It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This FOA solicits applications from single institutions, or consortia of institutions, to participate in the Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG) program. The overarching goals of the NHPCSG are to: (1) develop novel immune tolerance induction regimens; (2) evaluate preclinical safety and efficacy of existing and newly developed candidate immune tolerance induction regimens; (3) develop and validate biomarkers for induction, maintenance and/or loss of immune tolerance or for prediction of graft rejection; and (4) elucidate mechanisms underlying induction, maintenance, and/or loss of tolerance in nonhuman primate (NHP) allograft models of kidney, pancreatic islet, heart, lung, liver, or intestinal transplantation.

Organ transplantation is the preferred treatment for many end-stage organ diseases when other therapies have failed. While one-year graft survival rates now approach or exceed 90% for most organs, long-term graft and patient survival remains sub-optimal for all organ transplants. Immune-mediated graft injury is a leading cause of both short and long-term allograft failure. The current standard of care relies on life-long, non-specific immunosuppressive therapy that, while necessary to protect the allograft from immune injury, is associated with significant morbidity, including toxic side effects that contribute to late graft failure. Advances in induction of immune tolerance to donor organs, cells, or tissue through the development of new therapeutic strategies has the potential to eliminate the need for life-long immunosuppressive therapy, increase long-term graft survival and life expectancy, and improve health-related quality of life. The value of NHP transplant models is due, in large part, to the high degree of similarity between NHPs and humans in terms of physiology and immune system function. Thus, research supported by the NHPCSG paves the way for translation of basic discovery research and design of scientifically sound and ethically acceptable clinical trials in islet and organ transplantation, including regulatory Food and Drug Administration (FDA) approvals.

NIAID is strongly committed to developing safe and efficacious immune tolerance induction regimens that result in enhanced long-term graft survival and reduced morbidity in clinical transplantation. In 1998, NIAID convened an Expert Panel for Research on Immune Tolerance that endorsed the conceptual framework, scope and timeliness of NIAID’s plan to accelerate research in this area. Two subsequent panels, the NIAID Expert Panel on Ethical Issues in Clinical Trials of Transplant Tolerance and the Expert Review Panel for NIAID's Extramural Transplantation Research Program, identified NHP tolerance research as an essential step to provide "...critical data on safety, toxicity and potential efficacy that cannot be obtained ethically in human clinical trials . In response to these recommendations, a research program in NHP models of allogeneic kidney and islet transplantation was established in 1999. In 2004, the program expanded to include research in heart and lung models as well as an Infrastructure and Opportunities Fund. NIAID remains committed to the goals of this program and its direct relevance to the NIH mandate to translate basic discovery research to the clinic. NHPCSG-funded research has provided key supporting data for the design of multiple clinical trials, including several that are ongoing or in development.

Available Nonhuman Primate Resources

• To facilitate NHPCSG research, NIAID supports breeding colonies of specific pathogen-free (SPF) cynomolgus macaques (Macaca fascicularis) and Indian-origin rhesus macaques (Macaca mulatta). NIAID animals are pedigreed and major histocompatibility complex (MHC)-typed to enable rigorous experimental design and data interpretation through knowledge of the degrees of relatedness and MHC disparity or identity between donors and recipients. While NIAID does not guarantee the availability of these animals for NHPCSG-supported studies, research-aged animals are prioritized for use in NHPCSG studies.
• In addition, NIAID supports the NHP Reagent Resource, which develops, produces, and distributes immunologic reagents optimized for use in NHP research, including antibodies for NHP in vitro diagnostics, and immune-modulating reagents for in vivo administration. The NHPCSG has collaborated with the NHP Reagent Resource to develop and/or evaluate numerous reagents that are now in use by the wider researcher community.

The current renewal U19 FOA and companion U01 FOA (RFA-AI-22-002) will support research projects that use NHP models of allogeneic islet, kidney, heart, liver, intestine, or lung transplantation.

While individual approaches may vary significantly, the research objectives must incorporate both of the following:

1) One or more novel tolerogenic approaches

• In vivo safety and efficacy assessment of immune tolerance induction regimens or refinements/modifications of existing regimens in NHP models, including development of immune-modulating agents, if required.

2) Accompanying mechanistic and/or biomarker studies

• Elucidation of the underlying immunologic mechanisms responsible for or contributing to induction, maintenance, loss, and/or lack of immune tolerance achieved by the regimen tested in vivo.
  And/or
• Development, evaluation, and validation of biomarkers or other novel means for predicting or assessing the induction, maintenance, loss, and/or lack of immune tolerance and/or onset of acute or chronic graft rejection.

Additional objectives related to the tolerogenic approach or mechanistic studies may be proposed, such as alternative transplantation sites for pancreatic islets or measures to improve the safety and/or tolerability of the tolerogenic approaches tested, as long as the primary focus of the application meets the above basic requirements.

Milestones

The research plan must include realistic, explicit, and quantitative annual milestones for each proposed project. These milestones will be used by NIAID program staff to assess annual progress and support funding decisions.

In addition to the requirements above, note that:

• Collaborations between NHP transplant model researchers and investigators outside this research community, including relevant basic science immunologists and infectious disease experts, are encouraged.
• Use of new technologies and approaches, including those that are minimally- or non-invasive, is encouraged.
• Because the long-range goals of this FOA are to develop and evaluate candidate tolerogenic approaches for transplantation in humans, opportunities to interact with NIAID-funded clinical trials programs are possible and may include development of and participation in defined preclinical safety and efficacy studies.

Applications proposing the following will be considered non-responsive and will not be reviewed:

• Studies in animal models other than NHPs, unless used solely as an in vivo assay to assess the NHP immune response;
• Human subjects research, although use of human specimens in confirmatory or comparative assays is allowed;
• Clinical trials (all phases);
• Xenotransplantation;
• Preliminary development of an NHP transplantation model (e.g., surgical techniques for reliable post-operative recovery and initial allograft function while on standard immunosuppression);
• Studies with a primary focus on improving isolation, preservation, or supply of organs, tissues, or cells;
• Hematopoietic cell transplantation, unless proposed in the context of islet or organ transplantation (e.g., optimization of bone marrow chimerism approaches for tolerance induction);
• Transplantation of any organs or tissues other than pancreatic islet, kidney, heart, lung, liver, or intestine, unless performed in the context of islet, kidney, heart, lung, liver, or intestinal transplantation (e.g., multivisceral transplantation or thymic tissue transplantation as a means of tolerance induction);
• Studies of non-specific side effects of an immunomodulatory agent (e.g., drowsiness, fatigue, constipation);
• Studies focused on HIV/AIDS-related research.

Applicants are advised to contact the Scientific/Research Contact with any questions they may have regarding the responsiveness of their application.

Administrative Core: The Administrative Core will be responsible for the overall management, communication, coordination and supervision of the program, including monitoring progress, developing and implementing a project management plan with defined timelines.

Scientific Core(s): If proposed, Scientific Cores will support the research projects with technologies and services. A Scientific Core must be used by at least two of the Research Projects.

Infrastructure and Opportunities Fund (IOF) Management Core: To capitalize on emerging opportunities consistent with the goals of the NHPCSG, specified funds will support pilot research projects and their administrative management through the Infrastructure and Opportunities Fund (IOF). Each application is required to submit an IOF Management Plan as part of the IOF Management Core. Post-award, one U01 or U19 (companion RFA-AI-22-002) awardee institution will be selected by NIAID to manage the NHPCSG IOF. Projects recommended for funding by the Steering Committee and approved by the NIAID Project Scientist will be funded as subawards/consortium agreements by the institution selected to manage the IOF.

Research Projects: Each application must contain at least two research projects that should show synergy and be organized around a common central theme and/or overall hypothesis.

Steering Committee

All PDs/PIs and Project Leaders of funded awards will serve on the NHPCSG Steering Committee, whose purpose is to coordinate and facilitate activities of the NHPCSG and promote optimal research flexibility, synergy, and efficiency through collaboration and sharing of reagents, samples, protocols, and experimental results. Steering Committee voting members will include the contact PD/PI from each U01 award and the contact PD/PI and one Project Leader from each U19 award (note: the Project Leader voting member may rotate annually). Non-voting members will include any additional Project Leaders from each U19 award, the non-contact PDs/PIs on multiple PD/PI awards, and the NIAID Project Scientist. Select scientists other than the awardees may serve as non-voting members when additional expertise is required for committee breadth and balance, to be determined by majority vote of the Steering Committee with NIAID approval. Voting members will elect a Chair by majority vote from among non-government Steering Committee members. In addition, the NIAID Project Scientist may appoint up to two external scientists to the Steering Committee as non-voting NIAID advisors. Subcommittees may be established as needed to facilitate the activities of the NHPCSG. Additional responsibilities of the Steering Committee members are described in section VI.2

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)
• U.S. Territory or Possession

Other

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

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

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

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

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

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

• An investigator may be a PD/PI, multiple PD/PI, or U19 Project Leader on ONLY ONE application submitted in response to either RFA-AI-22-002 or RFA-AI-22-003.
• A PD/PI, multiple PD/PI, U19 Project Leader, or U19 Core Leader may serve as a collaborator on another U01 (see companion FOA RFA-AI-22-002) or U19 Project or Core provided there is no scientific overlap between the applications.
• A U19 Core leader, if not the PD/PI or multiple PD/PI of the U19 or U01 or Project Leader of a U19, may serve as a Core Leader on another U19 provided there is no scientific overlap between the applications.
• Multiple PDs/PIs are allowable on the overall application; however, each project or core may have only one U19 Project Leader or Core Leader.

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).

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

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Maggie Morris Fears, Ph.D.

Telephone: 301-761-5444

Email: maggie.morrisfears@nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (use for Scientific Core(s) and Infrastructure and Opportunities Fund Management Core)	6 each
Projects (use for Research Projects)	12 each

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Infrastructure and Opportunity Fund (IOF) Management Core: required; 1
• Scientific Core(s): optional
• Research Projects: required, minimum of 2

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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.

Each PD/PI or multiple PD/PI must commit a minimum of 1.8 person months per year to ensure success of the program.

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

Research Strategy: This narrative section should summarize the overall research strategy for the multicomponent application, including its significance, innovation and approach while highlighting the program's conceptual unity. The multi-component application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another and interactive.

This section should state the problem to be addressed and lay out a broad strategy to resolve it; citing the contributions of the individual projects and core(s) to the overall program goal. To highlight program synergy, applicants should describe how the individual components will coordinate to achieve the overall goals and aims of the Program and how the program as a whole will benefit from any unique cohorts, samples, collaborations, or resources. Include a schematic overview of the interactions and collaborations among the components and list of relevant publications coauthored by members of the Program. Program synergy may also be addressed in other sections of the application, as appropriate. Summarize the special features of the environment(s) and/or resources that strengthen the overall program. Renewal applications should contain a brief description of progress made to date.

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core .

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

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

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

Specific Aims: List in priority order, the broad, long-range objectives and goals of the Administrative Core. State the core's relationship to the Program goals and how it relates to the individual Research Projects and Cores in the application.

Research Strategy: Explain the plans for organizational and administrative management of the overall program, and for coordination and communication within the Program and with the NHPCSG Steering Committee and NIAID project scientist.

Describe approaches for monitoring project progress; use prioritization for any shared resources or scientific cores (if applicable); describe plans for internal quality control of on-going research, management of day-to-day program activities, and management of contractual agreements (if applicable). Describe communication and cooperation among program leaders and/or program investigators. Include a dispute resolution plan.

If data and statistical analyses are components of the Administrative Core, include detailed plans for these activities.

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

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

Appendix:

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

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application 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.

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

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

The IOF Core Budget should include cost break-down and justification for the following:

• IOF Management Leader (0.6 person months maximum)
• IOF administrator (3.0 person months minimum)
• IT staff for website administration (2.0 person months maximum)
• IT computing supplies, if required
• IOF Review Manager
• Total of $200,000 for IOF pilot projects included in the Other Direct Costs category.

Indirect costs for salary, supplies, and administration of pilot project subawards/consortium agreements (assume 2 new subawards per year) should be included in the total 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 the proposed activities and services of the IOF Management Core. Concisely describe how the IOF will function to further the goals of the NHPCSG.

Research Strategy:

The IOF Management Plan should include:

• A clear administrative structure and designated IOF administrator for coordinating activities between the IOF institution and the NIAID Project Scientist, IOF pilot project applicants and awardees, and an awardee-institution's grants management staff;
• A description of administrative procedures designed to ensure:
• 1) timely award of Steering Committee-approved pilot projects via issuance of subawards/consortium agreements, including their establishment, renewal, and compliance with applicable Federal regulations, policies, and guidelines for research involving NHPs (if applicable), 2) accurate monitoring and prompt payment of invoices, and 3) efficient administrative and financial closeout of subawards/consortium agreements after project completion.
• A communications plan for periodic reporting to the NIAID Project Scientist on the status of IOF funds, subawards/consortium agreements awarded, and any requests for changes in the subaward/consortium agreement budget period or project scope.
• Information Technology (IT) support for the development (if needed) and maintenance of a secure, password-protected NHPCSG website for housing NHPCSG-specific documents and for receipt and review of pilot project applications;
• Statement of commitment from the PD/PI to serve as the IOF Management Leader and accept overall fiscal and administrative responsibility for the IOF, if selected by NIAID to receive designated IOF funds.

This section should only include information about the management of the IOF; do NOT include any proposed IOF research projects or plans for scientific review of IOF applications. The NHPCSG Steering Committee will establish guidelines for the solicitation and evaluation of IOF project applications.

Letters of Support: Provide a letter from the PD's/PI's institutional signing official agreeing to take fiscal responsibility for the management of the Infrastructure and Opportunities Fund if chosen by NIAID to administer the funds.

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

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

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application 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.

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

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

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

Specific Aims: List in priority order, the broad, long-range objectives and goals of the Scientific Core. State the Core's relationship to the program goals and how it will contribute to two or more of the individual Research Projects in the application.

Research Strategy: Use this section to describe how the proposed Core activities will contribute to meeting the Program’s goals and objectives. Scientific Core activities may include, but are not limited to, assay performance or other standardized procedures, provision of resources, and/or data management and analyses.

Include a clear and detailed description of the facilities, skills, and/or techniques provided by the Core. Indicate the relevance of the Core to the primary theme of the application. Identify the specific projects to be served by the Core and the interactions of the Core with the Scientific Projects. The activities of the Scientific Core must not overlap with those of a proposed project.

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

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

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

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application 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.

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: Complete this section for each project as you would for an individual grant application. Note: ASSIST screens will show an asterisk for this attachment indicating it is required.

List all performance sites that apply to the specific component.

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

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

Budget forms appropriate for the specific component will be included in the application package , with the following additional instructions, as noted.

Each Project Leader must commit a minimum effort of 1.2 person months per year.

Animal Purchase

NIAID animal resources may be inadequate to meet all research needs of the NHPCSG, therefore include all costs for NHP purchase, assuming they will come from sources other than the NIAID NHP colonies. In the budget justification, note the vendor/supplier and expected animal availability for the proposed studies.

When NHPs are provided from the NIAID colonies, costs for all shipping, handling, and special testing fees will be the responsibility of the awardee. In future years NIAID may implement a cost recovery program for provision of the NIAID animals such that a given award is decreased by the amount budgeted for purchase of NHPs when animals are supplied through the NIAID NHP colonies.

Note that if animals from the NIAID NHP colonies are available for a proposed study, they may not be available for shipment to non-US sites, depending on the country’s import regulations and cost considerations.

Travel

Proposed budgets should include travel costs for the Project Leader and one additional investigator to attend the 1.5 day annual NHPCSG Steering Committee Meeting in Rockville, MD.

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

Specific Aims: List in priority order the broad, long-range objectives and goals of the proposed Project. Concisely describe the specific hypothesis or hypotheses to be tested. Note the individual Project's relationship to the Program’s goals and how it relates to other projects or cores.

Research Strategy: Use this section to summarize how the proposed research will contribute to meeting the Program’s goals and objectives. Explain the significance of the research, innovation involved and rational for the approaches proposed (i.e., how will they help you accomplish your specific aims). Interactions with other projects and the scientific cores should be described.

The application must include at least one tolerogenic approach as well as mechanistic and/or biomarker studies that may be incorporated as either a separate aim or as integral parts of the study aims.

In addition to a detailed Vertebrate Animal Section, the Research Strategy should provide a description of, and rationale for, the acquisition and preparation methods used for procuring donor organs, tissues, or cells used for the studies and the sources, methods, and numbers of donor and recipient samplings/biopsies proposed.

Provide a justification for the numbers of animals used per experiment, with a discussion of power calculations and statistical considerations of the proposed experiments within the bounds of limited resources and budgetary constraints. Describe conclusions that can be drawn using the specified number of animals proposed

Treatment Protocols, Objectives, and Yearly Milestones

• Clearly define experimental endpoints and provide a rationale for the proposed tolerance approach and relevance to human transplantation.
• Include a synopsis and treatment diagram/timeline detailing the proposed treatment protocol(s).
• State interim and long-term objectives and include realistic, explicit, and quantitative annual milestones and detailed timeline identifying critical decision points where a revised approach may be necessary.

Letters of Support:

Reagent Source(s)

Provide letters of commitment from reagent sources, where appropriate, documenting the availability, quantity, and anticipated timelines for supply of key reagents.

Non-NIAID Animal Source(s)

Provide letters verifying animal availability from other sources should the NIAID NHP colonies not be able to fully meet the application's NHP requirements or needs.

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

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

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the program 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 program 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 program that by its nature is not innovative may be essential to advance a field.

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

Specific to this FOA: Would the Program, as proposed, advance transplantation tolerance research? What is the likelihood that the results of the proposed studies will contribute to new approaches and knowledge that will inform future studies in NHP models and/or human transplantation? Is the Program as a whole scientifically compelling? Will coordination and synergy between the individual research projects and cores advance the central objectives of the U19? Will the integration of the individual projects into a single Program have added benefits relative to the pursuit of each project independently?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the program? 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?

Specific to this FOA: For applications designated multiple PDs/PIs, is the Leadership Plan both adequate and appropriate to ensure sufficient coordination and communication among the PDs/PIs? Do(es) the PD(s)/PI(s) commit at least the minimum level of effort to ensure efficient coordination between projects and overall Program success? Do(es) the PD(s)/PI(s) have the necessary scientific and leadership abilities to actualize an integrated and focused research program?

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?

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

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

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

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

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

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

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

Significance

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

Specific to this FOA: Would the project, as proposed, advance transplantation tolerance research? What is the likelihood that the results of the proposed studies will contribute to new approaches and knowledge that will inform future studies in NHP models and/or human transplantation?

Investigator(s)

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?

Specific to this FOA: Is the proposed commitment and level of effort of the Project Lead sufficient to ensure the success of the project? Are the expertise and level of effort of those with NHP transplantation experience and basic transplantation investigators and/or immunologists appropriate to the work proposed?

Innovation

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

Approach

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

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

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

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

Specific to this FOA: Will the critical resources, reagents or therapeutics needed be available for the study within the proposed time-frame? Are the proposed tolerogenic approaches appropriate and ready for NHP research? Are approaches to study underlying mechanisms and/or biomarkers appropriate? Are the yearly milestones and timelines adequate, appropriate, and reasonably attainable?

Is the justification for the numbers of animals reasonable? Are the statistical considerations for the proposed experiments and the proposed conclusions that may be reached appropriate? Are the acquisition and preparation of the solid organs, tissues or cells to be used in the studies and the proposed methods, source, and number of NHP samplings/biopsies appropriate?

Environment

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

Specific to this FOA: Are appropriate and sufficient animal housing and care facilities available to the investigators to perform the studies proposed?

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

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

• Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?
• Is the management plan for fiscal accountability, contractual agreements, and communication within the program appropriate?
• Are the plans for coordination, communication, problem identification and resolution, and the establishment of a strong, collaborative U19 environment appropriate?
• Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?
• Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate?

• Is inclusion of the scientific core well-justified in terms of the contributions anticipated for the individual Research Projects? Does the core support at least two research projects?
• Is the relationship of the scientific core to the Program s central focus strong?
• Are the strategy, methodology, and analyses proposed well-reasoned, feasible, and appropriate to accomplish the specific aims of the core, if applicable? Are potential problems, alternative strategies, and benchmarks for success presented, if applicable?
• Are the quality of the relevant facilities or resources provided and criteria for prioritization and usage appropriate?
• Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate?

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

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

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

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

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

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

Not Applicable

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

Not Applicable

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

Infrastructure and Opportunities Fund (IOF) Management Core

Does the plan provide a clear administrative structure with a designated IOF administrator and IT support to enable adequate organization, communication, and budgetary oversight? Are the personnel charged with managing the IOF appropriate? Based on the above considerations, Reviewers will comment on whether the IOF Management Plan is acceptable or unacceptable.

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.
• Progress made under any current NHPCSG award, if applicable.
• Availability of critical reagents and resources.

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

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 2 CFR Part 200, 45 CFR Parts 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:

• Determining and coordinating the scientific and administrative activities of the approved projects; setting project goals and timelines; accepting and implementing common guidelines approved by the Steering Committee;
• Serving as a voting member on the Steering Committee; participating in Steering Committee activities, and accepting and implementing the policies and procedures developed by majority vote of the Steering Committee;
• Working closely with NIAID staff in the scientific, technical, and administrative management of this program;
• Ensuring that all NHPs obtained from the NIAID breeding colonies are used only for the expressed purposes of the individual Cooperative Agreements funded under this FOA or the projects funded under the NHPCSG IOF RFA as recommended by the Steering Committee and approved by NIAID.
• Ensuring that all IOF awards adhere to the rules and guidelines established by the NHPCSG Steering Committee.
• Timely submission of manuscripts for publication that are (co)authored by members of the award and supported in part or in total by the NHPCSG and for adherence to all aspects of the collaborative group s Publications Policy, to be determined by the NHPCSG Steering Committee and NIAID.
• Making new information and materials, including research samples, tools, methods, reagents, and data developed under these awards known and available to the broader research community and members of this program through publications, presentations, web announcements, submission to public resources or databases, and reports to NIAID and/or the NHPCSG Steering Committee.

Note: Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

A program official from the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) will serve as the NIAID Project Scientist for this program. The role of the Project Scientist will be to facilitate and not to direct NHPCSG activities. The Project Scientist will:

• Serve as a non-voting member(s) of the Steering Committee and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies. It is anticipated that the majority of Steering Committee decisions will be reached by consensus and NIAID staff will be given the opportunity to offer input into this process, but the manner of reaching this consensus and the primary decision-making responsibility will rest with the Steering Committee, except where stated in this FOA.
• Assist the Steering Committee Chair and subcommittee chairs in scheduling meetings of the NHPCSG Steering Committee and subcommittees and actively participate in agenda development as well as the organization and planning of a NHPCSG-hosted workshop.
• Support project activities through technical assistance, advice, and coordination;
• Advise in the selection of sources or resources (e.g., determining where a particular reagent may be found) and identification of potential collaborations to further the goals of the NHPCSG;
• Coordinate NIH staff assistance and serve as a resource for scientific and policy information related to the goals of the awardee s research;
• Approve distribution of NHPs from the NIAID breeding colonies for individual research projects, based on overall availability and number of animals proposed in the peer-reviewed studies.
• Review milestones prior to award and during the course of the project period, and request revised milestones, as needed.
• Annually review progress towards achieving the goals of the project and previously agreed upon milestones to ensure successful completion of the project.
• Approve redirection of research aims within the scope of the original award during the funding period, as needed. NIAID reserves the right to terminate or curtail a study/project in the event of a substantial failure to meet study milestones or other major deviation from the approved project's aims.

Note: A program official from the NIAID/DAIT will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The NIAID Project Scientist and the PD(s)/PI(s) will coordinate the scientific objectives and progress made on individual awards to facilitate the achievement of program goals. This may include pre-approved redirection of research aims within the scope of the original award, as needed, to ensure consistent progress.

The NIAID Project Scientist and the PD(s)/PI(s) will collaborate to revise project milestones prior to initial or annual awards, based on peer review of the originally proposed milestones and/or the PD(s)/PI(s) and/or the NIAID Project Scientist assessment of the proposed yearly milestones.

Steering Committee:

The Steering Committee will:

• Meet at least annually, but more often as needed, to carry-out its role as the main governing board for the NHPCSG;
• Identify and advise the NIAID Project Scientist on scientific opportunities, emerging needs, and impediments to overall program success;
• Develop a publications policy, including guidelines for publication of collaborative project results;
• Coordinate timely preparation and provision of annual reports, if requested;
• Provide guidance and recommendations to investigators regarding study design and implementation;
• Advise the NIAID Project Scientist on ways to maximize the value of the NIAID NHP breeding colonies.
• Oversee the general activities of NHPCSG IOF by providing recommendations for: 1) the procedures, policies, and subcommittees required for the solicitation, receipt, review, and evaluation of feasibility, pilot, resource development, or collaborative projects; 2) approving, disapproving, or discontinuing funding for individual IOF projects; and 3) website functionalities and resources to facilitate the goals of the NHPCSG.
• Outline an Action Plan that includes the organization of at least one workshop to be held during the funding period. The workshop should include participants from outside the NHPCSG to ensure consistent engagement with the broader research community and to advance the broader goals of the NHPCSG through collaboration-building and the education of the next generation of transplant investigators.
• If requested by the NIAID Project Scientist, the NHPCSG Steering Committee or a designated subcommittee will prepare a cumulative group progress report or ad hoc reports, as required, on NHPCSG activities, potentially including a summary of ongoing and newly-initiated studies (including any funded IOF projects); manuscripts published, in press, and in preparation; presentations given at regional, national, and international meetings; other notable NHPCSG endeavors; and future plans to be submitted at a time agreed upon by the NIAID Project Collaborator(s) and the Steering Committee Chair.

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.

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Julia Shaw, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3711
Email: julia.shaw@nih.gov

Maggie Morris Fears, Ph.D
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444
Email: maggie.morrisfears@nih.gov

Caleb Waller
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6643
Email: caleb.waller@nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.