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 using ASSIST or an institutional system-to-system solution; 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.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) 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

The Cooperative Centers on Human Immunology (CCHI) program was initiated by NIAID in 2003 to foster research in human immunology. The original program goals were defined following recommendations from several expert panels convened to identify research needs in the area of biodefense. The current CCHI program supports the translation of immunology research into clinical applications in humans, primarily in the area of infectious diseases. The objective of this Funding Opportunity Announcement (FOA) is to support mechanistic and hypothesis-testing studies to understand human immunity applicable to the biodefense effort; i.e. innate, adaptive and mucosal immune responses to infection, vaccination and adjuvants. The FOA will also support studies on mechanisms leading to immune-mediated diseases, where such studies serve as tools to provide a more comprehensive understanding of the human immune system. All studies must focus on mechanisms of the activation and regulation of human immune responses. The program will also support a centralized infrastructure that will promote and coordinate multi-disciplinary research in human immunology. CCHI is non-overlapping and complementary to DAIT's Human Immunology Project Consortium (HIPC). While both programs focus on human immunology, CCHI supports mechanistic studies while HIPC supports data-gathering, hypothesis-generating studies.

The CCHI program has supported many leading advances in immunology that impact our fundamental understanding of the human immune system. For example, recent studies have provided evidence that immune variability can be explained by non-heritable influences; multi-cohort analyses have identified common host signatures that can distinguish individuals with viral infections from bacterial infections or healthy controls; the gut microbiota has been shown to play a key role in antibody responses to vaccination; and Fc glycan modification of antibodies have been implicated in the regulation of the humoral immune responses in viral infections. Technological advances developed through CCHI support include: the application and further development of CyTOF to immunological research; development of Multiplexed Ion Beam Imaging (MIBI); Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq); and methodologies enabling integration of information about T cell receptor (TCR) specificity with information about T cell function. In addition, CCHI has supported training in sophisticated technologies for researchers across the country.

While many strides have been made in the study of human immune responses, numerous knowledge gaps still remain. Many infections and immune-mediated diseases are localized to specific tissues or organs but little is known about tissue/organ-specific immunity. A majority of the studies in the field continue to use cells derived from blood, but there is a dearth of information on whether peripheral responses correlate to that seen in tissues/organs. Response to infection or vaccination in the presence of immune-modulating co-morbidities (e.g. diabetes, age, obesity) also needs to be investigated, as does the impact of the intestinal microbiome on these responses. Studies in "trained immunity" could revolutionize our views of immunological memory in innate cells and lead to defining new classes of vaccines and immunotherapies. While the molecular mechanisms of trained immunity have not been elucidated, epigenetic changes may play a role and studies to comprehend the role of epigenetic modifications in regulating the immune system are needed. More recently, metabolic changes that can impact the proliferative potential, differentiation and function of immune cells are being investigated and the metabolomic-immune connection remains an important axis that could be potentially targeted to modulate immune responses. New technologies and assays will be required to meet the challenges of studying the human immune response; for example, analyses of interactions of immune cell populations in vivo is a challenge and may require the development of new imaging technologies. Therefore, CCHI will continue to support the development of new technologies and assays.

The CCHI program will support mechanistic and hypothesis-testing studies that advance mechanistic understanding of host defenses applicable to the biodefense effort, i.e. innate, adaptive and mucosal immune responses to infection, vaccination and adjuvants. Studies on mechanisms leading to immune-mediated diseases (e.g., airway allergy, food allergy, autoimmunity, organ transplant rejection) are also of interest, where such studies synergize with required studies on immunity to pathogens/vaccines to advance understanding of human immunity. Within the application, at least one project must be focused on understanding host immunity applicable to immunity to infectious diseases, vaccines or adjuvants. A project on immune-mediated disease is not a requirement, but is permitted.

Applications are expected to be synergistic and contain Research Projects and Cores connected by a common theme that produce scientific gains beyond those achievable if each project were pursued independently. For example, an application may include different infections, vaccines, adjuvants and/or immune-mediated diseases to examine common immune pathways/mechanisms; or may analyze various aspects of the immune response to the same infection, vaccination or adjuvant. The focus of the overall application should advance our understanding of human immunity through analysis of human samples. However, animal studies may be included to extend or guide mechanistic analyses of human samples. While this FOA does not support vaccine or product development, the FOA will support clinical trials where the primary objective is to obtain human samples for mechanistic studies of immune function. Such mechanistic trials include: administering licensed vaccines either in accordance with FDA guidance or off-label in terms of timing, cohorts, etc.; and pathogen exposure/challenge studies. The inclusion of human samples obtained from independently funded clinical trials is also permitted.

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

• Research Projects:
• Mechanisms of tissue/organ-specific and mucosal immunity;
• Molecular mechanisms of innate immunity, including trained immunity;
• Mechanisms responsible for adjuvant efficacy or reactogenicity;
• Mechanisms of synergy and regulation at the innate-adaptive immune interface;
• Mechanisms regulating generation and maintenance of T and B cell memory;
• Mechanisms regulating exhaustion of the immune response to chronic infection/exposure, and impact on vaccine responses;
• Effect of the microbiota on immune responses;
• Epigenetic and/or metabolic regulation of the immune response; and
• Immunoregulation pathways, including control of inflammatory processes;
• Technology Development Projects:
• Studies to develop one or more new technologies or assays that support the central scientific theme of the application;
• Nano- or micro-assays to reduce required sample size;
• Single cell assay development;
• Development of new reagents to study human immunity;
• Techniques to improve high-throughput screening methods;
• Computational tools for analyzing human immune responses and interpolating data generated from animal studies;
• Imaging technologies for analyses of in vivo immune responses;
• Improved assays of immune effector function, such as antibody or cytokine production, or cytotoxic activity.

Applications that propose studies in the following areas will be considered non-responsive and will not be reviewed:

• Applications that are not focused on mechanisms of the activation and regulation of human immune responses;
• Applications that do not include at least one Research Project focused on understanding host defenses applicable to the biodefense effort; i.e., innate, adaptive and mucosal immune responses to infection, vaccination and adjuvants;
• Applications focused on vaccine or product development for infectious or immune-mediated disease specific indications;
• Applications that do not include the use of primary human cells, fluids or tissue in Research Projects;
• Large scale immune profiling studies to generate hypotheses in the absence of mechanistic studies;
• Clinical trials in which the primary objective is to test the safety or efficacy of an investigational vaccine, adjuvant or other product;
• Projects with primary focus on T or B cell epitope discovery or validation;
• HIV/SIV/AIDS studies;
• Development of new animal models;
• Genome-wide association studies (GWAS);
• Cancer studies, except those examining immune responses to infectious diseases or pathogen-specific vaccines in cancer patients; and
• Behavioral research or epidemiological studies.

Collaborative Interdisciplinary Teams

The scope of this work requires that interdisciplinary teams be formed that are capable of pursuing coordinated activities that bridge scientific disciplines and expertise in immunology, infectious diseases, vaccinology, immune-mediated diseases, omics technologies and bioinformatics. Bringing multidisciplinary groups together creates opportunities for synergy that would rarely happen otherwise. The research teams within each center may be composed of investigators located at one institution, or may be formed through a consortium of different institutions.

CCHI Program Components

Administrative Core: The Administrative Core will be responsible for managing, coordinating and supervising the entire range of the center's activities; monitoring progress; ensuring that the overall project management plan is implemented effectively and within proposed timelines; and data-sharing and regulatory compliance.

Infrastructure and Opportunity Fund Management Core: To capitalize on emerging opportunities consistent with the goals of the CCHI, an Infrastructure and Opportunity Fund (IOF) will be made available to one institution chosen from successful applicants by NIH after award, to manage for the entire CCHI program. This institution must agree to take responsibility for managing the IOF, and includes establishing an administrative structure, disbursement and tracking of funds, and reporting status. Examples of activities supported by the IOF may/could include pilot projects and development projects; resource development and sharing opportunities; translational projects; and early stage investigator projects. IOF projects must be within the scope of this FOA and may be submitted by CCHI awardees or by outside investigators.

Service Core(s): Service Cores will provide CCHI investigators with pre-existing technologies or services that have already been validated and refined for use (for example, existing assays, reagents, technologies, clinical, statistical, informatics, or other services). One of these Service Cores may be a Clinical Core that provides human cells/samples to Projects and Cores and/or conducts mechanistic clinical trials. A Service Core must be used by at least two of the Research and/or Technology Development Projects.

Research Projects: Each center must propose at least two milestone-driven mechanistic, hypothesis-testing immunology Research Projects, which advance our understanding of the mechanisms regulating human immune responses.

Technology Development Project: The Technology Development Project is intended to create, validate, and refine new or significantly enhance existing technologies, assays or computational tools for analyzing human immune responses that are not currently available to any investigators. A Technology Development project may be included, but is not required.

Steering Committee: A Steering Committee will be established by NIAID with the awardees to serve as the governing body of the CCHI. This committee will promote scientific collaboration and exchange of scientific findings among the centers. It will also assist in making recommendations for applications submitted for CCHI IOF.

External Advisory Board (EAB): An EAB will be convened by NIAID to advise NIAID by reviewing and evaluating the scientific progress of the individual CCHI awardees and the CCHI program as a whole. EAB members will be selected by NIAID after award and should not be proposed by applicants.

External Scientific Advisory Group (ESAG): An ESAG may be formed after award at the discretion of the PD(s)/PI(s) to evaluate and advise on scientific progress within the awarded center.

Milestones and Timelines: The program must have annual "Milestones and Timelines" with clearly stated objectives.

Note: All CCHI Program Directors /Principal Investigators (PDs/PIs) funded under this FOA will be required to submit their data into the ImmPort database or other publicly accessible database approved by NIAID.

Note: Under urgent public health situations, the NIAID may re-direct funds or provide additional funds to individual awards to support research of direct relevance to the emergency.

Note: For more information please refer to the Questions and Answers web site for this FOA.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (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 the PD/PI on only one U19 application submitted in response to this FOA.

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).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core	6 pages
Core (use for Infrastructure and Opportunity Fund Management Core, Service Core[s])	6 pages
Project (use for Research Projects, Technology Development Project)	12 pages

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Infrastructure and Opportunity Fund Management Core: required, maximum of 1
• Service Core(s): optional, maximum of 3
• Research Projects: required, minimum of 2, maximum of 3
• Technology Development Project: optional, maximum of 1

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.

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.

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

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

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

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

Research Strategy:

• Summarize the overall research plan for the multi-project application and explain how the proposed research supports mechanistic studies on the activation and regulation of human immune responses.
• Describe the central theme of the proposed research and explain how the proposed Research Projects and Technology Development Project (if applicable), are interrelated, synergistic and fit under an overarching common theme and provide scientific gains beyond those achievable if each project were pursued independently. As the strategy develops, cite each project and core briefly as to its place in the overall scheme;
• Briefly describe the human populations and the rationale for their selection for each Project and Core. Describe how the study of these populations will enhance the goals of the overall center;
• Include a schematic overview (figure) of the interactions, synergy and collaborations among the project components;
• Describe prior or on-going collaborations among the investigators. If there was no prior experience of collaboration among the investigators, explain why the proposed investigator collaborations will enhance the proposed studies; and
• Include annual Milestones and Timelines for the entire application.

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:

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

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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

• For applications that include mechanistic Clinical Trials that span components: Explain how the proposed clinical trials will support the center's common theme; how samples will be used across/within relevant project(s) and/or core(s); and how sample distribution and communication will be managed throughout the proposed center.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application 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.
• The PD/PI of the application must serve as the Administrative Core Lead.

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

• Include travel funds for one to-be-named External Advisory Board (EAB) member to attend the CCHI annual face-to-face meeting, to be held in the Bethesda/Rockville, MD area (2 days per annual meeting);
• Include travel funds for the PD(s)/PI(s) to attend the CCHI annual face-to-face meeting, to be held in the Bethesda/Rockville, MD area (2 days per annual meeting);
• Include costs associated with the center's submission of data into the ImmPort database or other publicly accessible database approved by NIAID (as appropriate); and
• If applicable, include the costs of travel for any to-be-named External Scientific Advisory Group (ESAG) members to meet with CCHI personnel on an annual basis, and any additional meeting costs.

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

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

Research Strategy:

• Provide a staffing and administrative plan that includes a discussion of the structure, roles, responsibilities, and functions to be performed by the Core administrative and scientific staff. The plan should also detail how resources will be acquired, prioritized, allocated and managed;
• Provide a management plan for fiscal accountability and communication within the center, including plans to organize communications, group meetings and teleconferences;
• Provide a plan for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the center; and
• An External Scientific Advisory Group (ESAG), may be formed after award at the discretion of the PD(s)/PI(s) to evaluate and advise on scientific progress within the center. For renewal applications: identify any current or former ESAG members. New applications should not name, recruit or contact potential ESAG members.

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

Appendix:

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

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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 (Infrastructure and Opportunity Fund Management Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Infrastructure and Opportunity Fund Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Infrastructure and Opportunity Fund Management Core)

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

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

Project Narrative: Do not complete. 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) (Infrastructure and Opportunity Fund Management Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Infrastructure and Opportunity Fund Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Multiple Core Leads are not permitted for IOF Management Core.

Budget (Infrastructure and Opportunity Fund Management Core)

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

IOF Management Core application budgets should include the following costs:

• (i) a maximum of 2 person months' effort for the IOF Management Core Leader; and (ii) a minimum of 4 person months' effort for an IOF administrator and administrative staff (combined), as needed, to be included in the Other Personnel category, the total not to exceed $150,000 direct costs per year.
• IT computing supplies, if required.
• Direct costs for a maximum of $750K per year to support a maximum of ten projects per year. These can be a combination of development projects (not to exceed $150K direct costs/year) and/or pilot projects (not to exceed $50K direct costs/year) to be included in the Other Direct Costs category for the remaining funds.
• Include funds for travel for the IOF Management Core Leader to attend the CCHI annual meeting, to be held in the Bethesda/Rockville, Maryland area (2 days per annual meeting), if needed.

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 (Infrastructure and Opportunity Fund Management Core)

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

Research Strategy: The IOF management plan should include:

• An administrative structure;
• Plans for the solicitation, evaluation, selection and award of Pilot projects and Development projects;
• Proposed procedures to implement Steering Committee IOF recommendations in a timely; manner, including the time interval for establishment and renewal of consortium agreements;
• Tracking and monitoring of timely submission and payment of invoices, and plans for handling consortium agreement administration delays;
• Plans for interacting with the institutions that will receive IOF funds;
• Reporting on the status of the funds and consortium agreements awarded;
• Providing an IOF administrator and/or other staff, as needed, to coordinate these activities with the NIAID, CCHI Steering Committee and the institution’s grants and contracts staff; and
• Include a statement of commitment from the Institution’s signing official agreeing to take fiscal responsibility for the management of the Infrastructure and Opportunity Funds, if chosen by NIAID to administer the fund.

Note: This section should only include information about the management of the IOF and should not include any IOF proposed research projects.

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

PHS Human Subjects and Clinical Trials Information (Infrastructure and Opportunity Fund Management Core)

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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.

• Include travel funds for the Service Core Leader, and up to two (2) additional scientific staff, to participate in the CCHI annual face-to-face meeting, to be held in the Bethesda/Rockville, MD area (2 days per annual meeting).
• Include costs associated with the Core's submission of data into the ImmPort database or other publicly accessible database approved by NIAID (as appropriate), when such costs are not included in the Administrative Core;
• If a Clinical Core is proposed and includes a CCHI-funded clinical trial or study, include the following costs, when such costs are not included in the Projects: clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the CCHI 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, and capturing and reporting adverse events related to any intervention or procedure and handling protocol deviations.
• For Cores (Clinical or otherwise) obtaining samples from independently-funded clinical trials, include the following costs, when such costs are not included in the Projects: additional clinical trial-related activities such as the costs of re-consenting study participants, preparation of protocol or IND amendments, and additional sample collection, preparation, and shipping.

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

PHS 398 Research Plan (Service Core)

Specific Aims: List in priority order the broad, long-range activities and services of the Service Core(s). In addition, state the Core’s relationship to the center’s goals.

Research Strategy: Describe the reagents, resources, technologies or other services to be provided by the Service Core and why the proposed services or resources are non-duplicative of other services or facilities available to the CCHI PD(s)/PI(s). Describe how it will serve two or more individual Research and/or Technology Development Projects. Explain how requests will be prioritized and coordinated.

Letters of Support: Provide letters of support from collaborators that are applicable to the Service Core, including a Memorandum of Understanding (MOU) or Materials Transfer Agreement (MTA) that documents availability and/or access to human materials for each source (i.e., sample availability corresponding to the outlined Timelines and Milestones).

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

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

PHS Human Subjects and Clinical Trials Information (Service Core)

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

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

For a Core proposing the use of, or supporting projects that will use non-exempted human samples to be obtained from independently-funded clinical trials include the following:

• Summary table of events including: the volume of blood, or amount of tissue, collected for the proposed studies.

Study Record: PHS Human Subjects and Clinical Trials Information

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

For studies involving the use of identifiable human biospecimens collected from independently funded clinical research or clinical trials, applicants should include both historical and current study information that is clearly distinguishable within the information requested in the study record forms.

Section 2 - Study Population Characteristics

Section 2.7 - Study Timeline

If applicable, timelines should address the time needed to acquire samples from independently-funded clinical research or clinical trials.

Inclusion Enrollment Report(s)

For studies using an existing dataset, applicants must fill out the Enrollment Location(s) in field 4.

Section 3 Protection and Monitoring Plans

Section 3.3 - Data and Safety Monitoring Plan

Include a description of the appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring, safety monitoring, regulatory submissions and quality management (Note: this is in addition to what is included in the standard instructions for the Data Safety Monitoring Plan).

Section 5 Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Include a description of the plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.

Delayed Onset Study

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

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 Projects)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

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

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

Project Narrative: Do not complete. 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) (Research Projects)

List all performance sites that apply to the specific component.

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

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

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

Budget (Research Projects)

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

• Include travel funds for the Project Leader and up to three (3) additional scientific staff per project to attend the CCHI annual face-to-face meeting, to be held in the Bethesda/Rockville, MD area (2 days per annual meeting);
• Include costs associated with the Project's submission of data into the ImmPort database or other publicly accessible database approved by NIAID (as appropriate), when such costs are not included in the Administrative Core;
• If samples for the proposed studies are to be collected from a CCHI-funded clinical trial or study include the following costs, when such costs have not been included under a Service Core: clinical protocol development, informed consent form development, development of a manual of procedures for each clinical protocol that the CCHI 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, and capturing and reporting adverse events related to any intervention or procedure and handling protocol deviations.
• If samples for the proposed studies are to be collected from an independently-funded clinical trial include the following costs, when such costs have not been included under a Service Core: the costs of re-consenting study participants, preparation of protocol or IND amendments, and additional sample collection, preparation, and shipping.

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

PHS 398 Research Plan (Research Projects)

Specific Aims: List the broad long-range objectives and goals of the proposed project. Describe the hypothesis or hypotheses to be tested, or the rationale for technology development. In addition, state the individual project's relationship to the center's goals and how it relates to other Projects or Cores.

Research Strategy:

Describe how the proposed studies will utilize primary human immune cells, fluids or tissues, and if needed, relevant animal models, to provide mechanistic insights that will advance our understanding of human immune function or regulation applicable to the: (1) biodefense effort, i.e., adaptive and mucosal immune responses to infection, vaccination and adjuvants; or (2) immune-mediated diseases (if applicable);

• Explain the rationale for selecting the methods and approaches to accomplish the specific aims, including selection of sample sources;
• State the biological significance of the research. Explain how the Research Project addresses the common immunological theme of the application and how the project contributes to the overall goals of the center;
• Include a data and/or statistical analysis plan that describes how data will be analyzed. For clinical trials, applicants will provide specific statistical design and power information under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy;
• Justify the inclusion of any animal studies, explain how they will provide mechanistic insights into immune function or regulation, and discuss how they will extend/complement the findings of proposed human studies;
• In a clearly labeled section, describe annual milestones and timelines for the overall project. For clinical trials, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.

Letters of Support: Provide letters of support from collaborators that are applicable to the Research Project, including a Memorandum of Understanding (MOU) or Materials Transfer Agreement (MTA) that documents availability and/or access to human materials for each source (i.e., sample availability corresponding to the outlined Timelines and Milestones).

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

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

PHS Human Subjects and Clinical Trials Information (Research Projects)

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

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

For Research Projects proposing the use of, or supporting projects that will use non-exempted human samples to be obtained from independently-funded clinical trials include the following:

• Summary table of events including: the volume of blood, or amount of tissue, collected for the proposed studies.

Study Record: PHS Human Subjects and Clinical Trials Information

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

For studies involving the use of identifiable human biospecimens collected from independently-funded clinical research or clinical trials, applicants should include both historical and current study information that is clearly distinguishable within the information requested in the study record forms.

Section 2 - Study Population Characteristics

Section 2.7 - Study Timeline

If applicable, timelines should address the time needed to acquire samples from independently funded clinical research or clinical trials.

Inclusion Enrollment Report(s)

For studies using an existing dataset, applicants must fill out the Enrollment Location(s) in field 4.

Section 3 - Protection and Monitoring Plans

Section 3.3 - Data and Safety Monitoring Plan

Include a description of the appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring, safety monitoring, regulatory submissions and quality management (note: this is in addition to what is in the Data Safety Monitoring Plan).

Section 5 Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Include a description of the plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.

Delayed Onset Study

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

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 (Technology Development 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 (Technology Development Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Technology Development 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.

Project /Performance Site Location(s) (Technology Development 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 (Technology Development 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 (Technology Development Project)

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

• Include travel funds for the Project Leader and up to three (3) additional scientific staff per project, to attend the CCHI annual face-to-face meeting, to be held in the Bethesda/Rockville, MD area (2 days per annual meeting).
• Include costs associated with the Project's submission of data into the ImmPort database or other publicly accessible database approved by NIAID (as appropriate), when such costs are not included in the Administrative Core.

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 (Technology Development Project)

Specific Aims: List the broad long-range objectives and goals of the proposed project. Describe the hypothesis or hypotheses to be tested, or the rationale for technology development. In addition, state the individual project's relationship to the center's goals and how it relates to other Projects or Cores.

Research Strategy:

• Describe how the proposed research will develop a new or significantly enhance an existing technology(ies), assay(s) and/or computational tool(s) relevant to the proposed Research Project(s) and the rationale for selecting the methods to accomplish the specific aims;
• Discuss how the proposed research will address an unmet need that contributes to the common theme of the application;
• State the biological significance of the research. Explain how the Project addresses the common immunological theme of the application and how the project contributes to the overall goals of the center;
• In a clearly labeled section, describe annual milestones and timelines for the project. If Clinical Trials are included, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.

Letters of Support: Provide letters of support from collaborators that are applicable to the Technology Development Project, including a Memorandum of Understanding (MOU) or Materials Transfer Agreement (MTA) that documents availability and/or access to human materials for each source (i.e., sample availability corresponding to the outlined Timelines and Milestones).

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

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

PHS Human Subjects and Clinical Trials Information (Technology Development Project)

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

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

For Technology Development Projects proposing the use of, or supporting projects that will use non-exempted human samples to be obtained from independently-funded clinical trials include the following:

• Summary table of events including: the volume of blood, or amount of tissue, collected for the proposed studies.

Study Record: PHS Human Subjects and Clinical Trials Information

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

For studies involving the use of identifiable human biospecimens collected from independently-funded clinical research or clinical trials, applicants should include both historical and current study information that is clearly distinguishable within the information requested in the study record forms.

Section 2 - Study Population Characteristics

Section 2.7 - Study Timeline

If applicable, timelines should address the time needed to acquire samples from independently funded clinical research or clinical trials.

Inclusion Enrollment Report(s)

For studies using an existing dataset, applicants must fill out the Enrollment Location(s) in field 4.

Section 3 - Protection and Monitoring Plans

Section 3.3 - Data and Safety Monitoring Plan

Include a description of the appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring, safety monitoring, regulatory submissions and quality management (note: this is in addition to what is in the Data Safety Monitoring Plan).

Section 5 Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Include a description of the plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.

Delayed Onset Study

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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

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

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit 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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. 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.

In addition, for applications involving clinical trials:

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

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

• Is the application as a whole scientifically compelling?
• Is the application sufficiently focused on the study of mechanisms by which the human immune system is activated and regulated?
• Is the application cohesive in terms of projects and cores fitting into a common theme?
• Are there coordination and synergy of the individual Research/Technology Development Projects and Cores towards the achievement of the central objectives of the application? Will the integration of the individual Research/Technology Development Projects into a single application 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? 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)?
• Are the Overall annual Milestones and Timelines proposed appropriate and feasible?

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

• Are new principles of human immunology likely to be discovered through the proposed efforts?
• Are the goals of the Project relevant to the primary theme of the overall application?
• 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 the Technology Development Project: Is there a compelling need for the new technology within the proposed center? Is there potential benefit to the scientific community at large, for a variety of biomedical research applications?

In addition, for applications proposing clinical trials

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

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

In addition, for applications proposing clinical trials

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

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

In addition, for applications proposing clinical trials

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

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Research Projects:

• 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?
• Are the data and/or statistical analyses plans acceptable (for non-clinical trial projects)?
• If animal studies are proposed, is the justification for their inclusion adequate and will they extend the findings of human studies?
• Are the annual milestones and timelines proposed appropriate and feasible?

Technology Development Project (where applicable):

• Will the proposed research develop a new or significantly enhanced technology, assay or computational tool?
• Does the project address an unmet need that contributes to the common immunological theme amongst all of the proposed Research Projects?
• Are the annual milestones and timelines proposed appropriate and feasible?

In addition, for applications proposing clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable? Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP) compliance, if applicable?

Data Management and Statistical Analysis

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

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

In addition, for applications proposing clinical trials

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

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

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

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

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, in consideration of the following review criteria and additional review criteria (as applicable for the core proposed).

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

Administrative Core

• Is the staffing and administrative plan appropriate to facilitate attainment of the objectives of the proposed center?
• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the overall center?
• 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 center appropriate?
• Are the plans for resource allocation within the center adequate and appropriate?
• Is the management plan for fiscal accountability within the center appropriate?
• Are the designated personnel sufficient to enable compliance with the data-sharing and other resource sharing policy?

Service Core(s) (if applicable)

• Is provision of the proposed Core services to the Research and Technology Development Projects critical and justified?
• Is the relationship of the Core to the central focus of the overall center strong?
• Are the experience, qualifications, level of commitment, and availability of the Core Leader adequate to manage the Core? Are the experience, qualifications and level of commitment of the staff adequate?
• 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, including collaborators/consultants, appropriate to staff the proposed Core?
• For Clinical Cores or Cores involving human subjects and/or NIH-defined clinical research (if applicable), 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 addition, for Service Cores proposing clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable? Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP) compliance, if applicable?

Data Management and Statistical Analysis

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

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

Infrastructure and Opportunity Fund (IOF) Management Core

• Is provision of the proposed IOF management services to the "program" described in sufficient detail?
• Is sufficient justification provided for the management methods proposed for the IOF?
• Are the personnel charged with managing the IOF appropriate?

Study Timeline

Specific to This FOA: In those studies using identifiable human biospecimens collected from independently-funded clinical research or clinical trials, are the timeline and documentation adequate/feasible to successfully obtain the samples and implement the proposed project(s)?

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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

Not Applicable

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

Not Applicable

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

Not Applicable

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

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

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

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• One PD/PI from each center will be a voting member of the Steering Committee.
• All CCHI investigators will be required to implement policies approved by the Steering Committee.
• The PD/PI are expected to share all CCHI-supported data publicly through ImmPort or other public portals designated by NIAID, consistent with achieving the goals of the program. 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 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.

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

• 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.
• Facilitate collaborations with and access to other NIAID-supported research resources and services.
• Serve as liaison/facilitator among awardees and with the ImmPort database.
• 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.
• Establish an External Advisory Board (EAB) to advise NIAID by reviewing, evaluating, and prioritizing the scientific progress of the individual awardees and the network.
• 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

The Steering Committee will serve as the governing body of the CCHI and will assist in making recommendations for applications submitted for CCHI IOF.

Infrastructure and Opportunity Fund (IOF): The NIH Project Scientist and PD(s)/PI(s) from the funded projects will establish a Steering Committee. The Steering Committee will oversee the Infrastructure and Opportunity Fund, consistent with the goals of the program. The Steering Committee will devise and implement procedures, practices, and subcommittees as needed, for the IOF solicitation, receipt, review, development, evaluation, and recommendation of pilot projects, development projects, resource development, or potential resource sharing opportunities and other collaborative needs.

• Each CCHI center will be represented by one PD/PI as a voting member of the Steering Committee. NIAID Project Scientists will be non-voting members.

External Scientific Advisory Group

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 will evaluate scientific progress within the CCHI center and provide advice to the center on an annual basis.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons 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
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Lakshmi Ramachandra, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5061
Email: [email protected]

Paul Amstad, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5067
Email: [email protected]

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

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.