Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Human Immunology Project Consortium (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	Reissue of RFA-AI-09-040
Related Notices	November 19, 2015 - This RFA has been reissued as RFA-AI-15-041. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number	RFA-AI-14-007
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) on the Human Immunology Project Consortium (HIPC) invites applications from single institutions, or consortia of institutions, to participate in a network of human immunology profiling research groups in the area of non-HIV infectious disease. Applications are sought that propose to study the human immune system (1) during or following infection, (2) before and after vaccination against an infectious disease, and/or (3) before and after administration of an infectious disease vaccine adjuvant that targets innate immune components. The purpose of this FOA is to capitalize on recent advances in immune profiling technologies to measure the diversity and commonalities of human immune responses under a variety of conditions using high-throughput systems biology approaches coupled with detailed clinical phenotyping in well-characterized human cohorts. The long-term goal is to develop molecular signatures that define immune response categories/fingerprints/profiles that correlate with the outcome of infection or vaccination.

Posted Date	February 3, 2014
Open Date (Earliest Submission Date)	August 18, 2014
Letter of Intent Due Date(s)	August 18, 2014
Application Due Date(s)	September 18, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	January 2015
Advisory Council Review	May 2015
Earliest Start Date	July 2015
Expiration Date	September 19, 2014
Due Dates for E.O. 12372	Not Applicable

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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) on the Human Immunology Project Consortium (HIPC) invites applications from single institutions, or consortia of institutions, to participate in a network of human immunology profiling research groups in the area of non-HIV infectious disease. Applications are sought that propose to study the human immune system (1) during or following infection, (2) before and after vaccination against an infectious disease, and/or (3) before and after administration of an infectious disease vaccine adjuvant that targets innate immune components. The purpose of this FOA is to capitalize on recent advances in immune profiling technologies to measure the diversity and commonalities of human immune responses under a variety of conditions using high-throughput systems biology approaches coupled with detailed clinical phenotyping in well-characterized human cohorts. The long-term goal is to develop molecular signatures that define immune response categories/fingerprints/profiles that correlate with the outcome of infection or vaccination.

The human population is diverse with respect to age, ethnicity, gender, sub-clinical disease, genetic pre-disposition to disease, medication use, environmental exposures, and nutritional status. Each of these factors is known to influence the activation and regulation of the immune system, and it is important to establish baseline immune profiles in different subpopulations. However, it is not the goal of this FOA to simply describe baseline profiles. Rather, the goals are: to determine how these profiles are perturbed and eventually returned to a new homeostatic state after antigenic challenge; to rapidly disseminate these data, results, and analyses to the broader scientific community as a foundation for further study; and to integrate these findings with other studies on human immune profiling.

The NIAID is strongly committed to building a comprehensive understanding of the human immune system as it responds to infection, vaccination, and other antigenic challenges. One approach to building a deeper understanding of human immune 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 will provide insights into how the system functions as a whole. Systems data may be generated from omics technology platforms such as genomics, epigenomics, transcriptomics, RNAi screens, proteomics, metabolomics, lipidomics, and glycomics 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 and biostatistics to improve data management and analytical capabilities that will allow even richer mining of the data generated in such studies. The results of systems immunology studies will 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. Ultimately, this foundation of knowledge can also be applied to human immune-mediated diseases such as allergy, asthma, transplant rejection, autoimmune syndromes, and other inflammatory diseases.

Several studies have described human immune gene expression profiles in blood that are characteristic of certain infections and can distinguish respiratory infections of different etiologies, such as influenza A virus, Escherichia coli, Staphylococcus aureus, and Streptococcus pneumonia, which are among the most common infections leading to hospitalization of children. Signatures for several other infections have also been described, including Plasmodium, respiratory syncytial virus, dengue virus, adenovirus, Salmonella, Mycobacterium tuberculosis, and Burkholderia pseudomallei. Recent work demonstrated an association of the interferon pathway with acute viral infection, and association of the integrin pathway with acute bacterial infection. Furthermore, symptomatic versus non-symptomatic children infected with the same virus could be distinguished by transcriptional profiles. These types of results may help develop diagnostic tools that are especially needed in the acute infection setting, when effective treatments depend on rapid identification of the infectious agent; and may also define immune profiles correlated with outcomes of infection, that might assist in treatment decisions on an individual basis.

A number of studies have also used systems immunology approaches to characterize human immune signatures of different vaccines. One of the most successful vaccines in human use, the live attenuated yellow fever vaccine, is known to confer long-lasting protection after a single immunization, yet we still lack a detailed understanding of the relevant immune parameters induced by vaccination that might predict a protective response. Recently, immune profiles of response were described that correlated with, and could predict, the immunogenicity of the yellow fever vaccine in humans. Similarly, signatures of early response to influenza vaccination were described that correlated with, and could predict, influenza specific antibody titers. Importantly, signatures of the yellow fever and influenza vaccines differ in many respects, providing valuable information regarding immunological mechanisms as well as diagnostic potential.

In addition to immune parameters already implicated in innate or adaptive immunity, components from other cellular pathways were found associated with vaccine immunogenicity in profiling studies, indicating that the systems approach is likely to reveal novel interactions between the immune system and other biological systems and processes. Beyond predicting immunogenicity, it should also be possible in the future to correlate immune profiles determined before or soon after vaccination with the protective efficacy of a vaccine, and also correlate profiles with adverse events triggered by vaccination, thus providing important new tools for vaccine development. Furthermore, matching baseline or early response profiles to outcomes may distinguish individuals that would not respond well to vaccination from those that would benefit.

Although a few new adjuvants have been licensed in human vaccines in the past decade, the number of available adjuvants is still small, and progress on adjuvant development remains slow. For the purpose of this FOA, adjuvants are defined as compounds that enhance immune responses to vaccines by targeting innate immune receptors. Adjuvants may contribute significantly to vaccine reactogenicity, and it is important to study the potentially adverse as well as enhancing effects of different adjuvants during development of more effective vaccines. It is likely that the use of immune profiling approaches will help in the more rapid evaluation of adjuvant candidates as well as evaluation of different formulations and administration regimens.

The prior funding period of this program supported several research groups to conduct comprehensive systems immunology studies of human infection and vaccination (http://www.immuneprofiling.org). In addition, a prototype HIPC web portal and analysis resource (ImmuneSpace) is being developed for use by the broader research community, to serve as a centralized resource for public access to the data, and to display the immune profiles and analyses generated by the HIPC network and others. Further development of this resource will be supported through a separate funding mechanism, in parallel with this HIPC U19 research initiative. ImmuneSpace is being built in conjunction with the NIAID ImmPort database (https://immport.niaid.nih.gov), an integrated data warehouse that will serve to house HIPC-generated data and facilitate public access through ImmuneSpace.

This initiative seeks immune profiling projects that are focused on the analysis of well-defined human cohorts, and that utilize a variety of modern analytical tools appropriate for systems biology studies, to address issues of immunity in the context of non-HIV infectious disease. Investigators will use new and established comprehensive laboratory and bioinformatics technologies to generate molecular response profiles from primary immune cells and their products obtained from human volunteers within well-characterized cohorts. Each award will support the collection, storage, and characterization of human samples; and each awardee will work together with other HIPC awardees to build centralized resources such as common data standards and validated assays for use by all network investigators, and will contribute to the rapid dissemination of human immune profiling data to the wider scientific community through a publicly accessible web portal.

To promote rapid public access to HIPC-supported data and results, all HIPC Program Directors (PDs)/Principal Investigators (PIs) funded under this initiative will work closely with ImmPort and ImmuneSpace staff with regard to data submission and development of new systems for data integration, analysis, presentation, and visualization. All HIPC investigators will be expected to share their HIPC-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID. The privacy of participants will be safeguarded and confidential and proprietary information will be protected. After award and prior to data collection, data set definitions and schedules for data sharing will be negotiated with NIAID, as will plans for other resource sharing. If further schedule changes are needed throughout the funding period, they will be negotiated with NIAID after evaluation by the Steering Committee.

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.

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

• Measurement of dynamic changes in immune profiles following vaccination or infection that correlate with clinical outcome
• Comparison of longitudinal immune profiles among ethnically diverse or special populations (e.g., infants, neonates, elderly, allergic individuals, transplant recipients, patients with autoimmune disease) after infection, vaccination, or adjuvant treatment
• Identification of immune profiles that correlate with vaccine efficacy or surrogates of efficacy
• Comparison of immune profiles in vaccinated populations to populations with naturally acquired infections
• Identification of markers of mucosal or skin immune responses that contrast with markers of systemic response
• Identification of immune profiles that correlate with adjuvant function or antigen/adjuvant formulation, administration regimen, and/or route of delivery
• If practical, dissociation of markers of protective immunity from markers of vaccine toxicity/reactogenicity
• Immune responses to non-influenza pathogens (note below that only one influenza-based research project is allowed)

In addition to the required focus on the generation and analysis of human immune profiles in response to infection, vaccination, or adjuvants, each proposed project may also include:

• Development of novel bioinformatics or biostatistical tools to manage, analyze, and visualize large data sets resulting from human systems immunology studies
• Development of novel assays to define human immunological profiles or functions, including assays that minimize the sample sizes needed for immunological assays (sample-sparing assays)

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

• More than one research project that includes study of immune responses to influenza vaccination or infection
• Clinical trials clinical trials may not be proposed within the application (see Section IV. Application and Submission Information 2. Content and Form of Application Submission for clinical trial definition)
• Any animal studies, including studies that use animal models of human diseases and studies that employ humanized mice
• Systems biology studies of a microbiome(s) in the absence of systems biology studies of human immune tissues, cells, or molecules
• HIV/AIDS and related studies
• Vaccine development, adjuvant discovery/development, new vaccine formulations, and vaccine/adjuvant safety and efficacy testing
• Epidemiology studies
• Studies using only transformed human cell lines
• Genome wide association studies (GWAS)
• Studies on components of vectors that mediate infectious disease (e.g., mosquito, sand fly, tick saliva)
• Studies on infectious agents used as therapeutics, such as viral vectors for antibody delivery
• Projects predominantly focused on populations with diseases or underlying conditions unrelated to those within the scope of the NIAID mission (see http://www.niaid.nih.gov/about/whoweare/Pages/default.aspx for definition of the NIAID mission)
• Projects that do not include an assessment of human immune profiles in the context of human infectious disease, measured in primary human immune cells or tissues in response to vaccination, naturally acquired infection, or treatment with adjuvants that target innate immune receptors.

Each HIPC application must include a minimum of 2 and a maximum of 4 multi-disciplinary, synergistic research projects organized around a central scientific theme related to human immunology profiling. Each HIPC application will include an Administrative Core, a Data Management Core, and an Infrastructure and Opportunities Fund Management Core. In addition, one or more Service Cores may be proposed, but each Service Core must be used by at least two research projects.

Administrative Core

The Administrative Core will support the coordination of efforts across the component research projects and cores, and will support 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 group, as well as protection of intellectual property, regulatory compliance, 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 with other HIPC network PDs/PIs and institutions as well as within the individual group to promote synergistic research efforts. The PD(s)/PI(s) may establish an External Scientific Advisory Group (ESAG) after award that may be supported by the Administrative Core. A Steering Committee will be established to serve as the governing board of the HIPC collaborative research program.

Data Management 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. In addition, this core may include study design and statistical support for the researchers within the center.

Infrastructure and Opportunities Fund Management Core

An Infrastructure and Opportunities Fund (IOF) will be made available each year to support resources that provide additional assistance and/or technical expertise for projects undertaken by HIPC investigators. One institution will be chosen by NIAID after award from the successful applicants to manage the IOF for the entire consortium. This institution must agree to take responsibility for managing the IOF, including disbursement, administration, and reports. Management of the IOF will involve:

• Establishing an administrative structure to manage the IOF
• Disbursing and tracking IOF funds under the direction of the Steering Committee
• Implementing plans for interacting with the institutions that will receive IOF funds
• Establishing procedures, formats, and timelines for reporting on the status of IOF projects and expenditures to the NIAID and the HIPC Steering Committee

All projects supported by the IOF must be within the scientific scope of the investigators awards. The HIPC Steering Committee will make recommendations to the awardee of the IOF Management Core as to the goals, priorities, and evaluation criteria for the use of the IOF. These recommendations should include: the size and content of the applications; the frequency of application; the timeline from solicitation to funding; and the process to be used to evaluate the applications. Resources supported by the fund may be housed at particular HIPC centers or may be supported by subawards to other facilities. Any activities funded through the IOF must comply with NIH policies. Monitoring compliance is the responsibility of the IOF Management Core and NIAID program staff.

Service Core(s)

One or more Service Cores may be proposed, but only if the core will be used by at least two research projects. Service Cores are limited to providing standard assays, reagents, technologies, clinical services, repositories, statistical services, bioinformatics expertise, or other available services to investigators. They are intended to provide investigators within the HIPC group with resources that already exist and have already been validated and refined for use. Any proposed development of new technologies, assays, etc. must be presented within a research project.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $15.7 million in FY2015, which includes funding 4-5 awards as well as the Infrastructure and Opportunity Fund. Future year amounts may vary depending on annual appropriations.
Award Budget	Application budgets are limited to $2,120,000 direct costs per year which includes a limit on the budget for the Infrastructure and Opportunity Fund Management core of $120,000 per year.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is five years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

B. Duane Price, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Dr, Rm 3139
Bethesda, MD 20817
Telephone: 301-451-2592
Fax: 301-480-2408
Email: pricebd@niaid.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core	6 pages
Core (Use for Service, Data Management, and IOF Management Cores)	6 pages each
Project (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; 1
• Administrative Core: required; 1
• Data Management Core: required; 1
• IOF Management Core: required; 1
• Service Cores: optional, no minimum or maximum, but each Core must support at least two Projects
• Research Projects: required; 2-4

When preparing your application in ASSIST, use Component Type Overall .

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Location(s) (Overall)

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.

Research & Related Senior/Key Person Profile (Overall)

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/PI's abilities and capabilities to provide leadership, guidance and direction over the proposed project.

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.

Budget (Overall)

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.

PHS 398 Research Plan (Overall)

Specific Aims: Describe the central scientific theme of the proposed research program, and list in priority order the broad, long-range objectives and goals of the proposed overall program.

Research Strategy: This section summarizes the overall research strategy for the multi-project application and explains how the proposed program satisfies the purpose and objectives of this FOA as delineated in Section I. Applications responding to this FOA should describe the central theme of the proposed program and explain how the proposed research projects are synergistic and fit under the overarching program theme. The multi-project application should be viewed as a confederation of interrelated projects, each capable of standing on its own scientific merit, but complementary 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. Summarize the special features in the environment and/or resources that make this application strong or unique. If possible, provide evidence that the applicant and proposed collaborators have prior experience in the research areas proposed, and highlight accomplishments in the field and describe the synergy and collaborations that occurred. If there was no prior experience of collaboration among the investigators, explain why the proposed investigator collaborations will result in synergy. For renewal applications, also include in this section the progress made during the previous funding period.

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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Admin Core.

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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.

Project /Performance Site Location(s) (Administrative Core)

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.

Research & Related Senior/Key Person Profile (Administrative Core)

• 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.
• The PD/PI of the application must serve as the Leader of the Administrative Core. If multiple PD(s)/PI(s) are proposed, the PD(s)/PI(s) must select one PD/PI from amongst themselves to serve as the Administrative Core Leader.

Budget (Administrative Core)

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

The budget request for this core should include the costs for travel of any ESAG members to meet with HIPC personnel on an annual basis, and any additional meeting costs. A member of the HIPC program may NOT serve as an ESAG member for a different HIPC center. The budget request should also include travel funds for the PD(s)/PI(s) and Project and Core Leaders to participate in the semi-annual HIPC Steering Committee meetings.

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.

PHS 398 Research Plan (Administrative Core)

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

Research Strategy: Applicants should 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 committed level of effort; 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.

This Core may also support a seminar series or symposia comprised of speakers from outside institutions to present research results on the human immunology of infection, vaccination, or vaccine adjuvants.

Steering Committee. Once the HIPC grants are awarded, a Steering Committee will be established in collaboration with NIAID Program Officers to serve as the governing board of the HIPC collaborative research program. Its recommendations and actions will be determined by majority vote. Voting members will include one PD/PI from each HIPC award as well as the PD/PI of the ImmuneSpace web portal. Two NIAID project scientists will also serve as voting members. In order to maximize the utilization of awardee resources, the NIAID may redirect research activities within the individual awards based on recommendations of the Steering Committee, which will make recommendations on an ongoing basis for approval by NIAID staff. The PD(s)/PI(s) must attend two Steering Committee meetings per year to be held in the Bethesda, Maryland area, and also participate in periodic teleconferences scheduled by the HIPC Steering Committee. The responsibilities of the HIPC Steering Committee are described in more detail in Section VI.2. Cooperative Agreement Terms and Conditions of Award.

In addition, the Administrative Core may support an External Scientific Advisory Group (ESAG), to be formed after award at the discretion of the PD(s)/PI(s). The ESAG will evaluate scientific progress and provide advice to the center on an annual basis. Note that a member of the HIPC program may NOT serve as an ESAG member for a different HIPC center. Specific potential members of a proposed ESAG should NOT be named in the application and ESAG members must not be recruited or contacted prior to review and award. However, for renewal applications, any current or former ESAG member MUST be identified in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Generally, Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected, but they are not applicable for this component.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Administrative Core)

Not Applicable

PHS 398 Cumulative Inclusion Enrollment Report (Administrative Core)

Not Applicable

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Data Management Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management Core)

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.

Project /Performance Site Location(s) (Data Management Core)

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.

Research & Related Senior/Key Person Profile (Data Management Core)

• 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.
• The core must include designated personnel with the expertise to enable compliance with the data- and other resource-sharing requirements.

Budget (Data Management Core)

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

Request funds for personnel, equipment, supplies and services to support central data storage, data management, and information security services to all researchers within the applicant group; and to support the timely submission of data and data analyses to the ImmPort database. The core must include designated personnel with the expertise to enable compliance with the data- and other resource-sharing policies.

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.

PHS 398 Research Plan (Data Management Core)

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.

Research Strategy: Use this section to explain how the core will serve the proposed research projects. For example, describe core activities to support: study design; data collection, cleaning, and tracking; database infrastructure; information management and monitoring; management of complex cross-sectional or longitudinal data; data sharing; sample size and power calculations; and statistical analysis methods.

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

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All HIPC investigators will be expected to share their HIPC-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Data Management Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Data Management Core)

Not applicable

When preparing your application in ASSIST, use Component Type Core

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

SF424 (R&R) Cover (IOF Management Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (IOF Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (IOF Management Core)

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.

Project /Performance Site Location(s) (IOF Management Core)

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.

Research & Related Senior/Key Person Profile (IOF Management Core)

• 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 (IOF Management Core)

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

The budget request for this core should include the costs of administrative staff to manage the IOF and any needed supplies or services. This core budget may be modified by NIAID after award, but for purposes of the application, assume that: one full-time administrator will be needed; modest oversight effort will be needed from the PD/PI or other senior staff; and 35-40 post-award subawards will be issued by this core annually. Note that individual Subaward Budget Attachments should not be provided for these post-award subawards at the time of application.

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.

PHS 398 Research Plan (IOF Management Core)

Specific Aims: List in priority order the proposed activities and services of the IOF Management Core. Concisely and realistically describe the work to be completed to address issues of program communication and fiscal management.

Research Strategy: An IOF Management Core must be proposed. Use this section to describe how the IOF Management Core will operate to serve the HIPC network, including descriptions of: (1) an administrative structure that includes an experienced administrator; (2) methods of communication with the HIPC Steering Committee regarding the disbursement and tracking of IOF funds; and (3) methods for reporting on the status of IOF funds to NIAID. Also describe plans and procedures to ensure that all projects supported from the IOF will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in projects and appropriate ethical oversight.

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

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Generally, Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected, but they are not applicable for this component.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (IOF Management Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (IOF Management Core)

Not Applicable

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Service Cores)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Service Cores)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Service Cores)

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.

Project /Performance Site Location(s) (Service Cores)

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.

Research & Related Senior/Key Person Profile (Service Cores)

• 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 (Service Cores)

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

Applications proposing a Service Core(s) should indicate the specific research projects to be served by that core and explain why the core resources are not otherwise available. The percentage of funds that will be required to support each component research project that will utilize the core should also be presented.

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.

PHS 398 Research Plan (Service Cores)

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 relates to 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. Applications proposing a Service Core should indicate the specific research projects to be served by the core and explain why the core resources are not otherwise available.

Protection of Human Subjects: For cores proposing the use of human samples to be obtained with funds from the HIPC award, provide the information described in the SF424 (R&R) Application Guide.

When possible, it is strongly recommended that informed consent be used that allows broad use of de-identified stored samples and de-identified data for future studies, beyond the scope of the HIPC study; including genetic studies and unrestricted sharing of the samples and data for use by other researchers, subject to IRB approval.

For cores proposing the use of human samples to be obtained from independently-funded clinical trials, supporting documents should be uploaded in the Appendix as described in the instructions for the Appendix section below.

When clinical studies or trials 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 (http://www.niaid.nih.gov/labsandresources/resources/toolkit/pages/standards.aspx). An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Generally, Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected, but they are not applicable for this component.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

For cores proposing the use of human samples to be obtained from independently-funded clinical trials, the following materials should be included in the appendix:

• synopsis of the parent clinical trial protocol
• informed consent forms for the parent clinical trial
• informed consent forms for the proposed immune profile studies, if different from the parent trial
• reference to the ClinicalTrials.gov citation, if applicable
• table of events including the volume of blood, or amount of tissue, collected for the proposed immune profile studies
• memorandum of understanding from the clinical trial sponsors, IND holders, and Principal Investigators.

When samples for human immune profiling are to be collected from a clinical trial that is funded separately, a synopsis of the clinical trial protocol should be provided along with the final informed consent form(s) for the parent trial. To the extent permitted by applicable laws and regulations, NIH will treat as confidential trial information that the trial sponsor deems proprietary. 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 strongly justified.

The applicant should also provide a memorandum of understanding signed by the applicant, an appropriate representative of the applicant institution, the PD/PI of the parent clinical trial and his or her academic institution, an appropriate representative of the sponsor of the parent clinical trial and holder of the IND, if applicable and not one of the above. This memorandum will confirm agreement among the various parties and will outline their expectations of the 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) documentation of quality assurance procedures for both the parent clinical trial and the proposed profiling studies, and documentation of data and safety monitoring procedures for the parent clinical trial, especially for efficacy trials; (4) intellectual property management; and (5) publication of the proposed profiling study results.

Planned Enrollment Report (Service Cores)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Service Cores)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Project'.

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

Applications must include a minimum of 2 and may include a maximum of 4 research projects organized around a central scientific theme.

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

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.

Project /Performance Site Location(s) (Research Projects)

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.

Research & Related Senior/Key Person Profile (Research Projects)

• 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 (Research Projects)

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, applicants can include in their budgets 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.

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.

PHS 398 Research Plan (Research Projects)

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

Research Strategy: Projects must focus on human immune profiling and infection, vaccination, or vaccine adjuvant administration. Each project should address a common immunological theme such that synergy is clearly evident among all the proposed research projects. Each project must include proposed 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. Results from preliminary work should be included as part of the approach section, and must be contained within the page limits of the Research Strategy section. For renewals, also include in this section the progress made during the previous funding period.

Required Elements: Applications that do not meet these requirements will be considered non-responsive and will not be reviewed.

• Each proposed project must involve the generation of 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 treatment with an infectious disease vaccine adjuvant that targets an innate immune component. Cohorts should 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 may also 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.
• No more than one of the proposed research projects may involve the study of immune responses to influenza vaccination or infection. Clearly, influenza continues to be of great importance as a serious human disease, and influenza research continues to be of great value. Research on other human pathogens is also of importance, not only because such agents cause serious disease, but also because comparisons among immune profiles induced by a variety of antigenic sources and associated conditions contribute to defining the specificity of immune signatures and the potential mechanisms of response, protection, or reactogenicity. Therefore, no more than one of the proposed projects may study responses to influenza.
• All proposed research must use unbiased, non-hypothesis based, data-gathering, quantitative systems biology type experimental approaches, such as genomics, epigenomics, transcriptomics, RNAi screens, proteomics, metabolomics, lipidomics, or glycomics studies, to study human sample sets for correlation with outcomes of infection or vaccination; such as duration and severity of illness, antigen-specific antibody levels, or cytotoxic T cell responses. Frequent longitudinal sampling is strongly encouraged to enable the study of dynamic changes.

Recommended Elements: It is strongly recommended that applications include the following elements to enable comprehensive evaluation by the review panel:

• Strong rationale for selection of the human subject population(s) to be studied, the sample collection times, and the quantitative assays to be used.
• Clear description of the availability of study subjects, justification of the number of subjects to be studied, statement of the numbers of cells or tissue samples available for each study, and concise description of the statistical design for each study and the computational methods to be used for data analysis.
• Concise description of the data management and quality control systems and procedures to be used.
• Synopsis of the protocol(s) used in any independently-funded clinical trial(s) from which samples will be obtained for this program.

Although clinical trials will not be supported under this initiative, cohorts may be developed with individuals participating in vaccine clinical trials that are funded by independent mechanisms, or cohorts from independently-funded infection challenge trials in humans. Applications must not propose any clinical trials. Note however, that after award, IOF support may be requested by HIPC investigators for new small phase I or II clinical trials that are within the scientific scope of this initiative.

Clinical trial definition: For this FOA, a clinical trial is defined as a prospective study of human subjects designed to answer questions about the safety and effectiveness of biomedical or behavioral interventions. All clinical studies that require an Investigational New Drug (IND) application from the U. S. Food and Drug Administration (FDA) to conduct a clinical investigation WOULD be considered clinical trials. Studies using FDA approved interventions (e. g. licensed vaccines), that are prescribed for use as described in the intervention’s product label and are exempt per regulation from needing an IND for a clinical investigation, for the purposes of studying detailed immune response to that intervention, WOULD NOT be considered clinical trials. Applicants should contact the FDA directly to discuss the possible need for an IND application. If an IND waiver is obtained from the FDA, a copy of the waiver should be included in the application. NIAID reserves the right to decide whether a proposed clinical study is, or is not, a clinical trial based on the definitions and guidance provided here for purposes of determining whether the proposed study is responsive to the FOA. If there are any questions, applicants are strongly encouraged to contact one of the NIAID Scientific/Research Contact listed in Section VII. Note that after award, the HIPC Steering Committee may consider requests to use IOF funds to support small Phase I or II clinical trials (for more information see Section VI.2). Examples to further clarify the definition of a clinical trial for the purposes of this FOA are given below:

• a study of a seasonal influenza vaccine that is given at the appropriate time for seasonal influenza immunization and to approved populations, as indicated in the product label of the influenza vaccine to be used in the study, WOULD NOT be considered a clinical trial
• a study of a seasonal influenza vaccine that is given at the appropriate time for seasonal influenza immunization but is given to subjects outside of the approved indication age range (e. g. infants <6 months of age) WOULD be considered a clinical trial
• a study of a seasonal influenza vaccine that is given at the appropriate time for seasonal influenza immunization but uses a novel adjuvant WOULD be considered a clinical trial
• a study of an experimental influenza vaccine WOULD be considered a clinical trial
• a challenge study in which a live pathogen is administered to cause disease WOULD be considered a clinical trial; however, administration of a licensed, live-attenuated vaccine as indicated in the product label would not be considered a clinical trial.

Protection of Human Subjects: For projects proposing the use of human samples to be obtained with funds from the HIPC award, provide the information described in the SF424 (R&R) Application Guide.

When possible, it is strongly recommended that informed consent be used that allows broad use of de-identified stored samples and de-identified data for future studies, beyond the scope of the HIPC study; including genetic studies and unrestricted sharing of the samples and data for use by other researchers, subject to IRB approval.

For projects proposing the use of human samples to be obtained from independently-funded clinical trials, supporting documents should be uploaded in the Appendix as described in the instructions for the Appendix section below.

When clinical studies or trials 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 (http://www.niaid.nih.gov/labsandresources/resources/toolkit/pages/standards.aspx. An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

For projects proposing the use of human samples to be obtained from independently-funded clinical trials, the following materials should be included:

• synopsis of the parent clinical trial protocol
• informed consent forms for the parent clinical trial
• informed consent forms for the proposed immune profile studies, if different from the parent trial
• reference to the ClinicalTrials.gov citation, if applicable
• table of events including the volume of blood, or amount of tissue, collected for the proposed immune profile studies
• memorandum of understanding from the clinical trial sponsors, IND holders, and Principal Investigators

When samples for human immune profiling are to be collected from a clinical trial that is funded separately, a synopsis of the clinical trial protocol should be provided along with the final informed consent form(s) for the parent trial. To the extent permitted by applicable laws and regulations, NIH will treat as confidential trial information that the trial sponsor deems proprietary. 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 strongly justified.

The applicant should also provide a memorandum of understanding signed by the applicant, an appropriate representative of the applicant institution, the principal investigator of the parent clinical trial and his or her academic institution, an appropriate representative of the sponsor of the parent clinical trial and holder of the IND, if applicable and not one of the above. This memorandum will confirm agreement among the various parties and will outline their expectations of the 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) documentation of quality assurance procedures for both the parent clinical trial and the proposed profiling studies, and documentation of data and safety monitoring procedures for the parent clinical trial, especially for efficacy trials; (4) intellectual property management; and (5) publication of the proposed profiling study results.

Planned Enrollment Report (Research Projects)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Research Projects)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 3. Submission Dates and Times.

Part I. Overview Information contains information about Key Dates. 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.

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.

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

• Does the application adequately describe the scientific merit of each research project and core and the program as a whole?
• Are the overall program goals and scientific questions appropriate for the HIPC program?
• Will important scientific gains and synergy be achieved by combining the component projects and cores into a multi-project program?
• Will the scientific gains be beyond those achievable if each project were pursued independently?
• Is the program cohesive in terms of the research projects and cores fitting into a common theme?
• Does the PD/PI have sufficient time, effort, leadership ability, and scientific talent to develop a program of integrated research projects with a well-defined central research focus?
• If the program is multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the program?

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).

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? What is the likelihood that the results of the study will be translated into important new knowledge on human immune status and responses to infection, vaccination, or adjuvants?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Are the designated personnel sufficient to enable compliance with the data- and other resource-sharing policy?

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? If proposed for development, how innovative are the new assays or statistical or bioinformatics tools?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project ? 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?

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 children, justified in terms of the scientific goals and research strategy proposed?

In each Research Project, is there a predominant focus on human immune profiling using systems biology approaches in the context of infection, vaccination, or adjuvant function/toxicity? Are the human subject cohorts to be analyzed well characterized, available in sufficient numbers, and appropriate for the stated goals? Are adequate resources available to conduct the proposed studies, including a local database and bioinformatics expertise, sample repository, and statistical capability? Will data collection and analysis methods be appropriate in terms of quantitation, controls, and management? If proposed for development, are new assays or statistical or bioinformatics tools scientifically sound?

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?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved.

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?
• Are the plans for communication and collaboration with other HIPC centers adequate?

Data Management Core

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are there sufficient effort and expertise dedicated to both data management and data sharing policies?
• Is there sufficient bioinformatics infrastructure to support the proposed activities?
• If support is proposed for study design and statistical analyses, are sufficient effort and expertise included in the core?

Service Core(s)

• Is provision of the proposed core services to the Research Projects critical and justified?
• Is the relationship of the core to the central scientific theme of the overall program strong?
• Are the quality of 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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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.

Inclusion of Women, Minorities, and Children

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 children 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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

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

Revisions

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.

Infrastructure and Opportunity Fund (IOF) Management Core

• Is provision of the proposed core services to the HIPC program described in sufficient detail?
• Is sufficient justification provided for the management methods proposed?
• Are the personnel charged with managing the IOF appropriate?
• Are there adequate plans and procedures proposed by the applicant to assure compliance with relevant federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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 NIAID, 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.
• Compliance with data- and resource-sharing policies.

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.

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 grantee’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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

• Defining the details and goals of the project as a whole within the guidelines of this FOA.
• Overseeing/performing the scientific activities.
• Administratively managing the U19 grant.
• One PD/PI from each U19 award will be a voting member of the Steering Committee; will participate in all Steering Committee activities, meetings and teleconferences; and will follow the policies and procedures developed by majority vote of the Steering Committee.
• The PD/PI will accept close coordination, cooperation, and participation of NIAID staff in the scientific, technical, and administrative management of the HIPC program.
• While safeguarding the privacy of participants and protecting confidential and proprietary information, the PD/PI will be expected to make data publicly available. The timeline will be negotiated at the time of Award and included as a Term and Condition of Award. Data set definitions will be negotiated with NIAID as part of the data-sharing plan for the center.
• The PD/PI will ensure successful completion of the data- and other resource-sharing plans negotiated with NIAID. Sharing plans represent a commitment by the applicant institution (and its subcontractors, if any) to support and abide by the plan
• The PD/PI will establish procedures within the center to ensure that all members of that center, including any scientists added via IOF support, conform to the data-sharing and other resource-sharing plans. The final versions of NIAID-approved sharing plans will become a condition of the award. Note that funding beyond the first year may be subject to downward negotiation depending on the progress made in meeting negotiated milestones within the data- and other resource-sharing plans.
• Infrastructure and Opportunities Fund (IOF) management: after all grants have been awarded, one U19 awardee institution will be selected by NIAID to manage the IOF for the entire network. This institution must agree to take responsibility for managing the funds, including the disbursement, administration, and reporting on the use of such funds as recommended by the Steering Committee and approved by NIAID. Management of the IOF will involve:
  • Establishing an administrative structure to manage the IOF.
  • Disbursing and tracking IOF funds under the direction of the Steering Committee.
  • Implementing plans for interacting with the institutions that will receive IOF funds.
  • Establishing procedures, formats, and timelines for reporting on the status of IOF projects and expenditures to the NIAID and the HIPC Steering Committee.
• The PD/PI may convene an External Scientific Advisory Group (ESAG) for the individual center, to be formed after award at the discretion of the PD/PI. The ESAG would evaluate scientific progress and provide advice to the center on an annual basis.
• 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:

• Two NIH Project Scientists will have substantial programmatic involvement as described below:
  • Provide input into the design of research activities.
  • Play a key role in coordinating research efforts.
  • 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, etc.
  • Evaluate the adequacy of data-sharing and other resource-sharing plans when making funding recommendations. NIAID program staff may negotiate modifications of sharing plans with the applicant.
  • Ensure that all HIPC investigators conform to the HIPC data-sharing and other resource-sharing policies.
  • Participate in investigator and Steering Committee meetings.
  • Facilitate collaborations with and access to other NIAID-supported research resources and services.
  • Facilitate negotiations with companies interested in participating in clinical studies with HIPC investigators.
  • Advise in project management and technical performance.
  • Serve as liaison/facilitator among awardees and with the ImmPort database and ImmuneSpace.
  • Serve as a resource for scientific and policy information related to the goals of the awardees research.
  • Have confidential access to data generated under this Cooperative Agreement, for use in the preparation of internal reports on the activities of the awardees.
  • Provide oversight for human subjects protections.
  • Provide assistance to the Steering Committee in the development of procedures for evaluating the performance of research studies and monitoring any clinical trials developed via the IOF.
  • Organize the Steering Committee meetings and compile meeting minutes
  • Promote coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.
  • Provide guidance to the awardees with regard to:
    • Compliance with Federal regulations
    • Oversight and monitoring of collaborative research
    • Feasibility of timely completion
    • Plans for incorporation of new technologies or other resources
• After award of the grants, the NIAID may establish an External Advisory Board (EAB) to advise NIAID by reviewing, evaluating, and prioritizing the scientific progress of the individual awardees and the network. EAB members will be selected by NIAID and applicants should NOT contact any individuals for the purpose of serving on this EAB, nor should they identify any such individuals in their applications.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Steering Committee membership: the HIPC network will be governed by a Steering Committee to coordinate and facilitate research activities for the overall program; to ensure close coordination with the ImmPort database and ImmuneSpace; to facilitate compliance with the data- and other resource-sharing policies; and to promote optimal research flexibility, synergy, and efficiency.
• Steering Committee responsibilities will include:
  • Evaluate progress of the individual research projects and provide guidance
  • Establish protocols for the review and modification of ongoing studies, which may include recommendations for new collaborations or resource allocations among the HIPC members
  • Coordinate resource sharing among the HIPC centers
  • Assist as required in preparing formal reports summarizing activities and/or progress within the HIPC network
  • Recommend procedures to solicit and evaluate applications for HIPC IOF support which may include small phase I or II clinical trials
  • Make recommendations to support specific applications through the IOF, recommend budget allocations for each IOF project, and monitor the progress of funded projects
  • Define needs for centralized resources such as standardized assays, bioinformatics expertise, or sample repositories
  • Facilitate interactions among HIPC investigators and with the Immport and ImmuneSpace staff
  • Review schedules for submission of HIPC-generated data and data analyses from each HIPC center for public dissemination
  • Promote compliance of HIPC members with the schedules for data- and other resource-sharing
  • Define procedures for the publication and/or oral presentation of results or data collected collaboratively within the HIPC network
  • Organize and convene semi-annual face-to-face meetings to include Steering Committee members as well as other HIPC scientists and ImmPort and ImmuneSpace staff to present research progress and discuss potential collaborations between centers
  • Meet by teleconference on a periodic basis to discuss business issues and exchange scientific advances
  • All HIPC investigators will be required to accept and implement policies approved by the Steering Committee.
• The Steering Committee will include one PD/PI from each awarded U19 as a voting member, each with one vote; will include the PD/PI of ImmuneSpace as a voting member; and will include the two NIAID Project Scientists as voting members.
• Research Project and Core Leaders and other HIPC investigators may serve as non-voting members, as determined by the Steering Committee. NIAID may also appoint additional staff to serve on the Steering Committee as non-voting members.
• The Steering Committee will establish subcommittees and working groups with discrete responsibilities and authorities to promote comprehensive data reporting, uniformity of practices, assay validation and standardization, data and sample sharing, interactions with the ImmPort database and ImmuneSpace staff, and priority setting.
• The Steering Committee may recommend use of the IOF to support small Phase I or II clinical trials. The focus of this work will be limited to the overall research scope and objectives of this FOA. HIPC researchers may propose such clinical trials to the Steering Committee.
• If a clinical trial is approved by the Steering Committee and NIAID, and if the project is feasible under the fiscal constraints of the IOF, appropriate activities may be initiated to plan, conduct, and monitor the study in compliance with the NIAID Clinical Terms of Award (http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf). No clinical trials will be initiated or conducted without the full participation and approval of NIAID and completion of all required documentation outlined in the NIAID Clinical Terms of Award and other Federal regulations, guidance, and NIH policy governing the conduct of clinical trials. All clinical trials funded through the IOF will be conducted using existing NIAID or NIH clinical trial infrastructure, such as: protocol review and approval by the Clinical Research Committee of the Division of Allergy, Immunology and Transplantation (DAIT), NIAID; input from the DAIT Regulatory Group; and use of facilities funded by the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, or other facilities already established and maintained by NIH or a network-sponsoring institution, and approved by NIAID. Network resources will not be used to develop or support clinical trial infrastructure. Any proposed trials may not exceed the clinical and scientific resources of an applicant’s institution(s) and must not exceed the funding period of the network. Note that Phase III and IV clinical trials will NOT be supported by the IOF.

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 Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Helen Quill, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3514
Email: hquill@niaid.nih.gov

Alkis Togias, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3571
Email: togiasa@niaid.nih.gov

B. Duane Price, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2592
Email: pricebd@niaid.nih.gov

Roberta Dunlap Wolcott
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2685
Email: wolcottr@niaid.nih.gov

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 Parts 74 and 92.