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

The purpose of this Funding Opportunity Announcement (FOA) is to support novel strategies for the rational design of vaccines against hepatitis C virus (HCV), to assess the vaccines for their ability to induce protective immune responses, and to select candidates for preclinical development and clinical testing. To this end, it will be critical to advance knowledge of the structural basis for broad immunological protection, and to elucidate correlates of HCV protection by leveraging samples from existing human cohorts and vaccine studies. This information will serve as a guide for the construction of new and improved candidate prophylactic HCV vaccines that will be assessed for immunogenicity and efficacy in appropriate animal models.

Hepatitis C (HCV) infection leads to chronic persistence of the virus in 70-80 percent of individuals, often leading to serious, progressive fatal liver diseases cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Acute infection with HCV is largely asymptomatic and, while 20-30 percent of people spontaneously clear infection, clearance of initial infection does not prevent reinfection. An estimated 71 million people world-wide are chronically infected with HCV, with as many as 50 percent unaware of their infection status, including in the U.S., where over 2 million people are chronically infected with HCV and often co-infected with HIV. In the U.S, the ongoing opioid epidemic has contributed to a recent increase in HCV infection rate by more than 200 percent, mostly in the age group of 15-24 years.

Treatment of chronic HCV infection has been revolutionized by several new directly acting antiviral (DAA) drugs, which are safe and highly effective, achieving a sustained viral response (SVR) in > 95% of all treated patients. Despite the promise of these new treatments, the burden of chronic HCV disease remains high. Unfortunately, HCV therapeutic cure does not prevent reinfection or eliminate residual cancer risk. Furthermore, the cost of treatment remains prohibitive, and access to treatment is poor particularly in resource challenged areas, where the burden of disease is also the highest. Mounting evidence suggests that DAA failure can lead to the evolution of drug-resistant virus. The FDA recently warned of rare instances of serious liver injury or failure with certain hepatitis C treatments in some patients with advanced liver disease. Thus, even the best treatment options are not enough to eradicate HCV. Finally, there is a lack of universal screening for HCV and consequently the infection is under-diagnosed. This makes control of the HCV pandemic extremely challenging. Recent studies show that, in most countries surveyed, new infections outpace treatment and cure, setting back the World Health Organization (WHO) goal to eliminate HCV by 2030. Taken together, there is a clear and urgent need for a preventative vaccine against HCV.

Developing a vaccine against HCV will be challenging for a multitude of reasons. One major hurdle is the extreme sequence diversity of the HCV genome, as represented by multiple genotypes and subtypes. In fact, HCV exhibits higher genetic variability than HIV, and the rapid accumulation of mutations during HCV replication can lead to the generation of virus quasi-species that enable continual escape from immune surveillance, usually leading to virus persistence. Nevertheless, spontaneous clearance of HCV infection does occur in a significant proportion of infected individuals, indicating that protective immunity can be naturally induced, although it is unclear which immune responses correlate with clearance.

Examination of immune responses in people who have spontaneously cleared HCV following infection shows that they develop broadly neutralizing antibodies (bNAbs), as well as HCV-specific CD4+ and CD8+ T cells. bNAbs appear early post infection, with only minimal somatic hypermutation. The major targets for neutralizing antibodies and bNAbs are the surface glycoproteins of HCV, E1 and E2, which are proposed to exist as heterodimers E1E2 on the surface of HCV virions. HCV entry and infection are mediated by the binding of E1E2 and E2 to several receptors on the surface of hepatocytes, including CD81, to which the HCV E2 protein has been shown to bind. While the crystal structure of E2 has been extensively studied, the structure of the E1E2 heterodimer remains to be elucidated. The heterodimer is conformationally flexible, complicating structural analysis, as well as being heavily glycosylated, with certain glycan residues potentially masking critical neutralizing epitopes. While epitope mapping studies have revealed several clusters of overlapping epitopes on both E2 and the E1E2 heterodimer, it has not been possible to obtain a complete map of the relevant bNAb epitopes without detailed analysis of the E1E2 native structure.

Traditional approaches to developing an HCV vaccine have been evaluated and met with limited success. An experimental vaccine comprising heterodimerized, recombinant E1E2 plus a potent adjuvant has been evaluated in both animals and humans. This vaccine protected chimpanzees against challenge with homologous virus, and in a phase I trial [ClinicalTrials.gov identifier NCT00500747], antibodies were elicited in vaccinated subjects against several epitopes on E1E2; in a few cases these antibodies could cross-neutralize several major HCV genotypes. Additional development will be necessary to optimize the breadth of the humoral responses.

There is also strong association between robust T cell responses and HCV clearance. Both in chimpanzees and humans HCV-specific CD4 and CD8 T cell responses are associated with the eradication of viremia, and these responses can be elicited by a vaccine containing HCV nonstructural proteins that carry several T-cell epitopes. Recently, a phase II trial [NCT01436357] of a vaccine designed to elicit T-cell responses against HCV structural proteins, NS3-NS5 was completed. Disappointingly, this vaccine neither prevented HCV infection nor chronic progression, despite the induction of CD8 T-cell responses in most of the subjects. Likely causes for the failure of this vaccine are potential mismatches between the vaccine induced HCV-specific responses and the infecting virus, or the inadequacy of these responses to eliminate infected cells. Further evaluation of these samples and analysis of the data obtained from this trial and from acute and chronic HCV cohorts that spontaneously clear virus, should yield clues to defining protective immunity and will be critical to the design of new vaccines.

The problems of high sequence diversity and viral quasi-species are also encountered in the development of vaccines against HIV. A recent innovation in that arena is the in silico design of mosaic antigens, assembled from natural HIV proteins by computational optimization based on sequences from multiple, globally disparate, HIV strains, for the creation of new HIV vaccines. A vaccine consisting of a bivalent cocktail of mosaic antigens comprising HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus, and boosted by synthetic proteins, elicited significantly enhanced B and T cell responses in rhesus macaques and humans. A phase III trial (NCT03964415), is in progress to test a tetravalent mosaic vaccine with an aluminum phosphate adjuvant in thousands of high-risk subjects in the US, Latin America and Europe for protective efficacy against HIV infection.

Research Objectives and Scope

An optimal HCV vaccine should induce potent and broadly cross-reactive neutralizing antibodies against HCV envelope components and virus-specific T-cell responses. The rational design of a vaccine for HCV, will require isolation of bNAbs and determination of their cognate linear or conformational epitopes. In addition to the design of immunogens, the choice of delivery platforms and adjuvants is critical. Mice, guinea pigs and chimpanzees have been used for assessing the generation of immune responses and their protective ability, but currently none of the existing models can reliably predict immune responses or clinical outcomes in humans.

The purpose of this funding opportunity announcement (FOA) is to support novel strategies for the rational design of vaccines directed against hepatitis C. To this end, it will be critical to elucidate the structural basis for broad immunological protection, and to study vaccine induced immune responses in human subjects from previous clinical trials. This information could serve as a guide for the construction of new and improved candidate prophylactic HCV vaccines and their evaluation for immunogenicity and efficacy in appropriate animal models. Investigators within the program should have prior experience that demonstrates their ability to carry out rational design of vaccines and a demonstrated ability to conduct relevant translational studies to assess them. Potential areas of research include, but are not limited to, the following:

• Advance knowledge of the structural basis for broad immunological protection.
• Isolate bNAbs from infected cohorts, and/or map bNAb protective epitopes on the surface of the virus
• Elucidate the native structure of the E1E2 heterodimer
• Introduce vaccine-stabilizing mutations on E1E2 heterodimer, as necessary, while preserving bNAb epitopes
• Minimize distracting or non-neutralizing epitopes that could result in antibody-mediated interference of the protective broadly neutralizing antibody response
• Elucidate correlates of HCV protection by leveraging samples from existing human cohorts and vaccine studies.
• Evaluate samples from people who spontaneously clear HCV infection for clues to protective immunity
• Understand the immunological and virologic outcomes of prior vaccine trials, as such data could guide the design of future vaccine strategies
• Select/design HCV T-cell novel epitopes using computational tools to choose and optimize HCV genome sequences that would elicit cross reactivity against multiple genotypes
• Construct prototype vaccines and evaluate their immunogenicity.
• Combine novel antibody and T-cell vaccine approaches and strategies (vectors, adjuvants, etc.) that will lead to both potent and durable antibody responses, as well as sustained HCV-specific CD4 and CD8 responses.
• Develop new animal models to conduct pertinent translational studies to evaluate immunogenicity and correlates of protection.

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

• Applications that focus on HIV/SIV/AIDS
• Clinical trials

Program Components

This research program will consist of an Administrative Core, Scientific Cores, and at least two Research Projects.

Administrative Core: The Administrative Core will be responsible for managing, coordinating, monitoring overall progress, and supervising the entire range of the program's activities.

Scientific Core(s): A Scientific Core (at least 1 scientific core is required, but not more than 2) could provide shared support services to the Research Projects, such as monoclonal antibody production, peptide and/or nucleic acid syntheses, immunology laboratory services, sequencing, structural biology and bioinformatics laboratories, statistical support, animal core, and, if necessary, a clinical core that will provide clinical samples.

Research Projects: Each research program should propose at least two complementary and related Research Projects to advance the design and construction of HCV vaccine candidate(s) towards further preclinical and clinical development.

Annual Programmatic Meetings: Annual Programmatic Meetings will be held to facilitate communication and collaboration among funded research programs.

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)

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

Applicant Organizations

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.

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:

Frank De Silva, Ph.D.
Telephone: 240-669-5023
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	6 pages
Core (use for Scientific Core[s])	6 pages each
Project (use for Research Projects)	12 pages each

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: Required, maximum of 1
• Scientific Core(s): 1 Scientific Core required, maximum of 2
• Research Projects: Required, minimum of 2, no maximum

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.

Within the biosketches, present evidence of the investigators prior experience that demonstrates their ability to carry out rational design of vaccines and to conduct relevant translational studies to assess them. Document how the PD/PIs possess the leadership, scientific ability, and managerial experience required to develop, manage, and direct an integrated and focused program.

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: List in priority order, the broad, long-range objectives and goals of the proposed research program. Concisely describe the hypothesis or hypotheses to be tested. Outline a clear plan for a rational vaccine design as well as define novel strategies and approaches to achieve enhanced immunogenicity against HCV.

Research Strategy: Summarize the overarching theme of the proposed program. The multi-component, multi-disciplinary application should be viewed as a confederation of interrelated Cores and Research Projects, each capable of standing on its own merit, and complementary to one another. This section should provide the conceptual rationale of the program and lay out a broad strategy for accomplishing the stated goals. When describing the program, each Core and Research Project should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. A visual representation of the interactions amongst the components and complementary scientific endeavors can delineate the collaborative and synergistic potential of the proposed program. Discuss the cohesiveness of the program, and how the Research Projects and Cores relate to a single common theme demonstrating multidisciplinary interactions, coordination, and synergy. Discuss how the scientific gains and synergy achieved by combining the projects into a multi-project program are superior to the gains achievable if each project were pursued independently.

Discuss how the proposed program proposes novel strategies to elicit broadly protective neutralizing antibodies and improve upon existing T cell approaches.

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.
• For institutions/organizations proposing a single PD/PI, the PD/PI must serve as the Administrative Core Director. For institutions/organizations proposing multiple PD(s)/PI(s), the Contact PD/PI must serve as the Administrative Core Director.
• Provide details regarding the experience of the Administrative Core Director to illustrate his/her qualifications to manage the overall program.

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

Meetings: In Year 01, include funds in the budget for the PD(s)/PI(s), collaborators, key personnel to travel to, and attend a kickoff meeting, to be held shortly after the award over 1 full day in the Bethesda, MD area. Beginning in Year 02 include funds in the budget for an annual program meeting to be held over two full days in the Bethesda, MD area. Do not include costs associated with organizing and holding the kickoff or annual program meetings.

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

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Administrative Core.

Research Strategy: Describe plans and procedures for establishing and managing an Administrative Core that provides the organizational capacity to ensure the following:

• Coordinating, supervising, identifying and resolving problems, and managing all research program activities, which includes sponsoring activities to advance the research program’s integration.
• Providing a supportive structure sufficient to ensure the accomplishment of all research program goals.
• Assisting Core and Research Project Leaders with administrative aspects of their projects, such as gathering of annual progress reports and facilitating other communications with awardees and their mentors.
• Promoting collaboration and coordination among Core and Research Project Leaders.
• Fostering outreach activities to promote collaborations with the pertinent scientific communities.
• Communicating with other awarded research programs regarding collaboration and coordination of activities and projects.
• Communicating and interacting with the NIAID Project Scientist, Program Officer, or other staff.

Management Plan: Include a Management Plan that describes the organization of the proposed research program and its management structure to facilitate achievement of the objectives of the proposed program. Include a plan for fiscal accountability and communication within the Program.

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

• 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, 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 (Scientific 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 (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific 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) (Scientific 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 (Scientific 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 (Scientific Core)

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.

PHS 398 Research Plan (Scientific Core)

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core.

Research Strategy: Describe how the proposed Core activities will contribute to meeting the research program's goals and objectives and explain the rationale for selecting the general methods and approaches to accomplish the Core activities.

Indicate the relevance of the Core to the primary theme of the application and provide justification for the Core to support at least two Research Projects effectively. Applications that propose Cores must give a clear description of the facilities, techniques, and skills that the Core will provide to the Research Projects. Cores should not be duplicative of other services or facilities available to the program investigators. Examples of services that might be provided by a Core include, but are not limited to, structure determination, sequencing and bioinformatics support, monoclonal antibody production, peptide and/or nucleic acid synthesis, immunologic evaluation, statistical support, animal core, and a clinical core that will provide clinical samples.

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 (Scientific Core)

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, 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.

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, in priority order, the broad long-term goals and specific objectives of the proposed Research Project. Concisely describe the hypothesis or hypotheses to be tested. In addition, state the Research Project’s relationship to the research program’s goals and how they relate to other Cores or Research Projects in the application.

Research Strategy: Describe how the proposed project will contribute to meeting the program’s overall goals and explain the rationale for selecting the methods to accomplish the Specific Aims. State the biological significance of the research and indicate the project's relevance to the primary theme of the 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:

• 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 (Research Projects)

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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).

• Does the application have a clearly defined and scientifically justified theme?
• Are the overall Program goals significant and focused on studies that increase knowledge of an important area relevant to the design of vaccines against HCV?
• Are the goals of each of the Research Projects and Cores significant and scientifically compelling?
• Is the program as a whole cohesive and do the Research Projects and Cores relate to a single common theme demonstrating multidisciplinary interactions, coordination, and synergy?
• Are the scientific gains and synergy achieved by combining the projects into a multi-project program beyond the gains achievable if each project were pursued independently?
• Do the PD/PIs have the leadership, scientific ability, and managerial experience required to develop, manage, and direct an integrated and focused program?

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.

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: Does the proposed program outline novel strategies to elicit broadly protective neutralizing antibodies and improve upon existing T cell approaches?

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: Do the investigators have appropriate prior experience in rational design of vaccines and demonstrated ability to conduct relevant translational studies to assess them?

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 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 projectinvolves 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).

Administrative Core

• Is the administrative and organizational structure appropriate and adequate to achieve the goals of the proposed program?
• Is the Management Plan appropriate to facilitate achievement of the objectives of the proposed program?
• Is the Management Plan for fiscal accountability and communication within the program appropriate?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Are plans for facilitating communication between the projects appropriate?
• Are the experience and level of commitment of the Administrative Core Director adequate to manage the overall program?

Scientific Core(s)

• Are the proposed Scientific Core(s) sufficiently justified and relevant to the theme of the overall program?
• Is adequate justification provided that each Scientific Core will support at least two Research Projects and that services will be used effectively?
• Are the facilities or services provided by the Scientific Core(s) of high quality?
• Are the Scientific Core(s), Leader(s) and other personnel well qualified with an adequate commitment of time?

As applicable for the program/projects 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 program 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

Not Applicable

Not Applicable

As applicable for the program/projects 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.

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

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee 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, 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. 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 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:

• Overseeing, managing, and coordinating the Research Projects and Cores within the overall research program;
• Ensuring that the individual projects and Cores are synergized to advance the goals of the research program;
• Retaining primary responsibility for the planning, directing, and executing the proposed scientific activities;
• Keeping the NIAID Program Official apprised of any potential impediments to execution of the goals of any one Research Project or Core;
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

The role of the NIAID Project Scientist (PS) in the cooperative agreement is to support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PD(s)/PI(s).

• The PS will work closely with the PD(s)/PI(s) to facilitate collaborations and to leverage the resources available to the research program;
• The PS will monitor the progress of the research program, help coordinate research approaches, and contribute to the shaping of research projects or approaches as warranted. The PS will support and facilitate this process but will not direct it;
• The PS will keep the program informed about other ongoing studies supported by NIAID to avoid duplication of effort and encourage sharing/collaboration in infectious diseases research. The PS will coordinate access to other NIAID resources, as well as assist the research efforts by facilitating access to fiscal and intellectual resources provided by industry, private foundations, NIH intramural scientists and other federal government agencies as appropriate;
• The PS will assist in the determination of the site for the Annual Programmatic Meeting; and
• The PS will coordinate the conference calls with PD(s)/PI(s), as needed.
• Additionally, an NIAID Program Official 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 (PS) and the PD(s)/PI(s) will coordinate to facilitate the achievement of program goals.

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 Executive 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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Rajen Koshy, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3294
Email: [email protected]

L. Jean Patterson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4830
Email: [email protected]

Frank De Silva, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5023
Email: [email protected]

Shaun Gratton
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3594
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.