Part 1. Overview Information

Key Dates

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.

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this notice of funding opportunity (NOFO) is to solicit applications from eligible organizations to participate in a cooperative research group, the Mucosal Immunology Studies Team (MIST). The objectives of MIST are to discover and define novel basic immune mechanisms, cells, mediators, and pathways that provide a more complete understanding of mucosal immune mechanisms; to explore innovative hypotheses; and to address difficult unsolved questions in mucosal immunity. The eventual goal is to gain insight into how the mucosal immune system responds to microbial factors at barrier surfaces, maintains homeostasis, and communicates systemically in health and disease. Studies may use relevant animal models or human tissues to achieve this goal. This program is not intended to support development and/or evaluation of mucosal vaccines or therapies, or research primarily focused on pathogens.

Background

The mucosal immune system satisfies a range of diverse requirements from maintaining a limited microbial burden in the lungs and upper reproductive tract to coexisting with many trillions of microbes in the large intestine. An imbalanced mucosal immune response to food, allergens, microbial flora, or pathogens can lead to tissue damage or chronic inflammation. Therefore, responses at the mucosa require tight regulatory control. Recent discoveries have established that the mucosal immune system connects to other body systems in addition to the systemic immune system. In particular, cross-talk between gut microbiota and the mucosal immune system has been shown to influence multiple aspects of human health and disease that, in addition to immune-mediated diseases, includes obesity, nervous system/mental health disorders, and hepatic and cardiovascular diseases. Still, much remains unknown in these areas.

With the goal of promoting a collaborative program to encourage basic and translational research focused on immunity at mucosal surfaces, the Mucosal Immunology Studies Team (MIST) was initiated in 2011 (RFA-AI-10-008), renewed in 2016 (RFA-AI-15-023) and again in 2021 (RFA-AI-20-027). The program has supported 28 U01 awards, two cores (imaging, animal models), and 56 pilot projects including early career awards, innovative collaborations, and translational projects.

Research Objectives and Scope

This NOFO will support research to define fundamental aspects of immunity at mucosal surfaces. This NOFO intends to stimulate new basic and applied research that will contribute toward understanding broadly applicable mechanisms of mucosal immunology.

Areas of interest and research studies responsive to this NOFO include, but are not limited to, those listed below. Many of the following areas of investigation are not new, but advances in recent years suggest that these areas have matured to a level where directed research efforts can have an impact. These and other research areas may be addressed in this NOFO in the context of defining new mechanisms relevant to immune responses at the mucosa. If infectious organisms, vaccines, adjuvants and/or mucosal diseases are used for the proposed studies, they must be employed as model agents and/or diseases to probe host mucosal immune responses to discover new information about mechanisms of immunity. Studies may use relevant animal models or human tissues to achieve this goal.

Mucosal Epithelium: Barrier, Defense, Antigen Sampling, Immune Response Orchestration. Mucosal surfaces are lined by tightly joined epithelial cells, which form a physical barrier between the body and the microbial flora, thereby serving as a first line of immune defense against microbial invasion. Mucosal epithelial cells secrete a wide array of substances such as mucins, anti-microbial peptides, surfactant proteins, lipids, lysozyme, and nitric oxide, which non-specifically shield the mucosa from microbial damage. Mucosal epithelial cells are capable of innate recognition of microbial motifs via cell surface or cytosolic molecules, such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) molecules, and retinoic acid-inducible gene (RIG-I) like molecules, which trigger the production of cytokines and chemokines that activate and mobilize immune cells. Specialized epithelium and epithelial cells (e.g., M cells, Paneth cells, goblet cells, tuft cells, follicle-associated epithelium) further contribute to immune responses by antigen/chemical recognition, transport of antigens across the mucosa, and presentation of antigens to dendritic cells (DC) or other immune cells within the mucosa. These mucosal epithelial cell types and their mediators serve to provide protection from pathogens, shape the microbiota, and influence host immune responses. How epithelial cells interact with and respond to luminal molecules and microbes is critical to orchestrating the balance of effector and regulatory responses needed to respond appropriately to pathogens. In addition, epithelial cells must maintain tolerance to innocuous antigens in air, food, and the microbial flora. The mechanisms, cells, and pathways governing epithelial barrier integrity, antigen recognition and acquisition, and presentation to DCs and immune cells to induce protection, ignorance or tolerance are important areas for further study.

Examples of potential research studies in this area include, but are not limited to:

• Signals that drive antigen-sampling epithelial cells at respiratory and other mucosal sites to become M cells
• Molecular pathways involved in apical-to-basolateral translocation of luminal antigens
• Regulation of goblet cell sentinel and antigen capture functions at diverse mucosal sites
• Mechanism of sensing pathogens or allergens by chemosensory tuft cells in the airway
• Relative contribution of specialized mucosal epithelial cells to mucosal surveillance, immunity, and tolerance
• Epithelial factors influencing dendritic cell or T cell recruitment and differentiation
• Functional consequences of MHC Class II expression on epithelial cells of the lung and intestine
• Tissue-specific sites of presentation of antigens taken up in the lung, intestine, or urogenital tract; and influence of local conditions on resultant responses
• Role of mucus in attenuating microbial virulence and in shaping immune responses

Mucosal Immunoglobulin and Mucosal B Cell Responses. IgA isotype antibodies predominate at the mucosal surface and are considered a first line of defense against microbial invasion through the mucosa. Particularly important functions of these antibodies are protection against infections and establishment of a healthy microbiota. Despite discoveries that have provided a framework for understanding induction of IgA-producing B cells and transport of IgA, much remains unknown, for example, where and how B cells meet antigen, what factors influence the site of IgA production in the gut, where long-term memory is established, and how responses to infection and commensal microbes differ at various mucosal sites. To facilitate mucosal vaccine development, more information is needed to 1) understand where and how local IgA is produced and 2) identify the precise role of IgA and other mucosal immunoglobulins in protecting against infectious pathogens and maintaining a balance with commensal microbes.

Examples of research studies in this area include, but are not limited to:

• Strategies to induce IgA at stratified epithelial mucosa, such as the lower female reproductive tract
• Contribution of Peyer’s Patch CD4 T cell subsets to IgA B cell differentiation
• Origin of T follicular helper T cells (Tfh) at mucosal locations
• Role of FoxP3+ regulatory T cells (Tregs) and follicular regulator cells (Tfr) in production of affinity-matured gut IgA antibodies
• Epithelial, stromal, and dendritic cell mechanisms involved in development of IgA-producing B cells

Mucosal Immunity and Inflammation. The mucosal immune system is challenged to respond to harmful organisms while regulating the resultant influx of immune cells to prevent tissue injury due to inflammation. In the gut, several lines of evidence support the idea that the commensal flora exert an anti-inflammatory influence on the mucosa. Alterations in microbial flora may lead to inappropriate responses in which commensal microbes serve as surrogate pathogens and thus stimulate a chronic inflammatory response. In the relatively less colonized surfaces of the respiratory tract, failure to tightly control immune responses to pathogens or commensal microbiota can also lead to chronic inflammation and tissue destruction. To limit inflammatory responses, the airways, gut, and other mucosal surfaces employ a range of complex physical, innate, and adaptive immune defenses. Alterations of any of these defenses could promote an uncontrolled inflammatory response that may lead to tissue injury, and also may promote pathology at distant non-mucosal sites, such as the central nervous system or the cardiovascular system. Complex mucosal systems to prevent responses to harmless antigens and limit inflammatory responses to pathogens are not well understood and represent an important area for further study.

Examples of research studies in this area include, but are not limited to:

• Mucosal immune mechanisms in pathogen and disease tolerance that limit tissue destruction or inflammation
• Influence of circadian rhythms on immune cell/pathway functions in homeostasis, protective immunity, and inflammation
• Mechanism and effects of immune scarring at the mucosa that lead to lasting mucosal changes evident long after or in the absence of pathogen infections (e.g., urothelial cell changes influencing recurrent bladder infection, recurrent enteric infections leading to an inflammatory bowel disease (IBD)-like syndrome, airway remodeling in airway disease)
• Mechanisms of lung-gut cross-talk that affect mucosal immunity and mucosal inflammation
• Role of trained innate immunity in mucosal infection and chronic inflammation
• Identification and mechanisms of action of dietary factors, microbes, and microbial metabolites that influence mucosal immunity and inflammation
• Role of innate lymphoid cells, Mucosal-associated invariant T (MAIT) cells, gamma delta T cells, resident T memory cells, and regulatory T cells in mucosal protection, inflammation, and tolerance
• Defining correlates of mucosal protection or tolerance and predictors of inflammatory outcome in humans
• Mechanisms by which mucosal responses differ between microbial infection of the upper vs. lower airways

Mucosal Immune System Cross-Talk with the Nervous System. Numerous connections among the microbiota, mucosal immune system, and nervous system have been identified, suggesting an interplay among the nervous and mucosal immune systems in detection and response to microbes and other molecules at mucosal surfaces. Tissues that are directly exposed to the external microbial flora such as mucosal surfaces of the digestive, lung, and urogenital tracts play a central role in immune surveillance. These sites are densely innervated by nervous system sensory cells, which recent pioneering studies have found to be important in regulating 1) mucosal immune cells, 2) their responses, and 3) barrier integrity. Effective communication between the mucosal immune and nervous systems shapes homeostasis of the GI and respiratory systems, can allow for more integrated detection and response to environmental insults and infectious agents, and may fine-tune responses to pathogens and tissue damage. Understanding how neuro-immune interactions shape responses to microbes, allergens, and other environmental stimuli is critical for identification of novel targets for development of future therapeutics for mucosal infections and inflammation, as well as disorders that may be initiated at mucosal surface, but manifest at non-mucosal sites such as the nervous system or cardiovascular system.

Examples of research studies in this area include, but are not limited to:

• Mechanisms by which the enteric and/or respiratory nervous systems and central nervous system integrate with microbe-induced mucosal immune responses
• Role of the nervous system in immune system development at mucosal sites
• Mechanisms of cross-talk between mucosal neurons and glial cells and mucosal immune cells, e.g., mast cells, macrophages, innate lymphoid cells (ILCs), lymphocytes, and mucosal epithelial cells
• Effects of the microbiota on the peripheral enteric nervous system and how this influences development of the mucosal immune system
• Immune consequences of ILC interactions with neurons at mucosal sites
• Nervous system involvement in restraining versus promoting immune responses

Mucosal Immunity in Systemic Health and Disease. Emerging paradigms suggest that mucosal immunity has wide-ranging impacts in human health and disease. As such, maintaining homeostasis at mucosal barrier surfaces is central to overall organismal health. These processes involve interactions between immune cells and diverse cell types and organ systems that are not traditionally associated with mucosal immunity. In addition, immune responses that are primed and conditioned at mucosal barrier sites have inter-organ effects, subsequently impacting disease pathophysiology at tissue sites distal to the mucosa. Focus on these new emerging areas of mucosal immunology may push this field forward in the development of next generation mucosal immune-focused vaccines and immunotherapies.

Examples for research studies in the area include, but are not limited to:

• Interactions between the mucosal immune system and less studied cell types at mucosal barriers associated with the nervous system, stroma, endothelium, and endocrine system
• Interrogation of immune responses initiated and conditioned at mucosal barriers, including the intestine or airway, the inter-organ system consequences, and impact on pathophysiology of distal immune-mediated diseases such as psoriasis, arthritis, multiple sclerosis, neurodegeneration, and hepatitis
• Cross-disciplinary interactions between the mucosal immune system and organ systems including the gut, lung, liver, central nervous system, joints, skin, and kidneys
• Mucosal immunity shaping of the efficacy or adverse outcomes of specific therapies
• Modeling mucosal immune interactions with diverse cell types or inter-organ systems in human samples or in vitro systems

The MIST program is intended to support studies that break new ground in the understanding of mucosal defense and mucosal immunoregulation. Proposed studies may include a range of mucosal probes to gain new insights into mucosal immune defense mechanisms, such as microbes, pathogens, vaccines, adjuvants, infections, and mucosal inflammation.

Applications that propose to conduct research in the following areas will be considered non-responsive and will not be reviewed:

• Clinical trials; however, the use of samples obtained from human subjects in clinical trials funded through other mechanisms is allowed.
• Studies involving HIV, AIDS, SIV.
• Studies focused solely on skin or epidermis without a connection to mucosal immune function.
• Studies focused primarily on specific microbes, infections, vaccines, or adjuvants that do not use these agents as probes to gain new insights about mucosal immune mechanisms.
• Studies focused on non-immune mechanisms of pathogenesis, such as non-immune factors involved in impaired tight junction integrity and increased intestinal permeability; genetics linked to non-immune related epithelial barrier dysfunction.
• Projects focused on autoimmune or inflammatory diseases (e.g., inflammatory bowel disease, celiac disease, cystic fibrosis, etc.), lung or intestinal transplantation, or asthma/allergy that do not use these diseases as probes to gain new insights about mucosal immune mechanisms.
• Investigations that do not focus on the study of mucosal immune or immunoregulatory mechanisms, mucosal cells, mucosal molecules or mucosal pathways.

Steering Committee. A Steering Committee will be established to direct the overall efforts of the MIST program. The Steering Committee will be composed at a minimum of the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of each of the awards and an NIH Project Scientist. The Steering Committee will develop a "MIST Plan" that will articulate the goals of the MIST Program and will be used as a reference for making recommendations regarding use of the Infrastructure and Opportunities Fund (IOF). The Steering Committee will be responsible for organizing an annual competition for high priority research projects aligned with the MIST research goals that could be funded through the IOF. The oversight of these activities will facilitate and enhance cooperative and collaborative efforts, among both MIST members and the research community at large, that are best suited to achieve the goals of the program and to advance understanding of immune mechanisms at the mucosa.

Infrastructure and Opportunities Fund (IOF). To capitalize on emerging opportunities and sharing of resources and expertise consistent with the goals of MIST, an IOF will be made available. Examples of activities supported by the current IOF include development and management of a website for MIST activities; collaborative and pilot and/or feasibility projects among MIST members; translational projects; early-stage investigator projects; and imaging and animal model development cores. IOF projects must be within the scope of this NOFO and may be submitted by all MIST members.

IOF Management. One institution will be chosen by NIH after award from the successful applicants to manage the IOF for the entire MIST. This institution must agree to take responsibility for managing the IOF, including establishing an administrative structure for disbursement and tracking funds, and under the advice of the Steering Committee, establishing procedures for reporting status of IOF projects to NIH and the Steering Committee.

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

Section II. Award Information

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

Higher Education Institutions - Includes all types

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

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
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign Organizations/ International Collaborations

NIH will no longer issue awards (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. This new requirement was effective, May 1, 2025.

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.

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

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 the 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.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an 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.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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.

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 Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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. Conformance to the requirements in the 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.

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

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

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

Other Attachments: The following attachment is required for this NOFO and must be included as a separate pdf attachment. If absent, the application will be considered incomplete and will not be reviewed.

Infrastructure and Opportunities Fund (IOF) Management Plan: The filename “IOF.pdf” should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Applicants must include a plan (maximum of 3 pages) for administering the IOF to include coordination, communication, and management of the proposed IOF; proposed measures and procedures for disbursement, reporting and monitoring of expenditures; and plans for soliciting, evaluating, and selecting projects. Applicants should NOT include or propose specific projects to be funded from the IOF; these decisions will be made in conjunction with the Steering Committee after award.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

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

In the budget section, applicants should include funds for travel to the Rockville, Maryland area for two Steering Committee meetings within the first 12 months, and usually once annually thereafter, for the PD(s)/PI(s). For multi-PD/PI applications, the budget should include travel funds sufficient for all PD(s)/PI(s) to attend the Steering Committee meetings.

All applicants must propose an IOF Budget. One (1) IOF budget of up to $750,000 total costs will be awarded to one recipient organization, which will be selected by NIAID post-award to manage the fund. Each applicant should propose Direct Costs as a single line item in the Other Direct Costs Category of the Budget. Direct Costs proposed for the overall administration and oversight of the IOF may be requested and must comply with NIH Grants Policy. Direct Costs for the research projects using IOF funds should be estimated at 4-8 pilot projects per year. F&A costs will be applied in accordance with NIH Grants Policy.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

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

Specific Aims: List the broad, long-range objectives and goals of the proposed project and describe the work to be completed. 

Research Strategy: Within the research strategy, applicants must include the following:

A clear and detailed description of how the proposed studies contribute knowledge critical to achieving the goal of advancing understanding of mucosal immune mechanisms or addressing difficult unsolved questions in mucosal immunity.

A clear and detailed description of how the proposed studies explore hypotheses related to immunity at mucosal surfaces and/or identify or define basic mucosal immune mechanisms, cells, mediators, and pathways.

If approaches including infectious organisms, vaccines, adjuvants and/or mucosal diseases are proposed, describe how these model agents and/or diseases will advance research towards discovery of new information about basic mechanisms of mucosal immunity (e.g., cells, mediators, pathways) beyond the current level of understanding.

Describe in detail the rationale behind the choice of any proposed animal models or human tissues and how their use will advance the research strategy.

Letters of Support: Infrastructure and Opportunities Fund Management - All applicants should include a letter from the PD(s)/PI(s) and the Institution's Signing Official agreeing to take fiscal responsibility for the management of the IOF, if chosen by NIAID to do so.  

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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

All instructions in the How to Apply- Application Guide must be followed.

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.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute of Allergy and Infectious Diseases, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining and coordinating the scientific and administrative activities of the approved projects.
• Acceptance and implementation of common guidelines approved by the Mucosal Immunology Studies Team (MIST) Steering Committee.
• Attendance at the annual Steering Committee meetings.
• Timely publication of major findings; submission of manuscripts to the NIAID Program Officer promptly upon acceptance for publication.
  • Publication of results from collaborative projects supported by the Infrastructure and Opportunities Fund (IOF) must abide by the guidelines established by the Steering Committee with NIH assistance.
  • Publication of findings linked to clinical trials (for example, mechanistic studies that utilize samples from a clinical trial) must adhere to the policies enacted by the governing body of the clinical trial and the sponsor of the trial.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIAID Project Scientist will support MIST activities through scientific interactions with the Program Directors/Principal Investigators [PD(s)/PI(s)] and collaborators and may provide appropriate assistance, including: 1) advising on the selection of resources, 2) providing advice and guidance on technical issues, performance, the collection and/or analysis of data, and 3) participating in the preparation of publications for collaborative projects, as appropriate.
• The NIAID Project Scientist may advise in the design of the research activities and work closely with award recipients and other member scientists to facilitate collaborations and coordination of project activities. 
• NIH may appoint up to two external scientists or two additional NIH staff to the Steering Committee as non-voting members.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Steering Committee

• A Steering Committee will serve as the governing body of MIST. All MIST investigators and recipients of IOF funding will be required to accept and implement common guidelines and procedures approved by the Steering Committee.
• Develop a "MIST Plan" to articulate the goals of the MIST Program leading to recommendations regarding use of the Infrastructure and Opportunities Fund (IOF). The Steering Committee will be responsible for organizing an annual competition for high priority research projects aligned with the MIST research goals that could be funded through the IOF. 
• One PD/PI from each award will act as a voting member of the Steering Committee.
• The NIAID Project Scientist, although a member of the Steering Committee, will not have voting rights or responsibilities.
• It is anticipated that Steering Committee decisions will be reached by a consensus vote.
• The Steering Committee may appoint additional non-voting members by majority vote.
• A chairperson will be selected from among the non-Federal Steering Committee members.
• The details and responsibilities of the Steering Committee will be negotiated at the time of award or post-award.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Margaret Morris Fears, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Svetlana Alperovich
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6895
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.