It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

This Funding Opportunity Announcement (FOA) for the Human Immunology Project Consortium (HIPC) solicits applications from single institutions or consortia of institutions to participate in a network of human immunology profiling research groups in the area of infectious diseases, including HIV. Applications are sought that propose to employ established and recent advances in immune profiling technologies to study the human immune system (1) before and after vaccination against an infectious pathogen; (2) before and after administration of a vaccine adjuvant that selectively targets immune components; and (3) during or following naturally-occurring infection. Studies supported under this FOA will measure the diversity and commonalities of human immune responses under a variety of conditions and over time using high-throughput systems immunology approaches coupled with detailed clinical phenotyping in well-characterized human cohorts. In order to gain a comprehensive understanding of human immunity, cohorts may include vulnerable populations such as older adults, children, pregnant women, under-represented minorities, and individuals with immune-mediated conditions (autoimmune diseases, atopic diseases) or who have received tissue/organ transplants. Inclusion of these populations will allow HIPC to contribute to our understanding of these conditions.

The major goals of this program are to: (1) support longitudinal analysis of human immune responses in clinically well-characterized cohorts to determine how these profiles are perturbed and eventually returned to a new homeostatic state after challenge with an antigen (e.g., vaccination or natural infections) and/or adjuvant(s); and (2) develop molecular signatures that define immune response profiles and/or identify biomarkers across the lifespan that correlate with the outcomes of vaccinations, adjuvants or natural infections in humans. An additional goal of this program is to advance research by promoting rapid public access to HIPC-supported data and meta-data through public portals such as ImmPort.

A companion FOA (RFA-AI-20-080) will support development and operation of a HIPC Coordinating Center (U01) that will be responsible for coordinating cross-HIPC data integration, analysis, and visualization; development and maintenance of a public HIPC website/knowledgebase to support cross-HIPC data analysis and visualization; and fostering collaborations amongst HIPC-funded investigators through management of HIPC subcommittees and through an opportunity fund to support cross-collaborative studies.

One approach to building a deeper understanding of human immune system activation and regulation is the systems biology approach, which involves the rigorously controlled, unbiased, and quantitative collection of large data sets that are then integrated to create models of complex molecular and cellular interactions that can provide insights into how the immune system functions as a whole and how it interacts with other biological functions. NIAID’s investment in systems biology spans nearly 20 years and includes programs to discover new immune response genes and mechanisms important for protection from infectious and immune-mediated diseases using animal models, development of computational models of immunity, and systems biology of infectious diseases. System level data may be generated from omics technology platforms such as genomics, spatial genomics, epigenomics, transcriptomics, RNAi screens, proteomics, metabolomics, lipidomics, glycomics, and systems serology to study human tissues and cells. Advances in bioinformatics have made the analysis of large integrated data sets possible, although more work is still needed in the areas of bioinformatics, computational modeling, and biostatistics to improve data management and analytical capabilities that will allow even richer mining and knowledge generation from the data generated in such studies. The results of systems immunology studies create a foundation for future hypothesis-driven research to test the functional importance of different system components and to identify potential targets for development of new vaccines or therapeutics.

The Human Immunology Project Consortium (HIPC) was established in 2010 and renewed in 2015 and 2017. Seven U19 awards were made in 2010 and the current program consists of nine sites, each supported by the U19 cooperative agreement mechanism. This program also supported the development of a HIPC-specific knowledgebase, ImmuneSpace, for visualization and analysis of HIPC-related human immune profiling data sets. Over 1000 publications reference HIPC funding, and data from 91 HIPC studies are publicly available through the ImmPort repository. In addition, cross-HIPC collaborations have resulted in updates to the Cell Ontology (http://www.obofoundry.org/ontology/cl.html) regarding immune cell subsets and the development of a framework to capture and disseminate immune transcriptional signatures (http://hipc-dashboard.org) to the broader research community. Another HIPC achievement is the development of a standardized approach to clinically characterize participants in HIPC-supported studies (HIPC Clinical Database: Adult and HIPC Clinical Database: Pediatric).

This initiative is a renewal of the HIPC program to support longitudinal immune profiling of individuals receiving licensed vaccines or naturally exposed/infected with pathogenic organisms, as well as individuals participating in vaccine/adjuvanted vaccine clinical trials or controlled human pathogen challenge studies funded by other mechanisms.  Investigators funded under this program also will utilize the immune profiling data to develop and validate overall immune signatures associated with disease outcomes or vaccine efficacy, as well as signatures that may characterize the responses of a particular population (e.g., older adults, younger children, individuals with atopic or autoimmune conditions or who have received tissue/organ transplants.)

While this program will not support clinical trials requiring an Investigational New Drug (IND) authorization or IND equivalent, it will support clinical trials that do not require an IND. In addition, this program will support clinical studies using U. S. Food and Drug Administration (FDA) approved interventions (e.g., licensed vaccines) that are prescribed for use per indication (as described in the intervention’s product label) and are exempt by regulatory authorities from needing an IND.  Applicants should directly contact the FDA or the equivalent non-US regulatory authority (if applicable) to discuss whether an IND (or equivalent) application is required and obtain a waiver if it is required. NIAID reserves the right to decide whether a proposed clinical trial is responsive to the FOA based on the definitions and guidance provided herein. To clarify any clinical trial related matter, applicants are strongly encouraged to contact the Scientific/Research Contacts listed in Section VII of this initiative. When clinical studies are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study (https://www.niaid.nih.gov/research/guidance-policies-and-standard-operating-procedures). An updated NIAID policy was published in the NIH Guide on July 8, 2002, and is available at: https://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html.  The full policy, including terms and conditions of award, is available at: https://www.niaid.nih.gov/grants-contracts/niaid-clinical-terms-award.     

The individual HIPC U19 awardees will be responsible for conducting immune profiling studies and developing and validating immune signatures associated with disease outcomes and vaccine efficacy, including identification of immune correlates of protection or disease progression/pathogenicity.

Examples of research areas of interest include, but are not limited to:

• Measurement of dynamic, longitudinal changes in immune profiles following vaccination, adjuvant administration, or natural infection with a pathogen that correlate with clinical outcome.
• Comparison of longitudinal immune profiles among ethnically diverse or special populations (e.g., infants, neonates, older adults, atopic individuals, transplant recipients, patients with autoimmune disease) after natural infection or administration of a vaccine or adjuvant, including examination of differential responses in males versus females.
• Analyses of cellular populations and tissue/organ compartments associated with development and maintenance of long-term immunological memory to infection and vaccination.
• Identification of immune profiles that correlate with vaccine efficacy or surrogates of efficacy.
• Comparison of immune profiles in vaccinated populations to immune profiles in populations with naturally acquired infections.
• Identification of markers of mucosal, tissue/organ or skin immune responses that reflect or contrast with markers of systemic response.
• Systems serology and other high throughput characterization of humoral immunity.
• Dissociation of markers of protective immunity from markers of vaccine toxicity/reactogenicity.
• Examination of the role of the human microbiome in modifying immune responses to vaccinations or natural infections.

For HIV-related research:

HIV-focused applications are defined as: Immune profiling applications that focus entirely on HIV immunogens (i.e., HIV infection or individuals receiving HIV vaccines (+ or - adjuvant)). The key requirement for HIV applications should be a coherent set of interrelated research aims with a clear overall focus on the use of immune profiling to advance research progress toward a safe and efficacious HIV vaccine. In that context it would be acceptable to propose work with non-HIV immunogens to address specific knowledge gaps about HIV vaccine design by obtaining comparative information from immune responses to HIV and non-HIV immunogens. Examples of HIV-related studies include, but are not limited to:

• Measurement of dynamic changes in immune profiles following natural coinfection or superinfection with two or more distinct HIV viruses that correlate with favorable immunological and/or clinical outcome.
• Studies of immune responses to HIV vaccine candidates on an IND (where the clinical trial is supported and conducted by sources outside HIPC). Examples of specific areas of HIV vaccine research interest include:
• identifying the epitopic specificity and other qualities of antibody responses that can provide protective immunity by inducing durable broad-coverage virus neutralizing antibody responses, or inducing durable, broad-coverage antibody responses with other specific, protective antiviral function(s); or examination of the developing role of Fc receptors in HIV vaccine antibody responses;
• exploring vectors/adjuvants/delivery technologies that facilitate the induction of different qualities and specificities of durably protective antibody responses;
• studying envelope isolates, constructs, modifications, fragments, combinations and sequences to induce broadly protective antibody coverage;
• determining the role of baseline inflammation in shaping HIV-vaccine induced innate and adaptive immunity; exploring pre-vaccination interventions, such as probiotics or anti-inflammatory drugs, to steer immune responses to yield effective protection.

All proposed research (non-HIV and HIV-focused applications) must include unbiased, data-gathering, quantitative systems biology experimental approaches with human samples (e.g., genomics, epigenomics, transcriptomics, RNAi screens, proteomics, metabolomics, lipidomics, or glycomics) and correlate results with outcomes of infection or vaccination. Frequent, prospective, and longitudinal sampling linked with deep clinical phenotyping is strongly encouraged to enable the study of dynamic changes and identification of biomarkers.

• Each proposed project must generate human immune response profiles using primary human immune cells or tissues obtained (1) during or after infection, (2) before and after vaccination against an infectious disease (s), and/or (3) before and after administration of an adjuvant that targets an immune component.
• Cohorts must be developed with individuals receiving licensed vaccines according to label or receiving standard clinical care for infection. Alternatively, samples may be used from cohorts participating in independently funded clinical trials of vaccination or infection.
• A project also may propose to develop new assays or statistical or bioinformatics tools relevant to that project and to the central theme of the application, but this is optional.

Since the multi-project U19 cooperative agreement mechanism is being used, the projects proposed within each application are expected to be synergistic.  For the purpose of this FOA, synergy will be defined by the creation of a whole that is greater than the sum of its parts in terms of advancing our understanding of the human immune response to vaccines, adjuvants, and/or natural infection.  For example, a synergistic application may use different infections, vaccines or adjuvants as immune triggers to examine common hypotheses or employ common analysis methods to identify shared or unique mechanisms of immune-mediated protection or pathogenesis, especially where novel findings in one area or experimental system prompt new research in a different area or experimental system that would not have happened without close collaboration.

Each award will contribute to the rapid dissemination of human immune profiling data to the wider scientific community through ImmPort or other public portals designated by NIAID. To promote rapid public access to HIPC-supported data and results, all HIPC Program Directors /Principal Investigators (PDs/PIs) funded under this initiative will work closely with ImmPort staff for data submission and with the HIPC Coordinating Center for development of cross-HIPC integrated data analysis, presentation, and visualization. Furthermore, for the clinical characterization of participants in HIPC-supported studies, all HIPC investigators funded under this initiative will have to collect medical information that is compatible with and will be entered into the HIPC clinical characterization system (HIPC Clinical Database: Adult and HIPC Clinical Database: Pediatric).

All HIPC investigators must share their HIPC-supported data and meta-data publicly through ImmPort, data analysis and visualization portals offered by the HIPC Coordinating Center, or other public portals designated by NIAID, consistent with achieving the goals of the program (current HIPC data sharing policy available at https://www.immuneprofiling.org/hipc/page/showPage?pg=dataShare). Privacy of participants will be safeguarded, and confidential, and proprietary information will be protected. Prior to award and data collection, dataset definitions and schedules for data sharing will be negotiated with NIAID as appropriate, as will plans for other resource sharing. It is expected that all HIPC-supported data submitted to ImmPort or other public portals will be released within 9 months to 1 year of submission or upon publication, whichever comes first.

This program is milestone-based and includes the flexibility to quickly redirect or replace research projects during the funding period. Funding beyond the first year may be negotiated downward depending on the progress in meeting the data- and other resource-sharing milestones negotiated with NIAID after award, consistent with achieving the goals of the program.

Steering Committee

To promote scientific collaboration, exchange of scientific findings among HIPC centers, and coordination of data dissemination to the broader scientific community, a HIPC Steering Committee will be established and serve an advisory role for the entire HIPC collaborative research program. Each HIPC center will be represented by one PD/PI as a voting member of the HIPC Steering Committee. In addition, the Director of the HIPC Coordinating Center (U01) will be a voting member, while NIAID Project Scientists will be non-voting members.

External Advisory Board (EAB)

An EAB will be convened by NIAID to review, evaluate, and prioritize the scientific progress of the individual HIPC awardees and the Consortium as a whole. EAB members will be selected by NIAID after award and potential EAB members should not be proposed or contacted by applicants.  

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

• Examination of pathogen-specific immune responses where the primary focus of the application is for vaccine research, design or development/testing, or to understand microbial pathogenesis or microbial mechanisms to evade host immunity.
• Immune profiling studies in atopic, autoimmune, or transplant patients in the absence of analysis of responses to natural infections, vaccinations, or adjuvants.
• Clinical trials requiring a regulatory application (e.g., IND from the US FDA or other equivalent non-US regulatory authority). This definition includes studies that utilize experimental exposures to infectious agents.
• Any animal studies, including studies that use animal models of human diseases or studies that employ humanized mice.
• Systems biology studies of a microbiome(s) in the absence of systems immunology/profiling studies of human immune tissues, cells, or molecules in response to infectious pathogens, adjuvants, or vaccines.
• Studies using only transformed human cell lines.
• Immunologic profiling or epidemiologic studies that focus on a single timepoint and are not coupled with post-exposure, prospective, longitudinal, repeat measure sampling.
• Studies that focus on Genome Wide Association Studies (GWAS) in the absence of comprehensive immune profiling.
• Studies on infectious agents used as therapeutics, such as viral vectors for antibody delivery.
• Projects that do not include an assessment of human immune profiles in the context of human immunologic or infectious disease, measured in primary human immune cells or tissues in response to vaccination, naturally acquired infection, or treatment with adjuvants.

Individual HIPC Organizational Structure

Each HIPC center must include: Research Projects (minimum of 2, maximum of 3), an Administrative Core, a Data Management and Analysis Core, and a Clinical Core. Service Cores (e.g., transcriptomics, multi-parameter flow cytometry, etc.) are optional and limited to no more than 3. 

Research Projects

Research Projects will be multi-disciplinary, synergistic projects organized around a central scientific theme focused on human immunology profiling and immune signature or biomarker discovery.

No more than one of the proposed research projects within an application may examine immune responses to SARS-CoV-2, influenza, or dengue vaccination or natural infection.  For example, applicants may include one project that studies responses to SARS-CoV-2 and one project that studies responses to dengue or influenza, if appropriate for their program goals, but may not submit an application that contains 2 or more projects on only one of these pathogens. In addition, projects on seasonal or related coronaviruses may be included in applications that also have a SARS-CoV-2 project, if appropriate. Potential applicants are strongly encouraged to consult with the Scientific/Research Contact listed in Section VII during the early stages of preparation of the application. 

Administrative Core

The Administrative Core will support the coordination of efforts across the center's research projects and cores, and activities to advance integration into the broader HIPC network. This core will be responsible for organization, management, decision-making, and periodic evaluations within the individual HIPC center, involvement of institutional and programmatic resources, and shared publications. This Core is expected to create and implement administrative and leadership mechanisms that will foster effective interactions within center investigators and with other HIPC network PDs/PIs and institutions to promote synergistic research efforts.

Data Management and Analysis Core

This Core will provide central data storage, data management, and information security services to all researchers within the center, and will be responsible for ensuring the timely submission of data and data analyses obtained under this award to the ImmPort database or other public databases recommended by NIAID. In addition, this Core will provide bioinformatics expertise and data integration and analysis support, including computational modeling if necessary, for the discovery and validation of immune signatures or biomarkers application.  The Core may also include study design and statistical support/services for the researchers within the center. The Core Leader, or their designee, will represent the HIPC center in a HIPC Data Management and Integration Sub-Committee that will operate under the HIPC Coordination Center to promote cross-HIPC collaboration including refinement of data standards, and data analysis and integration methods and for further development or validation of immune signatures or biomarkers associated with disease or vaccination outcomes. 

Clinical Core

This Core will ensure a standardized approach in the recruitment and clinical characterization of human subjects in all studies that will be conducted by the HIPC center in accordance with the HIPC clinical characterization system (HIPC Clinical Database: Adult and HIPC Clinical Database: Pediatric).   In addition, the Core will be responsible for implementing appropriate human subject protection measures, including cGCP rules, across all studies.  This will require that the Core ensures appropriate training of personnel and monitors all clinical study activities of the HIPC center.  In this context, the Core will conduct functions such as clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the HIPC center will conduct, development of protocol-specific case report forms, training of clinical personnel prior to protocol initiation (both cGCP and protocol-specific training), preparing IRB applications and other approval processes, preparing annual progress reports to the IRB and NIH, monitoring of the clinical component of the study, capturing and reporting adverse events related to any intervention or procedure, handling protocol deviations, and supporting the Data Management and Analysis Core in clinical data cleaning.  The Core Leader will represent the HIPC center in a HIPC Clinical Sub-Committee that will operate under the HIPC Coordinating Center to promote cross-HIPC collaboration including sharing SOPs, documents, and samples as appropriate. 

Service Core(s)

These Cores are limited to providing standard assays, reagents, technologies, repositories, or other available services to investigators. They are intended to provide the HIPC center Research Project investigators with resources and services that already exist and are well characterized for use by at least two projects. Service Cores will not propose the development of new technologies nor conduct any hypothesis-driven research. Each Service Core must provide support for at least two Research Projects.

Applicants are encouraged to visit the Frequently Asked Questions site at: https://www.niaid.nih.gov/grants-contracts/questions-answers-RFA-AI-20-079.

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

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

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)

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)
• 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 Institutions) 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 SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

Note that the multiple PD(s)/PI(s) option may be used only for the Overall Program. Projects are limited to a single project lead per project and a single core lead per core within the multi-component application.

An individual can be PD/PI on only one application, including multiple PD/PI applications.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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 NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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:

Thomas Conway, Ph.D.
Telephone: 240-669-5075Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core	6 pages
Clinical Core	12 pages each
Data Management and Analysis Core	12 pages each
Service Core(s)	6 pages each
Project(s) (Use for Research Projects)	12 pages each

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Clinical Core: required, maximum of 1: must support all Projects
• Data Management and Analysis Core: required, maximum of 1: must support all Projects
• Service Core: optional, up to 3: each core must support at least 2 Projects
• Research Projects: required, minimum 2, maximum 3

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

Applicants should provide evidence that demonstrates the PD(s)/PI(s)'s abilities and capabilities to provide leadership, guidance and direction over the proposed project. Provide evidence that the PD(s)/PI(s) have prior experience in the research areas proposed and highlight accomplishments in the field.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Briefly describe the overall specific aims of the proposed program. 

Research Strategy: Summarize the overall research strategy for the HIPC center application and explain how the proposed program satisfies the purpose and objectives of this FOA. Explain how the proposed research projects are synergistic and fit under the overarching program theme. The HIPC application should be viewed as a confederation of interrelated projects, each capable of standing on its own scientific merit, but complementary to and synergistic to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Highlight the overall synergy across the proposed projects and cores to advance our understanding of human immune responses to infection, vaccination or adjuvants.  For the purpose of this FOA, synergy will be defined by the creation of a whole that is greater than the sum of its parts in terms of advancing our understanding of the human immune response to vaccines, adjuvants, and/or natural infection. 

Clinical Studies or Trial Overview: For applications that include clinical trials or clinical research on human immune responses that span multiple components, explain how the proposed clinical trials or clinical research will support the program’s common theme; how samples will be used across/within relevant project(s) and/or core(s); and how sample distribution and communication will be managed throughout the proposed program.

Letters of Support: Provide any institutional letters of support specific to the Overall Component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan, but it is not applicable to this component. The Data Sharing Plan should be submitted only in the Data Management and Analysis Core. See instructions in the Data Management and Analysis Core.
• Awardees must deposit data and data analyses into ImmPort or other public data portal as designated by NIAID.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Clinical Core component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Administrative Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• Request funds to support the travel of the PD(s)/PI(s) and up to three (3) relevant staff to attend semi-annual face-to-face meetings to be held in the Rockville, MD area and organized by the NIAID Project Scientists (2 meetings per year and 2 full days per meeting).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the activities and services of the Administrative Core. Describe the work to be completed to address issues of program coordination, communication, and management.

Research Strategy: Provide a staffing and administrative plan that includes a discussion of the structure and roles of administrative and scientific staff for the core, including: the training and experience of proposed staff and the functions to be performed; and how resources will be prioritized, allocated, and managed. Provide a management plan for fiscal accountability and communication within the program.  

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan, but it is not applicable to this component. The Data Sharing Plan must be submitted only in the Data Management and Analysis Core. See instructions in the Data Management and Analysis Core.
• Awardees must deposit data and data analyses into ImmPort or other public data portal as designated by NIAID.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• Request funds to support all functions of this core including clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the HIPC U19 center will conduct, development of protocol-specific case report forms, training of clinical personnel prior to protocol initiation (both cGCP and protocol-specific training), monitoring of the clinical component of the study, capturing and reporting adverse events related to any intervention or procedure, handling protocol deviations, supporting the Data Management and Analysis Core in clinical data cleaning. 
• Request funds to support the travel of the Core Lead, and - at the discretion of the Core Lead- up to three (3) additional scientific staff, to attend semi-annual face-to-face meetings to be held in the Rockville, MD area and organized by the NIAID Project Scientists (2 meetings per year, 2 full days per annual meeting).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the proposed activities and services of the Clinical Core. Describe the work to be completed indicating the core’s relationship to the program’s goals. The Clinical Core must support the activities of all of the Research Projects.

Research Strategy:

• Explain how the Core will serve the proposed research projects. For example, describe core activities to provide a uniform screening and characterization of potential participants in the studies proposed by each of the center’s research projects. 
• Describe the clinical outcomes that will be captured and the methodologies that will be used. Clearly indicate that the HIPC clinical characterization template will be used to collect participant clinical information in any study supported by HIPC (HIPC Clinical Database: Adult and HIPC Clinical Database: Pediatric). 
• Describe processes and procedures for clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the HIPC center will conduct, development of protocol-specific case report forms, training of clinical personnel prior to protocol initiation (both cGCP and protocol-specific training), preparing IRB applications and other approval processes, preparing annual progress reports to the IRB and NIH, monitoring of the clinical component of the study, capturing and reporting adverse events related to any intervention or procedure, handling protocol deviations, supporting the Data Management and Analysis Core in clinical data cleaning.

Letters of Support:

• Provide any letters of support from collaborators that are specific to the Clinical Core.
• Provide the memorandum of understanding from the clinical trial sponsor(s), IND holder(s), and Principal Investigator(s). The memorandum of understanding will confirm agreement among the various parties and will outline their agreement in the following areas: (1) ownership, analysis, access, and release of data from the proposed immune profiling studies; (2) access to the data from the parent clinical trial (how/when) that is needed to analyze the data generated by the proposed profiling studies, including procedures for prevention of unblinding of the parent trial; (3) statement that study approved by IRB or documentation that IND was obtained; (4) intellectual property management; and (5) publication of the proposed profiling study results. For the publication of HIPC-supported immune profiling results, the memorandum should indicate that all parties agree that HIPC data sharing and publication policies will be followed.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan, but it is not applicable to this component. The Data Sharing Plan must be submitted only in the Data Management and Analysis Core. See instructions in the Data Management and Analysis Core.
• Awardees must deposit data and data analyses into ImmPort or other public data portal as designated by NIAID.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Note: For all clinical research or trial protocols and procedures that span multiple Research Projects, enter requested information in the PHS Human Subjects and Clinical Trials Information section associated with the Clinical Core, not the Overall component. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information Forms across components. Human subject details that are specific to a particular Research Project should be entered in the PHS Human Subjects and Clinical Trials Information Forms in the appropriate Research Project component.

Other Requested Information:  All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

If the Clinical Core supports projects proposing the use of human samples to be obtained from independently-funded clinical trials, the following materials MUST be included in a single pdf attachment named, "Human Samples Information.pdf";

• synopsis of the parent clinical trial protocol(s)
• blank informed consent forms for the parent clinical trial(s)
• blank informed consent forms for the proposed immune profile studies, if different from the parent trial(s)
• reference to the ClinicalTrials.gov citation(s), if applicable
• description of events including the volume of blood, or amount of tissue, collected for the proposed immune profile studies

Note: The materials from the independently funded clinical trials should identify the Research Projects they will provide with tissue samples. Applications lacking this attachment will be considered incomplete and will not be reviewed.

To the extent permitted by applicable laws and regulations, NIH will treat as confidential trial information that the trial sponsor marks "Confidential." Copies of the informed consent form(s) for the proposed additional studies, if different, must also be included.  It is recommended that applications submitted under this FOA have clear language in the informed consent form(s) that distinguishes proposed immune profiling studies from the clinical trials with which they are linked.  It is also recommended that the following items be clarified in the consent form: (1) additional blood or tissue that will be collected as part of the proposed profiling study; (2) the right of the subjects to refuse to participate in the proposed profiling study and still participate in the parent clinical trial; (3) that no charges to the subject for participation in the proposed profiling study are incurred; and (4) agreement to share the subject s de-identified data obtained from the immune profiling study as well as the parent trial. Any incentives provided to subjects to participate in the proposed profiling study, if in addition to those under the parent clinical trial, should be clearly described and justified. If the information provided about a clinical trial, as described above, contains proprietary information of commercial value, applicants are strongly advised to follow all applicable instructions for proprietary information in the SF424 application.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• Request funds to support central data storage, database security, data management and analysis for the entire awarded U19 cooperative agreement to all researchers within the applicant group.
• Request funds to support the timely submission of data and data analyses to the ImmPort and for the Core lead/their designates to work with the HIPC Coordinating Center (companion U01 award, RFA-AI-20-080) to coordinate HIPC data submission standards, including use of common controlled vocabularies and ontologies to make data more findable, accessible, interoperative and reproducible (FAIR principles). For reference, the current HIPC data sharing policy is available at: https://www.immuneprofiling.org/hipc/page/showPage?pg=dataShare.

Request funds to support the travel of the Core Lead, and at the discretion of the Core Lead up to three (3) additional scientific staff, to attend the annual face-to-face meetings to be held in the Bethesda, MD area and organized by the NIAID Project Scientists (2 full days per annual meeting). 

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the broad, long-range activities and services of the proposed core, indicating the core’s relationship to the program’s goals. The Data Management and Analysis Core must support the activities of all of the Research Projects. 

Research Strategy:

• Describe the overall function of the Core and describe how the services of this Core will support and advance the outcomes from the proposed research program.
• Explain the role of this Core in the research program. Discuss how the Core will support and facilitate data management, data analysis, and data sharing. In regards to data sharing, the explanation should describe how the Core will meet the requirement for all HIPC investigators, including any scientists that may be added post-award as a result of support from the HIPC Coordinating Center, to share their HIPC-supported data publicly through ImmPort or other public portals designated by NIAID.
• Discuss the staffing plans that will support the functions associated with this Core, including any professional staff or staff with specialized skills to fully address the extent of Core needs.
• Describe the processes, procedures, methods and plans to provide the bioinformatics infrastructure support for the following:
• Statistical consideration of study design;
• Data collection, cleaning, and tracking;
• Database infrastructure;
• Information management and monitoring;
• Management of complex cross-sectional or longitudinal data;
• Computational modeling (as needed);
• Statistical analysis and data integration methods.
• Describe how the Core staff will apply data or statistical analyses to ensure studies (especially those with small sample sizes, or descriptive data) are adequately powered and interpreted. If primary study results will be descriptive in nature, the methods that are used should ensure sufficient precision in the proposed estimates. If primary hypotheses are being formally tested, applicants must demonstrate sufficient statistical power to elucidate key differences that support these primary hypotheses.
• For clinical studies, the descriptions of sample size calculations in the Research Strategy section should satisfy the following conditions (Do not duplicate any information in the PHS Human Subjects and Clinical Trial Information section):
• For sample size calculations, as well as for data analysis and integration, provide justification for the planned sample size to illustrate that it is sufficient to provide meaningful information regarding immune responses to infections or vaccines.  If the primary study results will be descriptive in nature, this justification should entail ensuring there is sufficient precision in these estimates. If a primary hypothesis is being formally tested, applicants must demonstrate sufficient statistical power to detect key differences that support the primary hypothesis. In many settings, it will be appropriate to justify the sample size both with respect to hypothesis testing and in descriptive studies.
• For studies where the primary outcomes are descriptive in nature (such as estimation of immune response to a vaccine or natural infection), expected confidence interval widths should be given. These confidence interval widths ideally should be based on previous data, which must be cited.  If such data are not available, confidence interval width should be presented as a function of a range of plausible data characteristics (such as standard deviation).  The confidence interval width should reflect a reasonable level of accuracy of the estimate.
• For studies focused on hypothesis testing (such as testing for association between potential biomarkers and post-vaccine immune markers), power calculations should be provided for the primary hypothesis test(s). These calculations ideally would be based on cited historic data.  When no such data are available, the powers across a plausible range of data characteristics (such as effect size and standard deviation) should be presented. Typically, power calculations should suggest that the planned sample size will yield at least 80% power to detect the relevant effect size at the specified alpha level.

Letters of Support: Provide any letters of support from collaborators that are specific to the Data Management and Analysis Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, must provide a Data Sharing Plan. As part of the Data Sharing Plan, applicants should detail the procedures for sharing, release, and access of the data and data analyses generated under all projects supported by this application to the broader scientific community in adherence to the requirements and timelines described in the NIAID Data Management and Sharing Guidelines (https://www.niaid.nih.gov/research/data-sharing-guidelines ).
• Awardees must deposit data and data analyses into ImmPort or other public data portals as designated by NIAID. The Data Sharing Plan must ensure that the data are Findable, Accessible, Interoperable, and Reusable (FAIR) per the NIAID Data Sharing Guideline at https://www.niaid.nih.gov/research/data-sharing-guidelines, as appropriate and consistent with achieving the goals of the program.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• Request the percentage of funds that will be required to support each research project that will utilize the core.
• Request funds to support the travel of each Core Lead, and - at the discretion of the Core Lead- up to three (3) additional scientific staff per core, to attend semi-annual face-to-face meetings to be held in the Rockville, MD area and organized by the NIAID Project Scientists (2 meetings per year, 2 full days per annual meeting). 

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the broad, long-range activities and services of the proposed Core. In addition, state the Core’s relationship to the program’s goals and how the Core will support the research that is proposed by two or more individual research projects in the application.  

Research Strategy: A Service Core must be used by at least two of the Research Projects. Indicate the specific research projects to be served by the core and explain why the core resources are not otherwise available. Provide information, including validation data and advantages/disadvantages compared to other methodologies, and appropriate references on the methodology of the specific service (assays/tests) that the Core will use, as well as alternative approaches in case problems are encountered. Any proposed development of new technologies, assays, etc. must be presented within a research project and not in a service core.    

Letters of Support: Provide any letters of support from collaborators that are specific to the Service Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan, but it is not applicable to this component. The Data Sharing Plan must be submitted only in the Data Management and Analysis Core. See instructions in the Data Management and Analysis Core.
• Awardees must deposit data and data analyses into ImmPort or other public data portal as designated by NIAID.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

• In cases where samples for human immune profiling are to be collected from an independently-funded clinical trial, the costs of additional clinical trial-related activities such as the costs of re-consenting study participants, preparation of protocol or IND amendments, and additional sample collection, preparation, and shipping may be included in the relevant project budgets.
• Request funds to support the travel of each Project Lead, and - at the discretion of the Project Lead- up to three (3) additional scientific staff per project, to attend semi-annual face-to-face meetings to be held in the Rockville, MD area and organized by the NIAID Project Scientists (2 meetings per year, 2 full days per meeting). 

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List the broad, long-range objectives and goals of the proposed project. Describe the work to be completed. In addition, state the individual project’s relationship to the U19 program’s goals and how the project relates to other projects or cores to create synergy.  

Research Strategy: A project must focus on longitudinal human immune profiling of infection, vaccination, or vaccine adjuvant administration in well-characterized populations, and analysis and validation of the profiling data for development of immune signatures and identifying biomarkers associated with vaccination or disease outcomes. Each project should address a common immunological theme such that synergy is clearly evident among all the proposed research projects. Each project must propose studies with primary human immune cells or tissues.

Describe how the proposed research will contribute to meeting the program’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project’s relevance to the primary theme of the application and how it will synergize with the other projects and cores. Include results from preliminary work to support the study design and U19 program and individual project goals.

HIV-focused applications must describe how the chosen non-HIV immunogens (if used) will provide comparative information that facilitates HIV vaccine design.

Required Elements: All applications must describe:

• Unbiased, data-gathering, quantitative systems biology type experimental approaches used for longitudinal analysis of human sample sets;
• Highly characterized human participant cohorts from which samples will be obtained. Use of a table or chart format is encouraged to summarize the clinical samples and cohorts to be used in the project;
• How sample analyses will be associated with outcomes of infection or vaccination (e.g., duration and severity of illness, antigen-specific antibody levels, or cytotoxic T cell responses, etc.), and lead to development of correlative immune signatures or biomarkers.

Recommended Contents: It is strongly recommended that applications include the following clinical trial or study information either in the PHS Human Subjects and Clinical Trials Information Form or the Project Research Strategy Section. Selected details for clinical trials and clinical studies will be captured using the PHS Human Subjects and Clinical Trials Information Form. Additional information should be included in the Project Research Strategy Section, but do not include information in the Research Strategy section that duplicates study details requested in the PHS Human Subjects and Clinical Trials Information Form:

• Provide a plan for the proposed clinical study or clinical trial that meets the objectives of the FOA. Present sufficient detail to convey the goals of and design approach to the study or trial and include the rationale for the human population(s) chosen to be studied, the types of samples proposed, collection times, availability of study subjects and/or number of samples (e.g. cells or tissue) available.
• For each research question that the project addresses, describe and justify the required number of samples to be collected and analyzed.

Milestones and Timelines: Describe quantifiable milestones by year as well as annual timelines for the research project. Milestones should not be a restatement of the aims; rather, they should specify the outcome(s) for major research activities and be scientifically justified. The Milestones and associated Timelines may be represented using a Gantt chart or equivalent tool.

Letters of Support: Provide any letters of support from collaborators that are specific to the research project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• Each Project should include a detailed description of the resources (model organisms or genomic data), to be generated and how they will be shared with the broader research community, based on the scope of the Project.
• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan, but it is not applicable to this component. The Data Sharing Plan must be submitted only in the Data Management and Analysis Core. See instructions in the Data Management and Analysis Core.
• Awardees must deposit data and data analyses into ImmPort or other public data portal as designated by NIAID.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

The study record(s) must be included in the PHS Human Subjects and Clinical Trials Information section of the Research Project where the work is being done, unless the same study spans multiple Research Projects. To avoid the creation of duplicate study records, a single study record with sufficient information for all Research Projects must be included in the PHS Human Subjects and Clinical Trials Information Forms in the Clinical Core component when the same study spans multiple Research Projects. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials section across components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

See Part 1. 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.

Part I. Overview Information 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) using ASSIST or other electronic submission systems. 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 Policy on Late Application Submission.

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 SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) 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.

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

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.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific for this FOA

• Is the application as a whole scientifically compelling?
• Is the application adequately focused on immune profiling and development of immune signatures/biomarkers associated with vaccine or disease outcomes?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA

• Is the application cohesive with respect to projects and cores fitting into a common theme towards achieving the central objectives?
• Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Overall Impact - Research Projects

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for each 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).

Scored Review Criteria - Research Projects

Reviewers will consider each of the review criteria below in the determination of scientific merit, and each individual research project will be given a separate score. 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the project leaders, collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in human subjects?

Specific for this FOA

• Are the proposed milestones and timelines appropriate and feasible?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Overall Impact - Administrative, Clinical, Data Management and Analysis, and Service/Resource Cores

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for each Core to meet its intended goals in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Review Criteria - Administrative, Clinical, Data Management and Analysis, and Service/Resource Cores

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core but will not give separate scores for these items.

Administrative Core

• Are the staffing and administrative plan appropriate to facilitate attainment of the objectives of the proposed program? Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core and the overall program?
• Is the plan to organize communications, group meetings, and teleconferences adequate and appropriate? Are the plans for coordination, problem identification and resolution, and establishment of a strong collaborative environment for the program appropriate?
• Are the plans for resource allocation within the program adequate and appropriate?
• Is the management plan for fiscal accountability and communication within the program appropriate?

Clinical Core

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are sufficient staff effort and expertise dedicated to support the proposed Core duties?
• Is there sufficient clinical infrastructure to support the proposed activities?
• For proposed clinical studies, are the following appropriate and feasible:
• The timeline for protocol development and implementation
• Plans for recruitment and retention of study participants
• Facilities and services of proposed study site(s)
• Safety monitoring and plans for management and analysis of study data?

Data Management and Analysis Core

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are sufficient effort and expertise dedicated to data management, data analysis, integration and sharing methods?
• Is there sufficient bioinformatics infrastructure to support the proposed activities?
• Are the study designs, statistical analyses and computational modeling (if applicable) methods sound and will they meet the needs of the individual projects and overall program?
• Are the plans for managing complex cross-sectional or longitudinal data suitable for the individual projects and overall program?
• Are the plans for data sharing and transfer to ImmPort or other public portals designated by NIAID appropriate and adequate to ensure that NIAID-funded data will be Findable, Accessible, Interoperable, and Reusable (FAIR)?

Service/Resource Core(s)

• Is provision of the proposed core services to two or more Research Projects critical and justified?
• Is there a clear relationship of the Core to the central scientific theme of the overall program?
• Are the relevant facilities or services provided (including procedures, techniques, quality control) and criteria for prioritization of usage appropriate?
• Are the proposed personnel appropriate to lead and staff the Core? Is the commitment of the Core Leader and other staff sufficient?

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.

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Sharing Model Organisms; and 2) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

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 policy and procedures, 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:

• 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.
• Will receive a written critique.

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

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 FOA. 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.

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.

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.

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.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm.

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex.  This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that 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 FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency.  Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment.  Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws.  Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions.  Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.  

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. 

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 the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, 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 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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 (DHHS) grant administration regulations at 45 CFR Part 75, 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 awardees 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 award 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Retaining primary responsibility for the planning, directing, and executing the proposed research study through oversight, management, and coordination of the participating sites, personnel and outcomes. 
• Assisting the NIH Project Scientist and working with other HIPC PIs in developing the operating guidelines and consistent policies for dealing with situations that require coordinated action.
• Awardees 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 DHHS, 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 will support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PD(s)/PI(s).
• Select and recruit the EAB members for the entire HIPC.
• Coordinate NIAID staff assistance, including participation in periodic on-site monitoring with respect to compliance with Federal regulations, quality control, accuracy of data recording, sample accrual, enrollment, etc.
• Facilitate collaborations with and provide access to other NIAID-supported research resources and services.
• The NIH Project Scientist will review and assist in developing the operating guidelines and consistent policies for dealing with situations that require coordinated action.
• The NIH Project Scientist will periodically review the data generated under this award.
• The NIH Project Scientist will review progress towards achieving the final set of agreed upon milestones annually.  Determinations for future year funding will be based on satisfactory annual progress reported in the RPPR and meeting annual milestones.
• 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:

• The PD(s)/PI(s) and NIH Project Scientist will update the program milestones annually, taking into consideration recommendations from the EAB.
• The NIH Project Scientist and the PD(s)/PI(s) will coordinate the scientific objectives and progress to facilitate the achievement of program goals.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 (currently 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 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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: http://grants.nih.gov/support/ (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: 301-945-7573

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

Alison Deckhut Augustine, Ph.D. - for general scientific/research questions
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3475
Email: [email protected]

Alkis Togias, M.D. - for questions related to clinical studies/trials
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3587
Email: [email protected]

Annie Mo, Ph.D. - for general scientific/research questions
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3320
Email: [email protected]

Patricia D'Souza, Ph.D. - for scientific/research questions regarding HIV studies
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3037
Email: [email protected]

Thomas Conway, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5075
Email: [email protected]

Trevor Alford
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-747-7398
Email: [email protected]

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 45 CFR Part 75.