaborative trials of experimental drugs and vaccines, mechanisms of resistance to antibiotics as well as research dealing with epidemiological observations in hospitalized patients or community populations and progress in allergic and immunologic diseases. Because of this dual focus, the program encompasses both basic research and clinical research.

Key Dates

Posted Date

October 20, 2026

Open Date (Earliest Submission Date)

December 29, 2026

January 29, 2027

January 29, 2027

Not Applicable

February 2028

All applications are due by 5:00 PM local time of applicant organization.

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.

Expiration Date

January 30, 2027

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background and Research Scope Inducing immune tolerance is a primary goal for preventing and treating immune-mediated diseases. Immune tolerance strategies aim to block harmful immune responses while leaving protective immunity intact. Decades of basic immunology research provide a strong foundation for applying such strategies to current and future clinical challenges. The Immune Tolerance Network (ITN) has conducted clinical and mechanistic studies of immune tolerance in the fields of allergy and asthma, autoimmunity, microbiome and immune system interactions, chronic inflammation, and prevention of transplant rejection.

This notice of funding opportunity (NOFO) will support a cross-disciplinary consortium responsible for conducting research in three areas of immune-mediated conditions. Input from clinicians and immunologists, both within and outside the Network, will be important toward the design, development, and conduct of clinical trials and integrated mechanistic studies. The three clinical areas, along with examples of high-priority research topics, include:

Allergic Diseases and Asthma Allergic diseases and asthma are the most common chronic conditions of children in the United States and are among the leading chronic conditions of adults. Immune tolerance research in this field seeks to prevent or reverse pathogenic immune responses to the allergens that relate to these conditions. Within this clinical area, priority areas of research the ITN will support include:

Autoimmune Diseases Approximately 50 million Americans are living with autoimmune diseases, making them among the most common chronic conditions in the United States. New approaches are critically needed to prevent disease and/or restore normal immune function. Within this clinical area, priority areas of research the ITN will support include:

Transplantation Organ transplantation saves tens of thousands of lives annually, yet long-term success is challenging, with 10-year graft survival rates ranging from <30% for lung to 60-70% for kidney transplant recipients. Although >49,000 organ transplants were performed in the United States in 2025, there were >81,000 waitlist additions, with >100,000 candidates remaining on waitlists at the end of 2025. Immune tolerance research in transplantation aims to prevent graft rejection and reduce long-term health impacts of immunosuppressive drugs and reduce the need for repeat organ transplantation. Within this clinical area, priority areas of research the ITN aims to support include:

Functional Areas The ITN is structured to satisfy the following four functions: Leadership, Clinical Operations, Core Laboratory (or laboratories), and Bioinformatics. These functions are integrally connected to all aspects of the clinical areas of interest. The Network functions as a collaborative unit under the direction of the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)). The functional areas and their overall roles and responsibilities include:

Leadership: The PD(s)/PI(s) will serve as the overall administrative leadership and financial governance of the Network. Leadership is responsible for establishing the Network's research priorities, governance, and quality management, including oversight and evaluation of all Network activities. Leadership is also responsible for the following:

Clinical Operations:

Core Laboratory:

Bioinformatics:

Resources In support of the ITN, NIAID serves as the regulatory sponsor for most Network clinical trials conducted under Investigational New Drug (IND) Applications, Investigational Device Exemptions (IDEs), and international equivalents, assuming full sponsor regulatory responsibility and will be responsible for several resources to support clinical trial design, implementation, oversight, and data analysis, to include but not limited to:

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Applications Not Responsive to this NOFO The following types of applications are not responsive to this NOFO and will not be reviewed:

Applications that do not cover all three clinical areas

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Renewal

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIAID intends to commit $27M in FY 2028 to fund one award.

Award Budget

Application budgets are not expected to exceed $23M per year in direct costs and should reflect the actual needs of the proposed project.

Award Project Period

The project period must be 7 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

Independent School Districts

Public Housing Authorities/Indian Housing Authorities

Native American Tribal Organizations (other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

Regional Organizations

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

Only one application per institution (normally identified by having a unique UEI or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following additional instructions:

Within the Research Strategy, including the following subsections with the indicated page limits:

Subsection A: Overview of the Immune Tolerance Network – one required - 12 pages Subsection B: Leadership – one required - 30 pages Subsection C: Clinical Operations – one required - 30 pages Subsection D: Core Laboratory – one required - 30 pages Subsection E: Bioinformatics – one required - 12 pages

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

SF424(R&R) Other Project Information All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Facilities and Other Resources Describe the unique and essential components of the facilities and resources that will be required for:

SF424(R&R) Senior/Key Person Profile

R&R Budget All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Applicants must request all necessary funds to support the infrastructure and operations of the entire Network. For budgeting purposes, applicants should plan according to the information provided below:

Outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Provide the specific aims for the Network and describe how they support the proposed Network research agenda.

Research Strategy: The Research Strategy section should consist of a single attachment consisting of subsections A-E, as designated below.

Subsection A. Overview of the Immune Tolerance Network Describe the overall Network structure and function with respect to advancing immune tolerance induction strategies through clinical trials and integration of studies of underlying mechanisms of the induction, maintenance and loss of tolerance. From a high-level perspective, describe approaches for integration of the four Network functional areas (Leadership, Clinical Operations, Core Laboratory, and Bioinformatics) and coordination with clinical sites to create a fully integrated, collaborative organization. Provide organizational charts, diagrams or other tools to represent the Network. Discuss how the proposed organization will facilitate decision-making and the ability to complete studies.

Subsection B: Leadership Describe the functions of leadership and discuss how the organizational structure promotes effective leadership of the overall Network and proposed activities. Provide tables, diagrams, flow charts or organizational charts to reflect the organization of the Network's four functional areas and activities, e.g., Network Executive Committee, Network Steering Committee, or subcommittees proposed. Include the following information:

Network Structure and Governance:

Describe the following:

Network Operations:

Describe and/or provide the following:

Network Evaluation and Improvement:

Describe the following:

Network Research Agenda:

Describe and/or provide the following:

Subsection C: Clinical Operations Describe the following:

Study Feasibility Assessment:

Describe the following:

Protocol Development:

Protocol Implementation and Oversight:

Describe the following:

Subsection D: Core Laboratory (or laboratories)

Clinical Site Laboratory Capacity and Training:

Subsection E: Bioinformatics Structure and Governance:

Describe the following:

Data Services System:

Describe the following:

Primary and Secondary Analyses:

Describe the following:

Letters of Support:

The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).

Provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators.

To document their commitment, include letters in support of the following:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

Delayed Onset Study Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

All applicants must add and complete the Delayed Onset Study record and must check box "Anticipated Clinical Trial?"

Study Title-- use: "Multiple Delayed-Onset Studies" Justification Attachment: Indicate each clinical study protocol developed during the project period will be subject to approval through a procedure that involves an initial concept submission and subsequent review by the Immune Tolerance Network. If the concept receives approval, the next stage will be development of the protocol, which also must undergo review and approval prior to implementation through the Immune Tolerance Network.

PHS Assignment Request Form

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372) This initiative is not subject to intergovernmental review.

6. Funding Restrictions All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and…