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 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



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

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications to participate in the Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) Region Genomics in Immune-Mediated Diseases Consortium (HLA and KIR RGC). The goals of the HLA and KIR RGC are to 1) define associations between variations in HLA and KIR genetic regions and immune-mediated diseases; 2) elucidate mechanisms underlying these associations with the goal of advancing therapeutic opportunities; and 3) validate association data in order to improve predictive power of clinical disease screening.

To support these goals, this Consortium will continue to develop and utilize cutting-edge technologies and analysis pipelines to generate high quality HLA and KIR sequences and disease association data that will be submitted to the Immunology Database and Analysis Portal (ImmPort) and, when appropriate, a publicly accessible database such as the Database of Genotypes and Phenotypes (dbGaP) or the Immuno Polymorphism Database (IPD).

Background

Located on the short arm of chromosome 6,the human major histocompatibility complex (MHC) region, also known as the HLA region, is the most polymorphic and gene-dense region of the entire human genome and is critical to both innate and adaptive immunity. While the classical HLA region contains 224 gene loci and spans 3.6 megabases (Mb), the extended HLA region contains 421 loci over 7.6 Mb and includes additional immune-relevant genes as well as genes in high linkage disequilibrium with the classical region. In the extended region, 252 genes are classified as protein-coding genes, which include the HLA Class I, II, and III gene families. The Class I and Class II genes encode molecules responsible for the presentation of endogenously and exogenously derived peptides to T cells. The Class III region contains genes encoding a variety of immune response mediators, including complement components and cytokines. HLA polymorphism enables effective immune responses against a wide variety of pathogens, but that variation is problematic in the setting of transplantation where HLA mismatching between a donor and recipient is associated with worse outcomes compared to optimally matched donor-recipient pairs. Additionally, hundreds of diseases, including most autoimmune diseases, have described associations with certain classical HLA class I and II alleles. Nonetheless, identification of the primary etiology of disease is complicated by the use of low-resolution HLA typing, high linkage disequilibrium, and environmental factors that influence disease manifestation.

In addition to their role in peptide presentation, HLA Class I molecules act as ligands for KIR on natural killer (NK) cells. The interaction between HLA and KIR results in either inhibition or, less commonly, activation of NK cell cytotoxic activity. KIRs are encoded by a similarly polymorphic region located on chromosome 19 and have evolved to enable swift immune responses to a variety of threats. Specific combinations of KIR and HLA haplotypes have been linked to immune-mediated diseases and transplantation outcomes, suggesting that the study of these molecules in tandem may be especially valuable. Recently, KIR+CD8+ human T cells were found to have regulatory activity, resembling murine Ly49+CD8+ T cells and playing a role in maintaining peripheral tolerance.

HLA and KIR regions contain high degrees of polymorphism between individuals, and among racial and ethnic groups. To date, the IPD has curated and officially named over 35,000 HLA and 1,600 KIR alleles.This high degree of variation exists within areas of gene duplication encoding functional alleles as well as pseudogenes, resulting in unique sequencing challenges. Genome-wide association studies (GWAS) of immune-mediated diseases consistently show the highest level of association within HLA and KIR regions. However, conventional GWAS techniques based on single nucleotide polymorphism (SNP) arrays must rely on statistical imputation methods and availability of multi-ancestry reference panels to ascribe associations to these dense and polymorphic gene clusters. Increasing use of next generation sequencing (NGS) technologies and novel analytic approaches have enabled fine mapping of MHC and KIR region sequences and more reliable sequence imputation. These and similar advances allow for unambiguous identification of the polymorphisms implicated in disease risk or protection and facilitate mechanistic evaluations underlying disease associations.

Previous recipients (awards made under RFA-AI-19-041, RFA-AI-14-012, RFA-AI-14-013, and RFA-AI-09-030) characterized HLA and KIR regions in defined cohorts and provided significant insights into polymorphisms associated with autoimmunity, graft-versus-host-disease (GVHD) following hematopoietic stem cell transplantation, and other immune-mediated diseases including asthma, paraneoplastic syndromes, and primary immune deficiencies. High-resolution HLA and KIR sequences generated by these projects are submitted to ImmPort and publicly accessible databases, providing critical contributions to support a growing data infrastructure and future studies. The Consortium has facilitated the exchange of reagents and technologies, fostered collaborations across disease areas and disciplines, and revealed how common sequence variations within these regions may be linked to multiple diseases. More recent areas of interest have extended to investigation of mechanisms underlying associations and clinical application of findings through the development of risk assessment tools.

To most efficiently utilize research resources and rapidly exchange scientific information to promote HLA and KIR genomics research and NIH objectives, it is anticipated that cooperation or opportunities to collaborate with other NIH funded programs will be initiated in future years and will be coordinated and facilitated by the NIAID Project Scientist.

Research Objectives and Scope

The objectives of the HLA and KIR RGC program are to 1) define associations between variations in HLA and KIR genomic regions and immune-mediated diseases; 2) uncover mechanisms underlying these associations with the goal of advancing therapeutic opportunities, and 3) validate association data in order to improve predictive power of clinical disease screening. 

This initiative will support prospective and/or retrospective studies that investigate the relationship between genetic variation in HLA and KIR genomic regions and immune-mediated diseases, including susceptibility to or protection from disease onset, progression, and/or severity. Studies must focus on identifying novel associations with high resolution and/or validating previously described associations. All studies must also include associated clinical phenotype data. Cohorts should have broad racial and ethnic representation although less diverse cohorts may be used if justified based on known disease demographics. Accompanying mechanistic studies to determine association causality and development of analytic tools to facilitate clinical translation of findings are also supported under this initiative. Research projects that prioritize cohort diversity, mechanistic explorations, and/or enhanced interactions with clinicians in order to facilitate clinical validation and translation of findings to improve disease diagnosis and/or treatment are highly encouraged. Studies may examine polymorphisms in the protein coding and/or non-coding regions within the HLA and KIR regions, non-classical genes residing in these regions, as well as multi-allele associations.

Areas of focus may include:

• Acute or chronic transplant rejection, including the influence of donor/recipient matching on outcomes following solid organ or pancreatic islet transplantation (e.g., studies that explore the mechanisms underlying the observed association of outcomes with eplet matching scores (HLA-mM)
• Graft-versus-host disease following bone marrow transplantation
• Autoimmune diseases mediated by HLA and KIR genomic regions
• Neuro-immune and neuropsychiatric diseases and syndromes
• Allergy, including asthma and responses to environmental or food allergens
• Vaccines, drug sensitivities, or infectious disease, if studied in the context of their influence on development of an immune-mediated disease (e.g., Lyme arthritis, post-viral fatigue syndrome, post-COVID conditions,  post-vaccine Guillain-Barre syndrome)
• Immune-mediated diseases, including outcomes of organ transplantation, disproportionately prevalent or severe in specific racial, ethnic, or gender groups, especially minority populations
• Development or refinement of sequencing technologies and analytical tools to improve the identification, validation, and/or prediction of relative disease risk
• Studies of HLA-KIR region gene combinations
• Mechanistic studies that explore the molecular consequences of specific polymorphisms within HLA and KIR genomic regions on disease phenotype

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Type 1 diabetes association studies
• Infectious disease and vaccine response association studies that are not performed in the context of subsequent  development of immune-mediated disease
• Cancer association studies
• Animal studies, unless designed to support mechanistic evaluation of defined human disease associations
• Population diversity studies, unless performed in relation to immune-mediated disease prevalence or severity
• Clinical trials
• Serology-based HLA or KIR typing projects
• HIV/AIDS association studies
• Projects focused on drug development
• Mechanistic projects focused on animal models
• Projects that do not include a focus on identifying novel associations with high resolution and/or validating previously described associations and the associated clinical phenotype data.

Applicants are strongly encouraged to contact the Scientific Research Contacts well in advance of the application submission deadline to discuss the proposed research program.

Milestones

The research plan must include a realistic timeline for completion of study aims and explicit and quantitative annual milestones. These milestones will be used by NIAID program staff to assess annual progress and support funding decisions.

Steering Committee

All PDs/PIs of funded awards will serve on the HLA and KIR RGC Steering Committee (SC) whose purpose is to coordinate and facilitate activities of the Consortium, leverage existing research infrastructure and promote collaboration and sharing of samples, protocols, and experimental results. Steering Committee voting members will include the contact PD/PI from each U01 award. Voting members will elect a Chair by majority vote from among non-government Steering Committee members.   The steering committee will serve as the main governing board for this consortium. 

The Steering Committee will:

• Identify scientific opportunities, emerging needs, and impediments
• Identify opportunities for and encourage collaborations among Consortium members
• Provide guidance and recommendations to investigators regarding study implementation and conduct
• Establish policies for joint publication, data handling and interaction with ImmPort and NCBI staff, including protocols and standards for data collection, analysis, and management
• Ensure the timely release of data through publication and/or release of data to public databases
• Develop guidelines and policies for publication of collaborative project results
• Generate educational material including webinars, review articles, SOP for sequencing and bioinformatics analysis to improve program outreach and impact
• Organize a workshop during the first two years of the funding cycle focused on defining clinical relevance of known HLA and KIR disease association to facilitate collaborations and advance clinical translation of Consortium findings.
• Review each project’s progress in achieving set milestones and interim objectives, if requested by the NIH Program Officer(s)
• Prepare reports on cumulative progress of the cooperative group, as requested by the NIH Program Officer(s)
• Establish definitions and data collection standards that will allow pooling of data across studies and disease areas, as needed
• Establish subcommittees as needed to provide recommendations on shared aspects of the cooperative research group, including but not limited to the activities listed above.

NIAID Bioinformatics Information Support (ImmPort)

The ImmPort program will provide technical assistance and data submission support for HLA and KIR RGC recipients. The portal provides online tools that allows users to analyze data and visualize results, integrate data from a variety of laboratories, and supports collaboration among scientists. All the relevant data generated by the HLA and KIR RGC will be submitted to the ImmPort database. ImmPort will be responsible for data receipt, deposition, archiving and backup, and subsequent data deposition into dbGAP or other appropriate public databases. ImmPort will communicate with the data liaison for each U01 project.   

Plan for Enhancing Diverse Perspectives (PEDP) This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in  NOT-MH-21-310 , submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material .  The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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

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

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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) 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. 

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.
  • 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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

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 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Maryam Rohani, D.D.S., Ph.D.
Telephone: 301-761-6656 
Email: maryam.rohani@nih.gov 

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:

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers, and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.

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:

PEDP implementation costs: 

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm). 

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 Specific Aims of the proposed project. Concisely describe the hypothesis or hypotheses to be tested. In addition, state the project’s relationship to the goals of the HLA and KIR RGC.

Research Strategy: Provide a description of how the proposed research will contribute to meeting the HLA and KIR RGC's goals and objectives. Without duplicating information in the PHS Human Subjects and Clinical Trials Information, discuss the rationale for choosing the study cohorts and, as appropriate, disease impact on specific racial and ethnic groups, if known. Explain the rationale for selecting the methods to accomplish the Specific Aims and address how the project will advance understanding of the role of HLA and/or KIR region genes in immune-mediated diseases, and/or transplantation. In addition, state the biological significance of the research. Applicants are required to provide preliminary data. For association or validation studies, describe how phenotypic data will be captured, validated, and linked to later analyses. Document the availability of and timeframe for obtaining genetic material and phenotypic data necessary for the proposed project. Discuss how the proposed approach will facilitate clinical translation of findings to improve risk prediction and/or treatment outcome. Without duplicating information contained within the biosketch(es), discuss the composition of the research team in terms of expertise required to successfully 1) conduct the clinical and immunogenetic aspects of disease research directly relevant to the proposed project, 2) provide the required biostatistical support, and 3) act as an effective data liaison with ImmPort.

Milestones: Briefly describe interim and long-term objectives and annual milestones to be achieved during the project, identifying critical decision points and providing a detailed timeline for the completion of each goal of the proposed research project.

Data and Statistical Plan: Provide a detailed description of the statistical considerations used in determining sample size and study power, with a justification for the required sample size; details of data collection; and the capture and validation of demographic and phenotypic information. Provide a description of how interactions with ImmPort will be conducted.

Letters of Support: If the proposed study includes samples and clinical data that are not currently in the possession of the PD/PI, the application should include a letter of support from the person or institution controlling the samples indicating that the samples and associated clinical/phenotypic data will be made available to the applicant. 

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): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.
• All investigators funded under this NOFO will be expected to share their data publicly through ImmPort or other public portals approved by NIH. Therefore, the Data Management and Sharing Plan should include a summary of how the applicant will manage data submission and interactions with ImmPort.

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.

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 Information

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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

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 review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

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 National Institute of Allergy and Infectious Diseases, 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 on the basis of established PHS referral guidelines 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.

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

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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding. 

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. 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 addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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.

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:

• Accomplishing negotiated milestones.
• Collecting and assuring data quality; facilitating interactions with ImmPort staff through the data liaison; submitting data to ImmPort, and subsequent submission of these data to dbGaP by ImmPort in accordance with policies established by NIAID and NCBI and the NIH data sharing policy available at: https://grants.nih.gov/grants/policy/data_sharing/.
• Serving as voting members of the Steering Committee (one PD/PI if multiple PDs/PIs); and participating in HLA and KIR RGC activities.
• Collaborating with the steering committee members to generate educational material on HLA and KIR immunogenetics including background information on their project, review articles, webinars, and relevant SOPs for a public-facing website.
• 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 NIH Project Scientist(s) will provide guidance to the recipients on monitoring research progress; provide scientific input; identify resources that HLA and KIR RGC may leverage; and provide oversight and monitoring of the collaborative research.
• NIH Project Scientist(s) will coordinate NIH staff assistance, including interactions with ImmPort and provide assistance with the design of the Steering Committee technical and management activities including being a voting member of the steering committee.
• The NIH reserves the right to terminate or curtail a study in the event of a substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the approved project. Future year funding may be negotiated downward depending on the progress towards achieving the previously agreed upon research goals, interim objectives and annual milestones.
• 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 board of the HLA and KIR RGC. All Consortium investigators will be required to accept and implement common guidelines and procedures approved by the Steering Committee. 

• The voting members of the Steering Committee will include the contact PI from each U01 and the NIH Project Scientist. Additional PDs/PIs and NIH Program Officer(s) will serve as non-voting Steering Committee members.
• NIH may appoint up to two external scientists or additional staff to the Steering Committee as non-voting members. The Steering Committee may appoint additional non-voting members by majority vote.

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.

3. Data Management and Sharing

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.

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. 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.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (Responsibility/Qualification in SAM.gov, formerly FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Shilpa Kulkarni, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-747-7365
Email: shilpa.kulkarni@nih.gov 

Ursula Utz, Ph.D.
National Institute of Neurologic Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: utzu@ninds.nih.gov 

Maryam Rohani, D.D.S., Ph.D.
National Institute of Allergy and Infectious Diseases(NIAID)
Telephone: 301-761-6656 
Email: maryam.rohani@nih.gov 

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email:ChiefGrantsManagementOfficer@ninds.nih.gov

Deo Gunza
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-6092
Email: deo.gimza@nih.gov 

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email:ChiefGrantsManagementOfficer@ninds.nih.gov 

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.