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 infectious disease. Applications are sought that propose to study the human immune system (1) before and after vaccination against an infectious disease, including HIV; (2) before and after administration of an adjuvant that selectively targets immune components; and (3) during or following natural infection, including HIV. The purpose of this FOA is to characterize human immune responses/mechanisms triggered by vaccines, adjuvants, and naturally occurring infection by capitalizing on recent advances in immune profiling technologies. Studies supported under this FOA will 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 (1) effective responses to vaccines, (2) adjuvants or (3) the outcome of naturally-occurring infection. However, this FOA will not support examination of pathogen-specific immune responses where the primary focus of the application is for vaccine development/testing or to understand microbial pathogenesis or microbial mechanisms to evade host immunity.

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 challenge with an antigen (e.g., vaccination or natural infections) and/or adjuvant(s); 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.

An additional goal of this program is to advance research by promoting rapid public access to HIPC-supported data and results through public portals such as ImmPort and ImmuneSpace, as well as the development of new methods for data integration, analysis, presentation, and visualization to further research and development in this field.

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. NIAID’s investment in systems biology spans over a decade and includes programs to discover new immune response genes and mechanisms important for protection from infectious and immune-mediated diseases using animal models, development of computational models of immunity, and systems biology of infectious diseases (http://www.niaid.nih.gov/labsandresources/resources/bioinformatics/Pages/systemsBiology.aspx) 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, or understanding the host immune response to infectious diseases of humans.

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 pneumoniae, which are among the most common infections leading to hospitalization. Signatures for several other infections have also been described, including those due to Plasmodium spp., 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, such as with influenza A virus, 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. Although development of diagnostics is not within the scope of this FOA, these types of results may help inform future efforts to 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 individualized basis.

A number of studies have also used systems immunology approaches to characterize human immune signatures of different vaccines. Recently, immune profiles of response to the yellow fever vaccine were described that correlated with, and could predict, the immunogenicity of the 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 triggered by different types/forms of vaccines.

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. Data collected through systems immunology approaches may also provide foundational information to the broader research community to develop correlates of vaccine efficacy, as well as adverse events triggered by vaccination. Furthermore, matching baseline or early response profiles to outcomes may distinguish individuals who would not respond well to vaccination from those who would benefit.

Although a few new adjuvants have been introduced as components of recently licensed human vaccines, 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 selectively targeting innate immune receptors. Adjuvants may contribute significantly to immune-mediated host reactogenicity, and it is important to study the potentially adverse as well as enhancing effects of different adjuvants. It is likely that the use of immune profiling approaches will help in the more in-depth evaluation of adjuvant candidates and their mechanisms of action, as well as evaluation of the effects of route of adjuvant delivery on immune activation.

The prior funding periods of this program, in 2010 and 2015, have offered support to several research groups to conduct comprehensive systems immunology studies of human vaccination and infection (http://www.immuneprofiling.org). The data generated by these groups are accessible in the NIAID-supported ImmPort database. In addition, the same data will be accessible in a HIPC web portal and analysis resource (ImmuneSpace), which will be publicly available in the fall of 2015.

In the summer of 2015, three U19 cooperative agreement awards were made in response to the first renewal of the HIPC program. This initiative seeks to fund additional immune profiling projects that are focused on the analysis of well-defined and characterized human cohorts utilizing a variety of modern tools appropriate for systems biology analyses, which involve 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, and describe various aspects of host immunity in the context of vaccinations, adjuvants and/or microbial infections. 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. The new HIPC awardees will join the 2015 awardees and operate as one consortium under one Steering Committee (see below). Each award will support the collection, storage, and immunologic characterization of human samples, and each awardee will work together with other HIPC awardees to further build and utilize existing centralized resources such as common data standards and validated assays for use by all network investigators.

Since the prior and current HIPC projects included a substantial amount of work on dengue and influenza, no more than one of the proposed projects may study responses to influenza or dengue. Applicants may include one project that studies responses to influenza and one project that studies responses to dengue, if appropriate for their program goals. Clearly, influenza and dengue continue to be of great importance as serious human diseases, and research on influenza or dengue continues to be of great value. However, 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.

This initiative will support immune profiling of individuals receiveing licensed vaccines or naturally exposed/infected with pathogenic organisms, as well as individuals participating in vaccine clinical trials that are funded by other mechanisms or independently-funded infection challenge studies. In addition, clinical trials using U. S. Food and Drug Administration (FDA) approved interventions (e. g. licensed vaccines) that are prescribed for use per indication (as described in the intervention’s product label) and are exempt by regulatory authorities from needing an Investigational New Drug (IND) application can be supported by this FOA. Applicants should directly contact the FDA or the equivalent non-US regulatory authority (if applicable) to discuss whether an IND (or equivalent) application is required and obtain a waiver, if not. NIAID reserves the right to decide whether a proposed clinical trial is responsive to the FOA based on the definitions and guidance provided herein. To clarify any clinical trial related matter, applicants are strongly encouraged to contact one of the NIAID Scientific/Research Contact(s) listed in Section VII.

Each award will contribute to the rapid dissemination of human immune profiling data to the wider scientific community through ImmPort and ImmuneSpace. Since the multi-project U19 cooperative agreement mechanism is being used, each application is expected to be synergistic. For the purpose of this FOA, synergy will be assessed by the creation of a whole that is greater than the sum of its parts in terms of advancing our understanding of the human immune response to vaccines, adjuvants, and/or natural infection. For example, a synergistic application may use different infections, vaccines or adjuvants as immune triggers to examine common hypotheses or employ common analysis methods to identify shared or unique mechanisms of immune-mediated protection or pathogenesis.

To promote rapid public access to HIPC-supported data and results, all HIPC Program Directors /Principal Investigators (PDs/PIs) funded under this initiative will work closely with ImmPort and the ImmuneSpace staff for 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, consistent with achieving the goals of the program. Privacy of participants will be safeguarded and confidential and proprietary information will be protected. Prior to award and data collection, data set definitions and schedules for data sharing will be negotiated with NIAID as appropriate, 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 HIPC Steering Committee.

It is expected that all HIPC-supported data submitted to ImmPort or other public portals will be released within 9 months to 1 year of submission or upon publication, whichever comes first.

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

Steering Committee

To promote scientific collaboration, exchange of scientific findings among HIPC centers, and coordination of data dissemination to the broader scientific community, a Steering Committee will be established and serve as the governing board of the HIPC collaborative research program. Additional functions of the Steering Committee will include managing a HIPC Infrastructure and Opportunities Fund (IOF) and recommending to NIAID redirection of research activities within individual HIPC awards in order to maximize the utilization of awardee resources. The HIPC IOF Management Core has been awarded and will support IOF projects, including infrastructure, pilot projects, or small clinical trials, for the current HIPC awardees and additional HIPC projects awarded in response to this FOA. This Core will manage distribution of funds to projects awarded by the IOF. Each HIPC center will be represented by one PD/PI as a voting member of the Steering Committee. In addition, NIAID Project Scientists and the Director of ImmuneSpace will be non-voting members.

External Advisory Board (EAB)

An EAB will be convened by NIAID to advise NIAID by reviewing, evaluating, and prioritizing the scientific progress of the individual HIPC awardees and the Consortium as a whole. EAB members will be selected by NIAID after award and should not be proposed by applicants.

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

• Measurement of dynamic changes in immune profiles following vaccination, adjuvant administration or natural infection that correlate with clinical outcome, including examination of differential responses in males versus females.
• Comparison of longitudinal immune profiles among ethnically diverse or special populations (e.g., infants, neonates, elderly, atopic individuals, transplant recipients, patients with autoimmune disease) after administration of a vaccine or adjuvant, including examination of differential responses in males versus females.
• Identification of immune profiles that correlate with vaccine efficacy or surrogates of efficacy.
• Comparison of immune profiles in vaccinated populations to immune profiles in populations with naturally acquired infections.
• Identification of markers of mucosal or skin immune responses that reflect or 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. However, applications that focus on vaccine development are not within the scope of this FOA.
• Dissociation of markers of protective immunity from markers of vaccine toxicity/reactogenicity.
• Immune responses to non-influenza, non-dengue pathogens (note below that only one influenza- and/or one dengue-based research project per HIPC application is allowed, since immune profiling studies using these pathogens was covered extensively by the 2010 and 2015 HIPC awardees.).

HIV-focused applications: Immune profiling applications that focus entirely on HIV immunogens (i.e., HIV infections or individuals receiving HIV vaccines/adjuvants), or alternatively also include studies with non-HIV immunogens specifically to gain comparative information to facilitate future HIV vaccination strategies. The key requirement for HIV applications should be a coherent set of interrelated research aims with a clear overall focus on the use of immune profiling to advance research progress toward an effective HIV vaccine. In that context it would be acceptable to propose work with non-HIV immunogens to address specific knowledge gaps about HIV vaccine design by obtaining comparative information from immune responses to HIV and non-HIV immunogens

Examples of specific research areas of interest to HIV-focused applications include:

• Measurement of dynamic changes in immune profiles following vaccination, adjuvant
• administration, or natural infection that correlate with clinical outcome.
• Comparison of longitudinal immune profiles among ethnically diverse or special populations (e.g., infants, neonates, elderly, atopic individuals, transplant recipients, patients with autoimmune disease) after administration of a vaccine or adjuvant.
• Measure dynamic changes in immune profiles following natural coinfection or superinfection with two or more distinct HIV viruses that correlate with favorable immunological and/or clinical outcome.
• Studies of immune responses to unlicensed HIV vaccine candidates (where the clinical trial is supported and conducted by sources outside HIPC). Examples of specific areas of HIV vaccine research interest include:
  • systems serology of responses to HIV vaccines;
  • examination of the developing role of Fc receptors in HIV vaccine antibody responses,;
  • development and roles of potentially protective non-neutralizing antibody responses to HIV vaccines;
  • determinants of vaccine response durability;
  • examinations of adjuvant-driven affinity maturation of Ab responses to HIV vaccination;
  • Determination of the role of baseline inflammation in shaping HIV-vaccine induced innate and adaptive immunity; exploring pre-vaccination interventions, such as Probiotics or anti-inflammatory drugs, to steer immune responses to yield effective protection; and
  • comparisons of HIV-vaccine induced immunity in different genders, populations of varying body mass index (BMI) in resource-limited and resource-rich populations.

All proposed research must include unbiased, 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 (e.g. duration and severity of illness, antigen-specific antibody levels, or cytotoxic T cell responses, etc). Frequent longitudinal sampling is strongly encouraged to enable the study of dynamic changes.

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

• Development of novel bioinformatics, computational modeling 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).

Each proposed project must generate human immune response profiles using primary human immune cells or tissues obtained (1) during or after infection, (2) before and after vaccination against an infectious disease (s), and/or (3) before and after administration of an adjuvant that targets an immune component. Cohorts must be developed with individuals receiving licensed vaccines according to label, or receiving standard clinical care for infection. Alternatively, samples may be used from cohorts participating in independently-funded clinical trials of vaccination or infection. A project 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. Applications that do not meet these requirements will be considered non-responsive and will not be reviewed.

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.
• More than one research project that includes study of immune responses to dengue vaccination or infection.
• Clinical trials requiring a regulatory application (e.g., IND from the US FDA or other equivalent non-US regulatory authority). This definition includes studies that utilize experimental exposures to infectious agents.
• Any animal studies, including studies that use animal models of human diseases or studies that employ humanized mice.
• Systems biology studies of a microbiome(s) in the absence of systems biology/profiling studies of human immune tissues, cells, or molecules.
• Epidemiology studies.
• Studies using only transformed human cell lines.
• Genome wide association studies (GWAS).
• Studies on components of arthropod vectors that transmit infectious disease (e.g., mosquito, sand fly, tick saliva).
• Studies on infectious agents used as therapeutics, such as viral vectors for antibody delivery.
• Examination of pathogen-specific immune responses where the primary focus of the application is for vaccine development or testing of novel vaccine candidates or to understand microbial pathogenesis or microbial mechanisms to evade host immunity.
• Projects predominantly focused on populations with diseases or underlying conditions unrelated to those within the scope of the NIAID mission.
• Projects that do not include an assessment of human immune profiles in the context of human immunologic or infectious disease, measured in primary human immune cells or tissues in response to vaccination, naturally acquired infection, or treatment with adjuvants that target innate immune receptors.

Each HIPC application must include: Research Projects, an Administrative Core, a Data and Analysis Core, and a Clinical Core. Service Cores are optional.

Research Projects

Research Projects will be multi-disciplinary, synergistic projects organized around a central scientific theme focused on human immunology profiling.

No more than one of the proposed research projects within an application may examine immune responses to influenza or dengue vaccination or infection. Therefore, applicants may include one project that studies responses to influenza and one project that studies responses to dengue, if appropriate for their program goals.

Administrative Core

The Administrative Core will support the coordination of efforts across the component research projects and cores, and activities to advance integration into the broader HIPC network. This core will be responsible for organization, management, decision-making, and periodic evaluations within the individual HIPC group, 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. 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.

Data Management and Analysis Core

This core will provide central data storage, data management and information security services to all researchers within the center, and will be responsible for ensuring the timely submission of data and data analyses obtained under this award to the ImmPort/ImmuneSpace databases. In addition, this core will provide bioinformatics expertise and data integration and analysis support, including computational modeling if necessary for the application. The core may also include study design and statistical support/services for the researchers within the center. The Core Leader, or their designate, of the Data Management and Analysis Core will represent the HIPC center in a HIPC Data Management and Integration Sub-Committee that will operate under the Steering Committee to promote cross-HIPC collaboration including data sharing, refinement of data standards, and data analysis and integration methods.

Clinical Core

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

Service Core(s)

These Cores are limited to providing standard assays, reagents, technologies, repositories, or other available services to investigators. They are intended to provide investigators within the HIPC group with resources and services that already exist and are well characterized for use by at least two projects. Service Cores will not propose the development of new technologies.

For additional information about the Human Immunology Project Consortium and this FOA, see "Questions and Answers for RFA-AI-15-041" at http://www.niaid.nih.gov/researchfunding/qa/Pages/RFA-AI-15-041.aspx#

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

An individual can be PD/PI on only one application.

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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, including Supplemental Grant Application Instructions 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:

Paul Amstad, Ph.D.
Telephone: 240-669-5067
Fax: 301-480-2408
Email:pamstad@niaid.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (Use for Administrative Core)	6 pages
Core (Use for Data Management and Analysis Core, Clinical Core, Service Core(s))	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 and Analysis Core: required,1
• Clinical Core: required, 1
• Service Core: optional, up to 3, but each core must support at least 2 Projects
• Research Projects: required, minimum 2, maximum 3

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.

Complete entire form.

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

Follow standard instructions.

Facilities and Other Resources: Summarize the special features in the environment and/or resources that make this application strong or unique

Enter primary site only.

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

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

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

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

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

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

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

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: Summarize the overall research strategy for the multi-project application and explain how the proposed program satisfies the purpose and objectives of this FOA. 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. Highlight the overall synergy across the proposed projects and cores to advance our understanding of human immune responses to infection, vaccination or adjuvants.

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

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

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

Request funds to support the travel of the PD(s)/PI(s) to attend the annual face-to-face meetings to be held in the Bethesda, MD area and organized by the NIAID Project Scientists (2 full days per meeting).

Request funds for the PD(s)/PI(s) and relevant staff to participate in periodic Steering Committee teleconferences scheduled by the NIAID Project Scientists.

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.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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

Research Strategy: Provide a staffing and administrative plan that includes a discussion of the structure and roles of administrative and scientific staff for the core, including: the 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.

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

Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

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.

Not Applicable

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 and Analysis 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 and Analysis Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Analysis 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. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

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

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

Request funds 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/ImmuneSpace database.

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

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

PHS 398 Research Plan (Data Management and Analysis Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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: Explain how the core will serve the proposed research projects. For example, describe core activities to support: statistical consideration of study design; data collection, cleaning, and tracking; database infrastructure; information management and monitoring; management of complex cross-sectional or longitudinal data; computational modeling (as needed); data sharing, as appropriate; sample size and power calculations; and statistical analysis and data integration methods.

In regards to Sample Size justifications for activities related to data analysis/integration:

Describe principles and methods that the Core will utilize in providing support to the individual research projects so that sample sizes are sufficient to provide meaningful information information in terms of data analysis and/or data integration across the program. If primary study results will be descriptive in nature, the methods that are used should ensure sufficient precision in the proposed estimates. If primary hypotheses are being formally tested, applicants must demonstrate sufficient statistical power to elucidate key differences that support these primary hypotheses. In many settings, it will be appropriate to justify the sample size both with respect to analysis/integration of data for hypothesis testing and in descriptive studies.

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

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All HIPC- investigators, including any scientists added via IOF support, will be expected to share their HIPC-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID. The Data Sharing plans should describe the procedures to be used within the center to achieve this goal as appropriate.

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 and Analysis Core)

Not Applicable

PHS 398 Cumulative Inclusion Enrollment Report (Data Management and Analysis 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 (Clinical 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 (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical 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. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Other Attachments: If the Clinical Core supports projects proposing the use of human samples to be obtained from independently-funded clinical trials, the following materials MUST be included;

Applications lacking these materials will be considered incomplete and will not be reviewed.

• 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 sponsor(s), IND holder(s), and Principal Investigator(s).

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

If the information provided about a clinical trial, as described above, contains proprietary information of commercial value, applicants are strongly advised to follow all applicable instructions for proprietary information in the SF424 application.

The memorandum of understanding 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.

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

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

Request funds to support all functions of this core including clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the HIPC center will conduct, development of protocol-specific case report forms, training of clinical personnel prior to protocol initiation (both cGCP and protocol-specific training), monitoring of the clinical component of the study, capturing and reporting adverse events related to any intervention or procedure, handling protocol deviations, supporting the Data Management and Analysis Core in clinical data cleaning.

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

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

PHS 398 Research Plan (Clinical Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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

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

Include a table summarizing the clinical samples/cohorts to be used in the entire program. The table should include: a short description of each cohort; the criteria/justification for selecting the cohort; the number, age range, and gender composition (percentage) of subjects included in each cohort; the sample source: independently-funded clinical trial or other study, recruited for a HIPC study; the status of the sample/cohort: to be collected, completed, ongoing etc; and for samples from independently funded clinical trials, the Clinical Trials.gov registration number.

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

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

• Generally, Resource Sharing Plans 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 (Clinical 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 (Clinical Core)

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 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 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 (Service Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Service 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. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

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

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

Request the percentage of funds that will be required to support each research project that will utilize the core.

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

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

PHS 398 Research Plan (Service Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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. Indicate the specific research projects to be served by the core and explain why the core resources are not otherwise available. Any proposed development of new technologies, assays, etc. must be presented within a research project and not in a service core.

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

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

• Generally, Resource Sharing Plans 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 (Service Core)

Unless the Core will be receiving and storing human samples from independently-funded clinical trials or studies, do not provide a Planned Enrollment form under this Core. Refer to each Research Project where those forms should be included.

PHS 398 Cumulative Inclusion Enrollment Report (Service Core)

Unless the Core will be receiving and storing human samples from independently-funded clinical trials or studies, do not provide a Cumulative Inclusion Enrollment form under this Core. Refer to each Research Project where those forms should be included.

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.

SF424 (R&R) Cover (Research Project)

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 Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

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

Other Attachments: For studies proposing to use samples from clinical trials of U.S. Food and Drug Administration (FDA) approved interventions (e.g., licensed vaccines) that are exempt by regulatory authorities from needing an IND, a copy of the IND waiver obtained by the FDA or the equivalent non-US regulatory authority should be included.

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

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 Project)

• 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 Project)

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, include 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.

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

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

PHS 398 Research Plan (Research Project)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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

Research Strategy: A project must focus on human immune profiling and infection, vaccination, or vaccine adjuvant administration in well-characterized populations. Each project should address a common immunological theme such that synergy is clearly evident among all the proposed research projects. Each project must propose studies with primary human immune cells or tissues. Describe how the proposed research will contribute to meeting the program’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project’s relevance to the primary theme of the application and how it will synergize with the other projects and cores. Include results from preliminary work.

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

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

• All applications must describe the unbiased, data-gathering, quantitative systems biology type experimental approaches used to study human sample sets for correlation with outcomes of infection or vaccination (e.g., duration and severity of illness, antigen-specific antibody levels, or cytotoxic T cell responses, etc.).

Recommended Elements: It is strongly recommended that applications include the following elements:

• 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, statistical justification of the number of subjects to be studied (see below), statement of the numbers of cells or tissue samples available for each study, and concise description of the design of each study and the computational methods and statistical approaches 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, without duplicating the synopsis of the parent clinical trial protocol submitted in the Clinical Core.
• Sample size calculations: Provide justification for the planned sample size to illustrate that it is sufficient to provide meaningful information regarding immune responses to infections or vaccines. If the primary study results will be descriptive in nature, this justification would entail ensuring there is sufficient precision in these estimates. If a primary hypothesis is being formally tested, applicants must demonstrate sufficient statistical power to detect key differences that support the primary hypothesis. In many settings, it will be appropriate to justify the sample size both with respect to hypothesis testing and in descriptive studies.
• For studies where the primary study outcomes are descriptive in nature (such as estimation of immune response to a vaccine or natural infection): Expected confidence interval widths should be given. These confidence interval widths ideally should be based on previous data, which must be cited. If such data are not available, a table should be presented with confidence interval width as a function of a range of plausible data characteristics (such as standard deviation). The confidence interval width should reflect a reasonable level of accuracy of the estimate.
• For studies where hypothesis testing is planned (such as testing for association between potential biomarkers and post-vaccine immune markers): Power calculations should be provided for the primary hypothesis test(s). These calculations ideally would be based on cited historic data. When no such data are available, a table of powers across a plausible range of data characteristics (such as effect size and standard deviation) should be presented. Typically, power calculations should suggest that the planned sample size will yield at least 80% power to detect the relevant effect size at the specified alpha level.

Protection of Human Subjects: 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 or other studies, supporting documents should be uploaded in the Appendix.

When clinical studies are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study (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 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, including any scientists added via IOF support, will be expected to share their HIPC-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID. The Data Sharing plans should describe the procedures to be used within the center to achieve this goal as appropriate.

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 (Research Project)

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 Project)

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. 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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

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

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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 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.

• Are the proposed projects and cores scientifically compelling?
• 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?
• If applicable, was the progress made in the last HIPC funding period satisfactory?

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, and/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, and/or use of adjuvants? Are the human subject cohorts to be analyzed well characterized, available in sufficient numbers, and appropriate for the stated goals? Are adequate approaches proposed to conduct the studies, including availability of 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? For HIV-focused applications that include non-HIV immunogens (i.e., components, vaccines and/or infections): does the applicant adequately address how these non-HIV immunogens will provide comparative information to facilitates HIV vaccination strategies?

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 and Analysis Core

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are sufficient effort and expertise dedicated to data management, data analysis, integration and sharing methods?
• Is there sufficient bioinformatics infrastructure to support the proposed activities?
• If support is proposed for study design, statistical analyses and computational modeling (if applicable), are sufficient effort and expertise included in the core?

Clinical Core

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are the staffing and administrative plan appropriate to facilitate attainment of the objectives of the proposed core?
• Are the described processes and procedures to provide a uniform screening and characterization of potential participants in the studies proposed by the center’s research projects appropriate and adequate?
• Are the described processes and procedures for clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the HIPC center will conduct, development of protocol-specific case report forms, training of clinical personnel prior to protocol initiation, preparing IRB applications and other approval processes, preparing annual progress reports to the IRB and NIH, monitoring of the clinical component of the study, capturing and reporting adverse events related to any intervention or procedure, handling protocol deviations, and supporting the Data Management and Analysis Core in clinical data cleaning appropriate and adequate?

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

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

When the proposed project or core 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.

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.

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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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

Not Applicable

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

Not Applicable

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

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

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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 share all HIPC-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID. Data submission and release plans will be negotiated prior to award. 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.
• All HIPC investigators will be required to accept and implement policies approved by the Steering Committee.
• 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:

• NIH Project Scientists will have substantial programmatic involvement as described below:
• Provide input into the design of research activities.
• 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 require 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 HIPC web portal, 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 and provide monitoring for any studies that involve more than minimal risk for participants or that involve vulnerable populations.
• 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.
• Promote coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.
• Provide advice to the awardees with regard to:
• 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 will 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 as to re-direction, if needed
  • 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
• The Steering Committee will include one PD/PI from each awarded U19 as a voting member, each with one vote; will include the Director of ImmuneSpace as a non-voting member; and will include the NIAID Project Scientists as non-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 NIAID Clinical Research Committees, and by an NIAID Data and Safety Monitoring Board; input from NIAID Regulatory Groups; 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 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 Research Performance Progress Report (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)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Alison Deckhut Augustine, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3475
Email: augustine@niaid.nih.gov

Alkis Togias, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-8973
Email: togiasa@niaid.nih.gov

B. Fenton Hall, M.D., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-2544
Email: lhall@niaid.nih.gov

Kevin W. Ryan, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-3758
Email: kr90p@nih.gov

Paul Amstad, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5067
Email: pamstad@niaid.nih.gov

Roberta Dunlap Wolcott
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2964
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 Part 75.