Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Cooperative Centers on Human Immunology (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	Reissue of RFA-AI-08-014
Related Notices	December 4, 2017 - This RFA has been reissued as RFA-AI-17-040.
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-016
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	The purpose of this Funding Opportunity is to support hypothesis-testing, mechanistic studies on the activation and regulation of human immune responses in the context of infectious disease. The immediate objectives are to support research on human immunological responses to infection, vaccination against infectious disease, or administration of a vaccine adjuvant(s) that targets an innate immune receptor(s); and to support the stable, flexible, centralized infrastructure needed to promote and coordinate multi-disciplinary research in human immunology as it relates to defense against infectious disease. This research program was initiated by NIAID in fiscal year 2003 and is being renewed for the second time through open competition. All qualified investigators are invited to apply; prior funding under this program or through NIAID or NIH is not required.

Posted Date	March 21, 2013
Letter of Intent Due Date(s)	June 28, 2013
Application Due Date(s)	July 29, 2013
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	November, 2013
Advisory Council Review	January, 2014
Earliest Start Date	May, 2014
Expiration Date	July 30, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of 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

The long-term goal of the Cooperative Centers on Human Immunology (CCHI) program is the translation of immunology research into clinical applications in humans in the area of infectious disease. The immediate objectives are to support research on the molecular mechanisms by which the human immune system is activated and regulated in response to infection, vaccination against infectious disease, or administration of a vaccine adjuvant(s) that targets an innate immune receptor(s); and to support the stable, flexible, centralized infrastructure needed to promote and coordinate multi-disciplinary research in human immunology as it relates to defense against infectious disease.

The definitive study of immune response and regulation is more difficult to achieve in humans than in animal model systems. However, results from animal studies do not always translate faithfully to humans, and research must be conducted with human samples, to verify findings from animal systems or to discover and characterize the most relevant human pathways. Not only are experimental approaches more limited in humans, but genetic and environmental heterogeneity make it more difficult to draw definitive conclusions. In addition, there is an ongoing need to develop new technologies that will facilitate studies in humans; for example, by minimizing sample sizes needed to obtain information, by allowing measurements of new parameters from readily obtained samples, or by imaging immune activity in situ utilizing a variety of approaches.

Immune-based defenses constitute very powerful weapons that complement drug-based approaches to combat infectious disease. The development of safe and effective vaccines will depend on better understanding of systemic and localized immune capacity, and of variability among human populations at both the innate and adaptive levels of immunity and immunoregulation. Molecular mechanisms responsible for potent short-term immunity and for long-term immune memory must be understood and optimized for new applications. Immune-based reagents, such as antibodies or anti-microbial peptides, are needed for the passive protection of at-risk populations, and novel immune targets should be defined and tested to enhance immunoregulatory strategies.

The CCHI program was initiated by NIAID in fiscal year 2003 and is being renewed for the second time through open competition. This research program addresses recommendations from several expert panels convened to identify research needs in the area of biodefense, as well as the NIAID Strategic Plan on Biodefense (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Pages/strategicplan.aspx). Thus, renewal of this program is part of NIAID's commitment to the overall biodefense effort, through continuing support for cooperative immunology centers focused on the advancement of research to understand how the human immune system functions and how it may be targeted to protect against infectious disease. Multi-investigator teams will be supported to conduct highly synergistic research with a scope of activities not possible with other funding mechanisms.

The program will be milestone-based. After award, specific research milestones and timelines for each Research and Technology Development Project will be defined by the Program Director/Principal Investigator (PD/PI) working together with the assigned NIAID Program Officer, and funding beyond the first year will be contingent upon satisfactory progress in meeting negotiated milestones.

All qualified investigators are invited to apply; prior funding under this program or through NIAID or NIH is not required.

The CCHI program renewal includes some modifications from prior funding periods. It will be non-overlapping and complementary to the NIAID Human Immunology Project Consortium program that was established in 2010 (www.immuneprofiling.org), and also complementary to ongoing NIAID research programs dedicated to T cell and antibody epitope discovery (Large Scale T Cell Epitope Discovery; B Cell Epitope Discovery and Mechanisms of Antibody Protection). Thus, CCHI will NOT support hypothesis-generating, systems biology, immune profiling types of studies; and will NOT support the discovery of immune epitopes recognized by T cells or antibodies as a major research activity.

Rather, the focus is on hypothesis-testing studies to define the molecular mechanisms responsible for activating and regulating human immune functions involved in protection against infectious pathogens. In addition, the program will also include the opportunity to develop new technologies to assist in the study of the human immune system. Of the two required projects to be proposed within each application, at least one must be a hypothesis-testing research project; technology development projects may also be proposed but are optional.

Note that proposed collection of data in order to formulate a hypothesis is NOT considered to be hypothesis-testing and such approaches would not be considered responsive. Thus, the following example is NOT considered to be a hypothesis to be tested under this FOA: the collection and analysis of genome-wide gene expression data from T cells responding to typhoid vaccination will provide information on mechanisms of T cell memory generation. A hypothesis to be tested under this FOA must be based on preliminary findings, described in the application, that provide a research direction to help define an immunological mechanism through the proposed experiments. The specific hypotheses to be tested in proposed research projects should be well articulated in the application, along with the experimental plans that will address the hypotheses.

All projects must focus on human immunology in the context of infection, vaccination against infectious disease, or administration of a vaccine adjuvant(s) that targets an innate immune receptor(s). In addition, all projects must include proposed studies on primary human cells or tissues.

Exclusions - the following research areas are excluded; applications proposing studies in the excluded areas will be considered non-responsive and will not be reviewed:

• clinical trials, i.e., clinical studies testing novel interventions in humans, or using licensed interventions in a manner different from the conditions described in the intervention product’s label, are excluded; however, the use of samples obtained from human subjects in clinical trials funded through independent mechanisms is allowed;
• hypothesis-generating, systems biology, immune-profiling studies;
• projects with major emphasis on T or B cell epitope discovery or validation;
• studies using only human cell lines;
• HIV/SIV/AIDS studies;
• animal studies, except to validate the findings in human studies (also see below);
• genome-wide association studies (GWAS);
• cancer studies;
• behavioral research; and
• epidemiological studies.

CCHI applications must include Projects and Cores as described below. The allocation of funds to each component is at the discretion of the applicant, but the greatest emphasis should be placed on the Research/Technology Development Projects.

Research or Technology Development Project requirements in the application: a minimum of two and maximum of four total projects per application, to include at least one Research Project. Thus:

• if two projects are proposed, they may be one Research + one Technology Development, or two Research Projects;
• if three projects are proposed, they may be one Research + two Technology Development, two Research + one Technology Development; or three Research Projects; and
• if four projects are proposed, they may be one Research + three Technology Development; two Research + two Technology Development; three Research + one Technology Development; or four Research Projects.

Each Project must be led by a different Project Leader and must focus on human immunology and infection, vaccination, or a vaccine adjuvant(s); either in the context of testing a clearly stated hypothesis based on preliminary data, or in the context of developing a new technology or assay relevant to the proposed Research Project(s). Each Project should address a common immunological theme such that synergy is clearly evident among all the proposed Research Projects and any proposed Technology Development Projects.

Each Research/Technology Development Project must include proposed studies with primary human cells or tissues.

Activities not allowed in Research or Technology Projects: Animal Studies will not be funded unless: they are intended only to validate the findings of the human studies; their relevance to the human disease under study is clearly described in the application; AND experimental approaches are described in the Research Plan for translating the results into studies on primary human cells or tissues within the five-year funding period. If these conditions are met, then studies with nonhuman primates, humanized mice, or other relevant animal models may be proposed if they are well justified and can be supported within the budgetary constraints of the proposed research program.

Activities allowed in Research Projects: hypothesis-driven, hypothesis-testing research based on preliminary data presented in the application. Studies treating human subjects with drugs or licensed vaccines that are used for the FDA-approved purpose are not considered to be clinical trials under this FOA and may be proposed. However, note that clinical studies testing novel interventions in humans, or using licensed interventions in a manner different from the conditions described in the intervention product s label, are excluded.

The following possible research topics are listed as examples only; other topics within the scope of the program may be proposed:

• molecular mechanisms of innate immunity;
• mechanisms responsible for vaccine adjuvant efficacy or reactogenicity;
• passive immunotherapy mediated by innate immune molecules, antibodies, or soluble receptors;
• mechanisms of synergy and regulation at the innate-adaptive immune interface;
• optimization of antimicrobial T and B cell effector mechanisms to improve vaccine efficacy;
• antigen processing and presentation to T cells;
• mechanisms of mucosal immunity;
• immunoregulation in the neonate, the elderly, or the immunocompromised; and
• generation and maintenance of T and B cell memory.

Activities allowed in Technology Development Projects: research based on preliminary data presented in the application to develop one or more new technologies or assays that address the central scientific theme of the application. The following possible topics are listed as examples only; other topics within the scope of the program may be proposed:

• nano- or micro-assays that reduce required sample size;
• single cell assay development;
• development of new reagents;
• techniques to improve high-throughput screening methods;
• improved assays of immune effector function, such as antibody or cytokine production, or cytotoxic activity; and
• improved characterization of dendritic cells or other antigen-presenting cells.

Note that a Technology Development Project is not the same as a Service Core. Technology Development Projects are intended to create, validate, and refine new technologies or assays that are not currently available to any investigators. In distinct contrast, Service Cores are intended to provide investigators within the parent U19 with technologies or other services that already exist and have already been validated and refined for use.

The required Administrative Core will be responsible for the overall organization, management, decision-making, and periodic evaluations within the individual CCHI Center; as well as data-sharing, protection of intellectual property, regulatory compliance, and involvement of institutional resources.

This Core will: organize communications, group meetings, and teleconferences; organize the presentation and publication of data; allocate and re-allocate resources to meet program goals; prioritize fiscal and other resources; be responsible for resource sharing and transmission of information and reagents; manage the budget for program-related travel (including travel to the CCHI annual meetings); and identify and resolve problems and unexpected outcomes. This Core is also expected to create and implement administrative and leadership mechanisms that will foster effective interactions among the CCHI PD(s)/PI(s) and institutions to ensure a productive research effort.

In addition, the Administrative Core may support an External Scientific Advisory Group (ESAG), to be formed after award at the discretion of the PD/PI. The ESAG would evaluate scientific progress within the CCHI Center and provide advice to the Center on an annual basis.

The Administrative Core may also support an annual seminar series or symposium comprised of speakers from outside institutions to present research results on the human immunology of infection, vaccination or a vaccine adjuvant(s).

The required Pilot Project Core will support small studies to generate preliminary data for the development and submission of future research applications for support from non-CCHI sources.

The application should include plans that describe the process by which requests for pilot project support will be equitably solicited and reviewed within the U19. Thus, applicants should describe: the methods to be used for advertising the funding opportunities and for submitting applications; the size of the applications and the content to be included; the frequency of application; the rationale for excluding applicants from outside institutions, if proposed; the timeline from solicitation to funding; the process to be used to review the applications and decide on funding; and the personnel involved in the review and decision-making process. In addition, applicants should include a plan delineating methods to track the success of funded Pilot Projects, by following the number of Pilot Projects that obtain subsequent independent funding and the publications that result from each Pilot Project. Specific Pilot Projects should not be described in the application; only the process planned for soliciting Pilot Project applications, and their support and management should be described.

All Pilot Projects must focus on human immunology and infection, vaccination, or a vaccine adjuvant(s) and must include studies on primary human cells or tissues. However, the topic need not be related to other research being conducted within the parent CCHI Center. Pilot Projects that involve investigators outside the parent Center are encouraged, as are Projects that support collaborations across different CCHI Centers.

One or more optional Service Core(s) may be proposed, but only if it will be used by at least two of the Research and/or Technology Development Projects. Such Cores are limited to the provision of existing assays, reagents, technologies, clinical, statistical, informatics, or other available services to the CCHI investigators. Service Cores must be well justified and clearly non-duplicative of other services or facilities available to the CCHI PD(s)/PI(s).

Note that a Service Core is not the same as a Technology Development Project. Technology Development Projects are intended to create, validate, and refine new technologies or assays that are not currently available to any investigators. In distinct contrast, Service Cores are intended to provide investigators within the U19 with technologies or other services that already exist and have already been validated and refined for use.

Applications proposing Service Cores must indicate the specific Projects to be served by each Core and explain why the Core resources are not otherwise available.

All applications must propose an Opportunity Fund Management Core (see below for description of the Opportunity Fund). From among the successful applicants, one institution will be chosen by NIAID after award to manage the Opportunity Fund. This institution must agree to take responsibility for managing the Opportunity Fund, including the disbursement, administration, and reporting on the use of the Fund. Decisions on the use of the Fund will be made after receiving recommendations from the CCHI Steering Committee.

A Steering Committee will serve as the governing board of this collaborative research program. Its actions and decisions will be determined by majority vote. Voting members will include one PD/PI from each CCHI Center. A NIAID Project Scientist will serve as a non-voting member. Steering Committee responsibilities include:

• Evaluate progress of the individual U19 projects and provide guidance;
• Establish protocols for the review and modification of ongoing studies, which may include recommendations for new collaborations or resource allocations among the CCHI members;
• Coordinate resource sharing among the CCHI Centers;
• Assist as required in preparing formal reports summarizing activities and/or progress within the CCHI network;
• Recommend procedures to solicit applications for CCHI Opportunity Fund support, make recommendations to support specific applications through the fund, recommend budget allocations for each project to be supported through the fund, and monitor the progress of funded projects;
• Organize and convene an annual face-to-face meeting to include Steering Committee members as well as other CCHI scientists to present research progress and discuss potential collaborations between Centers; and
• Meet by teleconference once per year to discuss business issues and exchange scientific advances.

Approximately $0.5 million will be made available per year as an Opportunity Fund to support resources that provide additional assistance and/or technical expertise for projects undertaken by CCHI cooperative group investigators. Examples of possible resources include proteomics, informatics, imaging, or advanced flow or mass cytometry facilities. All projects supported by the Opportunity Fund must be within the scientific scope of the parent grant. The CCHI Steering Committee will make recommendations to the awardee of the Opportunity Fund Management Core as to the goals, priorities, and evaluation criteria for the use of the Opportunity Fund. These recommendations should include: the size and content of the applications; the frequency of application; the timeline from solicitation to funding; and the process to be used to evaluate the applications. Resources supported by the fund may be housed at particular CCHI Centers or may be supported by subawards to other facilities. Any use of opportunity funds must comply with all applicable HHS/NIH policies.

After award, one awardee institution will be selected by the NIAID to manage the Opportunity Fund for the entire CCHI program.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal The OER Glossary and the PHS 398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $20 million in FY 2014 to fund 6-7 awards.
Award Budget	Applicants may request no more than $1.75 million direct costs per year.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is five years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

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 PHS 398 Application Guide.

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

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

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

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

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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 research
• 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:

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3137, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-451-2666
Email: qvos@niaid.nih.gov

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3137, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-451-2666
Email: qvos@niaid.nih.gov

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.

• Program Overview: 12 pages
• Research Projects: 12 pages
• Technology Development Projects: 12 pages
• Core A: Administrative Core: 6 pages
• Core B: Pilot Project Core: 6 pages
• Core C-n: Service Core: 6 pages
• Core n+1: Opportunity Fund Management Core: 6 pages

Supplemental Instruction for the Preparation of Multi-Project Applications

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. All applications must be submitted on Form PHS 398. The multi-project grant application should be assembled and paginated as one complete document. Instructions for the Overall Component are presented first, followed by instructions for Research Projects, followed by instructions for Cores.

The application should consist of the following components:

• Program Overview (required)
• Research Project 1(required)
• Research Project 2 (required unless a Technology Development Project is proposed)
• Research Project 3-4 (optional)
• Technology Development Projects (1 - 3 optional)
• Core A: Administrative Core (required)
• Core B: Pilot Project Core (required)
• Core C-n: Service Core (optional)
• Core n+1: Opportunity Fund Management Core (required)

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

Description: Using Page 2 of Form 398; provide a succinct but accurate description (abstract) of the Overall multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

Project/Performance Sites: List the performance sites where the research will be conducted.

Senior/Key Personnel: Under "Key Personnel", list the PD(s)/PI(s) of the multi-project application, followed by the Research Projects and Core Leaders of the component research projects and cores, and other key personnel and then other significant contributors.

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core; prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a Composite Budget should be indicated in the "Table of Contents."

Applications must propose at least two Projects, one of which must be a Research Project, and may not propose more than four total Projects. The order of presentation within the application should be as follows:

• Form pages and composite budget as described below
• Program Overview
• Leadership Plan for Multiple PDs/PIs, if applicable
• Research Project 1
• Research Project 2-4
• Technology Development Project 1-3
• Core A: Administrative Core
• Core B: Pilot Project Core
• Core C-n: Service Core
• Core n+1: Opportunity Fund Management Core
• Biographical Sketches
• Checklist
• Appendix

Do not use Form Page 4 of PHS Form 398. Instead, using the suggested format presented below, prepare a Composite Budget for All Proposed Years of Support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component	Year 1	Year 2	Year 3	Year 4	Year 5	All Years
Research Project 1. Invest.	125,000	125,000	125,000	125,000	125,000	625,000
Research Project 2. Study	125,000	125,000	125,000	125,000	125,000	625,000
Technology Development Project. Develop.	100,000	100,000	100,000	100,000	100,000	500,000
Core A.	50,000	50,000	50,000	50,000	50,000	250,000
Core B.	25,000	25,000	25,000	25,000	25,000	125,00
Totals	425,000	425,000	425,000	425,000	425,000	2,125,000

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry. Detailed budgets are required within the descriptions of each project and core (see below).

Biographical sketches of all professional personnel for all components should be placed at the end of the entire application with the PD(s)/PI(s) first, followed by those of other key personnel in alphabetical order.

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

One Checklist, placed at the end of the application, is to be submitted for the entire application.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: This narrative section summarizes the overall research plan for the multi-project application and explains how the proposed Program satisfies the purpose and all objectives of this FOA as delineated in Section I. Applications responding to this FOA should describe the central theme of the proposed Program and explain how the proposed Research and Technology Development Projects are synergistic and fit under the overarching Program theme. The multi-project application should be viewed as a confederation of interrelated projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. If possible, provide evidence that the applicant and the proposed collaborators have prior experience in the research areas proposed, and highlight accomplishments in the field and describe the synergy and collaborations that occurred. If there was no prior experience of collaboration among the investigators, explain why the proposed investigator collaborations will result in synergy.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 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.

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide,

• For each project or core in the multi-project application, 3 publications plus other approved material are allowed.
• Please note that individual Research Projects and Cores should not contain separate appendices. Only ONE appendix may be submitted for the entire U19 application.

Except for the requirements below, follow the PHS 398 Specific Instructions in preparing each research project.

Applications must propose at least two Projects, one of which must be a Research Project, and may not propose more than four total Projects.

For each individual Research or Technology Project should include all the information listed below.

The Face Page of the 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project. This Cover Page will demarcate each individual research project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

• Project Number and Title: (e.g., 1. Cooperative Centers on Human Immunology)
• Name of Project Leader: (e.g., Jones, Roberta A.)
• Human Subjects: (Yes or No)
• If yes: Exemption number or IRB Approval Date (e.g., 07/03/2012, or Pending) and Federal wide Assurance (FWA) number
• Vertebrate Animals: (Yes or No)
• If yes: IACUC Approval Date (e.g., 07/03/2012, or Pending) and Animal welfare assurance number
• Proposed Period of Support:
• From: (mmddyyy - e.g., 07/01/2012) To: (mmddyyyy - e.g., 06/30/2017)
• Costs requested for initial budget: (e.g., 07/01/2012 - 06/30/2013)
• Direct costs: (e.g., $150,000)
• Total costs: (e.g., $162,000)
• Costs Requested for the Entire Budget Period: (e.g., 07/01/2012 - 06/30/2017)
• Direct costs: (e.g., $700,000)
• Applicant Organization (full address)

Description: Provide a Description (abstract) of the research proposed in the individual project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the individual project will contribute towards attainment of the multi-project Program objectives.

Project/Performance Sites: List the performance sites where the research will be conducted.

Key Personnel: Each Project must be led by a different Project Leader. Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Provide information on resources available for the project. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport). For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Specific Aims: List the broad long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested, or the rationale for technology development. In addition, state the individual project's relationship to the Program’s goals and how it relates to other projects or cores.

Research Strategy: Projects must focus on human immunology and infection, vaccination, or a vaccine adjuvant(s); either in the context of testing a clearly stated hypothesis based on preliminary data, or in the context of developing a new technology or assay relevant to the proposed Research Project(s). Each Project should address a common immunological theme such that synergy is clearly evident among all the proposed Research Projects and any proposed Technology Development Projects.

Each Research/Technology Development Project must include proposed studies with primary human cells or tissues.

Use this section to 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.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Results from Preliminary Studies should be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

For renewals also include in this section any progress made during the previous funding period.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 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.

Except for the requirements below, follow the PHS 398 Specific Instructions in preparing each proposed core.

For each individual Core should include all the informaton listed below.

The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

• Core Letter and Title: (e.g., A. Administrative Core)
• Name of Project Leader: (e.g., Jones, Roberta A.)
• Human Subjects: (Yes or No)
• If yes: Exemption number or IRB Approval Date (e.g., 07/03/2012, or Pending) and Federal wide Assurance (FWA) number
• Vertebrate Animals: (Yes or No)
• If yes: IACUC Approval Date (e.g., 07/03/2012, or Pending) and Animal welfare assurance number
• Proposed Period of Support:
• From: (mmddyyy - e.g., 07/01/2012) To: (mmddyyyy - e.g., 06/30/2017)
• Costs requested for initial budget: (e.g., 07/01/2012 - 06/30/2013)
• Direct costs: (e.g., $150,000)
• Total costs: (e.g., $162,000)
• Costs Requested for the Entire Budget Period: (e.g., 07/01/2012 - 06/30/2017)
• Direct costs: (e.g., $700,000)
• Applicant Organization (full address)

Description: Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the objectives.

Project/Performance Sites: List the performance sites where the core activities and services will be conducted.

Key Personnel: Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

Prepare a Table of Contents for the core using page 3 of Form PHS 398.

Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

Administrative Core

The budget request for the Administrative Core should include the costs for travel of any ESAG members to meet with CCHI personnel on an annual basis, and any additional meeting costs. A member of the CCHI program may not serve as an ESAG member for a different CCHI Center.

The budget request should also include travel funds for the PI(s)/PD(s) and Project and Core Leaders to participate in Annual Programmatic Meetings- including a kickoff meeting if held- of all Programs funded under this RFA.

Pilot Project Core

Each Pilot Project will be of limited duration (up to two years) and of limited budget (up to $50,000 direct costs/year/project). Support for a particular investigator, or for a particular project, is not allowed beyond a total of two years during the entire five year funding period. The annual direct costs for the entire Pilot Projects Core must not exceed $200,000 for all Pilot Projects. In addition, appropriate administrative costs may be included in the Core budget.

Service Cores

Applications proposing Service Cores must indicate the specific Projects to be served by that Core and explain why the Core resources are not otherwise available. The percentage of funds that will be required to support each component Research or Technology Development Project that will utilize each Core should also be presented.

Opportunity Fund Management Core

The budget request for the Opportunity Core Management Core should include the costs for a full-time Administrator as well as any other esssential personnel.

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Provide information on resources available for the core. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport). For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Specific Aims: For each of the required and optional cores, 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 it relates to two or more individual research projects or other cores in the application.

Research Strategy for Administrative Core: Note that the PD/PI of the application must serve as the Core Leader for the Administrative Core. 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.

Specific potential members of a proposed External Scientific Advisory Group (ESAG) should NOT be named in the application and ESAG members must NOT be recruited or contacted prior to review and award. However, for renewal applications, any current or former ESAG members MUST be identified in the application.

Research Strategy for Pilot Project Core: Use this section to describe how the proposed pilot project core activities will contribute to meet the CCHI Program's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should include a plan that describes how the future success of the pilot projects will be determined by following the number of projects that ultimately obtain independent funding, and the publications that result from the pilot projects.

The application should include plans that describe the process by which requests for pilot project support will be equitably solicited and reviewed within the U19. Thus, applicants should describe: the methods to be used for advertising the funding opportunities and for submitting applications; the size of the applications and the content to be included; the frequency of application; the rationale for excluding applicants from outside institutions, if proposed; the timeline from solicitation to funding; the process to be used to review the applications and decide on funding; and the personnel involved in the review and decision-making process. In addition, applicants should include a plan delineating methods to track the success of funded Pilot Projects, by following the number of Pilot Projects that obtain subsequent independent funding and the publications that result from each Pilot Project. Specific Pilot Projects should not be described in the application; only the process planned for soliciting Pilot Project applications, and their support and management should be described.

Describe the internal institutional plans and procedures to ensure that all projects supported from this award will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in project proposals, appropriate ethical oversight and funded projects, and plans for data and safety monitoring for clinical trials, if applicable.

Research Strategy for Service Core(s): One or more optional Service Core(s) may be proposed, but only if it will be used by at least two of the Research and/or Technology Development Projects. Use this section to describe how the Service Core will serve the projects and explain why the core resources are not otherwise available.

Research Strategy for Opportunity Fund Management Core: An Opportunity Fund Management Core must be proposed. Use this section to describe how the Opportunity Fund Management Core will operate to serve the CCHI consortium, including descriptions of: (1) an administrative structure that includes a full-time Administrator; (2) methods of communication with the CCHI Steering Committee regarding soliciting, evaluating, prioritizing, selecting, and monitoring the projects chosen for Opportunity Fund support; (3) methods for the disbursement and tracking of Opportunity Funds; and (4) methods for reporting on the status of the Opportunity Fund. Also describe plans and procedures to ensure that all projects supported from the Opportunity Fund will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in projects and appropriate ethical oversight.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the oPHS398 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.

Foreign (non-U.S.) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS 398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIAID, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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.

Overall Impact - Overall Score

After reviewing and scoring the individual Projects and Cores, reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the Program to exert a sustained, powerful influence on the field of human immunology, in consideration of the following review criteria.

• Is the Program as a whole scientifically compelling?
• Are there coordination and synergy of the individual Research/Technology Development Projects and Cores towards the achievement of the central objectives of the Program?
• Are the overall Program goals significant and focused on studies that meet the purpose and objectives of the RFA?
• Will the integration of the individual Research/Technology Development Projects into a single Program be more beneficial than pursuing each project independently?
• Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research Program?
• Is there adequate evidence of sufficient institutional support for the PD(s)/PI(s) in terms of laboratory space, equipment and other resources?
• For applications designated multiple PD(s)/PI(s), is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PD(s)/PI(s)?
• Is the Program sufficiently focused on the study of mechanisms by which the human immune system is activated and regulated?
• Do the applicant and proposed collaborators have prior and productive experience in the proposed research areas and have their accomplishments made a significant impact on the field of immunology?
• For renewal applications, was substantial progress made in the preceding period of support?

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria.

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, and technologies that drive this field? Are new principles of human immunology likely to be described through the proposed efforts? For Research Projects, do the preliminary data support the stated hypotheses to be tested? Are the proposed mechanisms likely to play important roles in human immune activation and regulation? For Technology Development Projects, is there a compelling need for the new technology within the proposed CCHI research program? Is there potential benefit to the scientific community at large, for a variety of biomedical research applications?

Investigator(s)

Are the Project Leaders, 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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research 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?

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? Are there sufficient plans for statistical and informatics support?

Are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is there sufficient focus on hypothesis-testing, mechanistic studies of the human immune system? Do the hypotheses address mechanisms of human immune function or regulation?

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/priority score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria.

Reviewers will provide an overall impact/priority score for each Core to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria.

Administrative Core

• Is 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 PI(s)/PD(s), Projects and Core Leaders adequate to manage 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 the establishment of a strong collaborative environment for the program appropriate?
• Are the plans for resource allocation within the U19 adequate and appropriate?
• Is the management plan for fiscal accountability and communication within the Program appropriate?

Pilot Project Cores

• Are the methods proposed to solicit and review pilot project applications appropriate?
• Are the personnel charged with reviewing pilot project applications appropriate?
• Are the personnel charged with deciding on funding pilot project applications appropriate?
• Is the method to track the success of the pilot projects adequate and appropriate?
• Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Service Cores

• Is provision of the proposed core services to the Research/Technology Development Projects critical and justified?
• Is the relationship of the core to the central focus of the overall Program strong?
• Are the quality of the relevant facilities or services provided (including procedures, techniques, quality control) and criteria for prioritization and usage appropriate?
• Are the proposed personnel appropriate to lead and staff the proposed core?

Opportunity Fund Management Core

• Is provision of the proposed core services to the CCHI program described in sufficient detail?
• Is sufficient justification provided for the management methods proposed?
• Are the personnel charged with managing the Opportunity Fund appropriate?
• Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, and appropriate ethical oversight of funded projects?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

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

Revisions

Not Applicable

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

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

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.

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 as follows:

• 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;
• The PD/PI will be responsible for defining the research objectives, approaches, and details of the projects within the guidelines of the FOA and has primary responsibility for the planning, directing, and executing of the proposed scientific activities;
• The PD/PI will be responsible for negotiating research milestones and timelines with the assigned NIAID program official, and for monitoring the successful completion of the milestones within the timeframe and budget proposed;
• The PD/PI will ensure that results obtained under this program are analyzed and published in a timely manner;
• The PD/PI will be responsible for establishing and managing an External Scientific Advisory Group (ESAG) for the individual CCHI center, if desired; however, an ESAG is not required for any center;
• The PD/PI will host site visits by NIAID program staff as requested by the program staff;
• One PD/PI from each CCHI Center will be a voting member of the CCHI Steering Committee, will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee; and
• One awardee institution will be selected by NIAID after award to administer the Opportunity Fund; the institution will agree to manage the fund, including the disbursement, administration, and reporting on the use of the Opportunity Fund to the Steering Committee.

Federally Mandated Regulatory Requirements for Clinical Research

Each institution participating in clinical research is required to meet DHHS regulations for the protection of human subjects. At a minimum, this includes: methods for assuring that each institution at which CCHI investigators are conducting clinical studies has registered with the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp) and has a Federal Wide Assurance; when relevant, methods for assuring or documenting that each participant’s parent or legal guardian gives fully informed consent to participation in a research protocol prior to the initiation of a study;

that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to participant entry; and that active protocols are reviewed at least annually by the IRB and that amendments are approved by the IRB.

Intellectual Property

The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the awardee to perform the project. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project. The awardee is required to report to the U.S. Government all inventions made in performance of the project, as specified by 35 U.S.C. Sect. 200-212 (Bayh-Dole Act).

Program Generated Data, Software, and Other Resources

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 HHS, PHS, and NIH policies. However, awardees are expected to be committed to making research samples and tools, methods, data, and materials that they develop under the CCHI program available to other CCHI centers and the research community, consistent with achieving the goals of this program.

Publications

The PD/PI will be responsible for the timely submission to the NIAID of all abstracts, manuscripts, and review articles authored by members of the grant and supported in whole or in part under this Cooperative Agreement. The PD/PI is requested to provide manuscripts to the NIAID program staff at the time of acceptance by a journal so that an up-to-date summary of the program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD/PI and appropriate Project and Core Leaders and will require appropriate acknowledgement of NIAID support. Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms.

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

An NIAID Program Official will be responsible for the normal scientific and programmatic stewardship of each award and will be named in the award notice. Additionally, an NIAID Program Official will serve as the Project Scientist for the CCHI program and will work closely with the Steering Committee and other CCHI member scientists to:

• Provide input into the design of research activities;
• Play a key role in coordinating research efforts;
• Participate in investigator and Steering Committee meetings;
• Facilitate collaborations with and access to other NIAID-supported research resources and services;
• Advise in project management and technical performance;
• Serve as liaison/facilitator between the awardees;
• Serve as a resource for scientific and policy information related to the goals of the awardee’s research;
• Provide oversight for human subjects protections;
• Organize the Steering Committee meetings;
• Attend investigator and Steering Committee meetings;
• Ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies; and
• Provide guidance to the awardees with regard to:
• Compliance with Federal regulations;
• Oversight and monitoring of collaborative research;
• Feasibility of timely completion; and
• Plans for incorporation of new technologies or other resources.

Areas of Joint Responsibility include:

Steering Committee membership: the CCHI network will be governed by a Steering Committee to coordinate and facilitate research activities for the overall program, to ensure optimal research flexibility, synergy, and efficiency. The Steering Committee will include one PD/PI from each awarded U19 as a voting member, each with one vote; and will include the NIAID Project Scientist as a non-voting member. Other individuals with expertise in relevant scientific areas may also be included as non-voting members. A Steering Committee Chair will be elected annually by majority vote of the voting Steering Committee members. The CCHI Steering Committee will meet once a year by teleconference and once a year at an annual face-to-face scientific meeting.

Steering Committee duties include:

• Evaluate progress of the individual U19 projects and provide guidance;
• Establish protocols for the review and modification of ongoing studies, which may include recommendations for new collaborations or resource allocations among the CCHI members;
• Coordinate resource sharing among the CCHI Centers;
• Assist as required in preparing formal reports summarizing activities and/or progress within the CCHI network;
• Recommend procedures to the awardee of the Opportunity Fund Management Core to solicit applications for CCHI Opportunity Fund support, make recommendations to support specific applications through the fund, recommend budget allocations for each project to be supported through the fund, and monitor the progress of funded projects;
• Organize and convene an annual face-to-face meeting to include Steering Committee members as well as other CCHI scientists to present research progress and discuss potential collaborations between Centers; and
• Meet by teleconference once per year to discuss business issues and exchange scientific advances.

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 will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Helen Quill, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-4416
Email: hquill@niaid.nih.gov

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2666
Email: qvos@niaid.nih.gov

Julia Shriner
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2690
Email: Julia.Shriner@nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.