Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Anti-retroviral therapy (ART) can suppress HIV replication to levels below detection by standard assays but does not completely eliminate residual viral reservoirsand must be taken for life. Despite many years of ART this persistent HIV reservoir  causes most people living with HIV (PLWH) to experience viral rebound within weeks after treatment interruption. The persistence of the virus in PLWH on ART also supports a chronic status of immune activation and inflammation that could explain an increased risk of developing non-AIDS co-morbidities such as metabolic syndrome and cardiovascular diseases.

Over 16 years ago hematopoietic stem cell or bone marrow transplant with allogeneic cells  from a donor with a homozygous mutation in the HIV coreceptor gene, CCR5Δ32/Δ32, provided the proof-of-concept that HIV could be cured by cell therapy. Since then, additional examples of HIV cure have been reported in the literature;  most after transplantation with CCR5Δ32/Δ32 allogeneic hematopoietic stem cells.  While stem cell transplantation shows promise and provides clues for an HIV cure, stem cell transplant procedures have significant safety risks and cannot be a routine approach for people who do not need them to treat life-threatening cancer or other blood and immune system diseases. The intensive and costly procedure is not feasible for most PLWH, including those in low-resource settings.

Recent advances in genome editing technologies, cell therapies, and novel delivery strategies are effectively treating some genetic diseases and cancers, with multiple strategies being evaluated in clinical trials and a few being approved for clinical use. There are new genome  editor tools ( CRISPR-Cas variants, designer nucleases and recombinases, base editors and prime editors, RNA editing, epigenomic editors)  with distinctive mechanisms, increased on-target efficacy and lower off-target effects. Efficient and programmable viral and non-viral systems are being developed to deliver genes and genome editing machinery to specific  cell(s), tissue types, and/or organs. Next-generation cell-based immunotherapies have been  engineered for improved persistence, target cell recognition, and minimal side-effects. Optimization, simplification and automation of cell culturing and manufacturing processprovides increased efficiency, scalability, and cost effectiveness while retaining consistency and quality of product specifications.  These emerging innovations in cell and gene therapy approaches, technologies for cell engineering and new strategies for product manufacturing can be applied to target underlying HIV-associated viral and immune pathologies, reconstitute protective immunity, and achieve viral suppression or elimination of the persistent HIV reservoir.

Research Objective and Scope

The goal of this notice of funding opportunity (NOFO) is to support integrated multi-project research programs to apply emerging and improved technologies , alone or in combination, to the development of innovative gene- and/or cell-based  HIV cure approaches, defined as either sustained viral remission in the absence of antiretroviral treatment or elimination of HIV infection from the body. Applicants  should leverage recent insights into virus-host interactions, genotype and phenotype of HIV latent cells, and reservoir  cell survival and proliferation. Private sector partnerships are required to facilitate development of strategies appropriate for clinical studies and ultimately commercialization, if proven to be safe and effective.

In keeping with the focus on a treatment strategy, applications are required to include a plan for an INTERACT (Initial Targeted Engagement for Regulatory Advice on CBER Products https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otat-interact-meeting) meeting with the FDA early in product development and by the end of the second year of support. This meeting with the FDA will offer preliminary informal feedback about the appropriate design and conduct of preclinical test-of-concept studies and the development of the approach.

Partnerships:

Applications must include a collaborative partnership that includes the private sector. The term “private sector” comprises large and small organizations, domestic and foreign organizations, nonprofit and for-profit organizations. Examples of private sector partners appropriate to this NOFO include, but are not limited to, biotechnology, pharmaceutical, bioengineering, stem cell, and chemical companies. The private sector partner(s) must contribute intellectually to the overall goals and objectives of the program, contribute expertise and/or resources needed for planning and implementation of translational development for the purpose of FDA licensure and commercialization of therapeutics, and have a record of past successes moving concepts to practical applications.

Milestones:

The application must provide a Milestone Plan and identify significant research outcomes, with timelines, to reflect planning and management of the overall integrated Program. The milestones should be criteria for evaluating the progress and direction of the Program and not a restatement of the specific aims.  Plans for an INTERACT meeting (Initial Targeted Engagement for Regulatory Advice on CBER Products https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otat-interact-meeting) with the FDA should be included in the Milestone Plan. Milestones will be negotiated prior to award and may be renegotiated during the project period.

Scientific Advisory Board:

A Scientific Advisory Board (SAB) of outside experts recommended by recipients and approved by NIAID will be constituted after award to review progress and make recommendations to investigators. Do not contact, recruit, or name potential SAB members prior to completion of review activities. Recipients will be required to attend an annual meeting with NIH staff and the Scientific Advisory Board (SAB). The purpose of the meeting is to review progress, discuss problems encountered, planning of future research activities, and establish priorities in following years.

Annual Meetings:

The Administrative Core will coordinate an annual meeting for all Key Personnel, the Scientific Advisory Board (SAB) and NIAID staff to review goals and milestones achieved during the year, problems encountered, and external events that may influence the direction of work in following years. It is expected that the SAB members will attend annual meetings sponsored by the grantee to assist with interpretation of results and planning of future studies, and to assess progress during the course of the project.

Research goals and objectives include but are not limited to:

• Strategies to apply advanced novel genome engineering technologies to target HIV provirus DNA or RNA: to excise, inactivate, or silence the expression of the integrated viral genome or modulate gene expression and protein function.
• Cell- or tissue-targeting methods to enable in vivo delivery of gene therapies.
• Development of allogeneic or universal “off the shelf” cell and gene therapeutics.
• Approaches to modulate immune responses that impact therapeutic efficacy and dosing, including methods to reduce immunogenicity of delivery vectors and/or transgenes, avoidance of pre-existing immunity, or minimize elicitation of anti-drug antibodies.
• Ex vivo or in vivo gene modification to render cells resistant to infection and/or enhance the immune system's ability to suppress viral expression or to eliminate HIV- infected cells. Examples of cell sources include but are not limited to autologous or allogeneic cell sources such as T and B cells, NK cells, blood stem or progenitor cells, and induced pluripotent stem cells (iPSCs).
• Novel methods to enhance transplantation and engraftment, or minimize rejection, of modified cells as part of an HIV-targeted transplantation strategy. Some examples include bioengineering strategies or manufacturing process innovations to optimize cell recovery and viability, maintenance of desired cell state and function, in vivo cell survival, differentiation, or localization and retention at relevant tissue sites.
• Test-of-concept studies in appropriate animal models, including non-human primates. These studies could include efficacy studies in small animals on suppressive antiretroviral therapy, assessment of safety, immunogenicity, and resistance development.

NIMH will co-fund applications which contain Research Projects or Scientific Cores of interest to their mission. Examples of areas of interest to the NIMH include, but are not limited to, the following:

• Targeting of gene- or cell-based therapies to compartments of the CNS that harbor latent or persistent HIV.
• Efficacy and/or toxicity of gene- or cell-based therapies in CNS compartments, as explored in test-of-concept studies in animals or human samples.

Overall Program Structure

Research Programs funded under this NOFO will be comprised of multiple components. These are:

Administrative Core

This core will provide the management, coordination, and supervision of both the scientific and fiscal aspects of the overall program.

Scientific Cores (Optional)

An application may propose one or more Scientific Core(s) to provide resources and/or facilities that are essential for the activities of two or more Research Projects.

Research Projects

Each application must include a minimum of three interrelated individual Research Projects. Each Research Project must be integrated in the Program overall.

Additional Information

Applicants are encouraged to leverage existing resources to help support the needs of the program whenever possible. Examples of government-funded resources include, but are not limited to:

• Centers for AIDS Research (CFAR, NIAID);
• Human Tissue and Organ Research Resource (HTORR, NIAID);
• Clinical and Translational Science Awards (CTSA, NCATS);
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG, NIAID);
• Catalyze Program (NHLBI);
• Resources Access for Preclinical Integrated Drug Development (RAPIDD) Program (X01) (NIAID)

Early consultation prior to application submission with relevant NIH institute Scientific/Research staff is strongly recommended. If requested by the applicants, staff can advise whether the proposed Program meets the goals of this NOFO and discuss responsiveness questions. During the consultation phase, if the proposed Program does not meet the programmatic needs of this NOFO applicants will be strongly encouraged to consider other Funding Opportunities.

Applications proposing research in the areas listed below will be considered non-responsive and will not be reviewed:

• Vaccines
• CCR5 as the sole target. Combination therapeutic strategies that include CCR5 gene disruption in T-cells or hematopoietic stem cells are acceptable
• Transplantation research that is not an integral part of the HIV cure approach being developed under the NOFO
• Applications that focus exclusively on HIV infection in the central nervous system or neuro-AIDS
• IND-enabling studies, i.e., pharm/tox, GLP validation studies
• Clinical trials. However, use of existing clinical samples is permitted

Additionally, applications that do not include the following will be considered non-responsive and will not be reviewed.

• A private sector partner
• A Milestone Plan
• A plan for an INTERACT meeting with the FDA in the Milestone Plan
• The required number of projects

Encouraging Broad Participation

Every facet of the United States scientific research enterprise—from basic laboratory research to clinical and translational research to policy formation–requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. NIH encourages applicants to recruit prospective researchers from diverse backgrounds, including individuals from underrepresented groups, to build a diverse pool of candidates for potential participation in their research programs (see NOT-OD-20-031, Notice of NIH’s Interest in Diversity and NOT-OD-22-019, Reminder: Notice of NIH’s Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities).

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• 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 Organization) are not 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 How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

3. Additional Information on Eligibility

Number of Applications

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 per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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 NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

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:
Bruce Sundstrom, Ph.D.
Telephone: 240-669-5045
Email: sundstromj@niaid.nih.gov

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- 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
• Scientific Core: optional, maximum 3, each Core must support as least two Research Projects
• Research Projects: required, minimum 3, maximum 4

Overall Component

When preparing the application, use Component Type ‘Overall’.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

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.

Research and Related Senior/Key Person Profile (Overall)

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

Budget (Overall)

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.

PHS 398 Research Plan (Overall)

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

Research Strategy: Within the Research Strategy provide a concise summary of the overall research plan for the multi-research project application, describe the scientific challenges and opportunities being addressed, the integration of the research projects and scientific core resource (if applicable) components, and why these components are essential for accomplishing the overarching goals of the Program. Describe how individual research projects and scientific core(s) are collaborative and related to a common theme, with each research project addressing an aspect of the overall program. Describe how each research project is well integrated into the overall program and form a synergistic, scientifically compelling whole. Demonstrate the conceptual wholeness of the overall program by stating the general problem area, laying out a broad strategy and timeline for the research goals, and provide a compelling argument for the team-research approach. Explain the synergy between Research Projects and Scientific Cores. Summarize the special features in the environment and/or resources that make this application strong or unique.

Discuss how the proposed gene- and/or cell-based strategy represents an improvement over other anti-HIV therapeutic strategies and the pathway to either long-term remission in the absence of antiretroviral treatment or elimination of HIV-1. If the strategy is designed to effect long-term remission, discuss the possible duration of virus suppression expected and how often the treatment would need to be given. If combination studies are proposed, provide a rationale for choosing the modality(ies) to be combined with the gene- and/or cell-based therapy.

Within the Overall Research Plan provide a description of the following:

• Goals, relevant background, significance, and a description of the impact of the science proposed in relation to the state-of-the-art of the field. Include an explanation of how the work proposed is innovative and incorporates current and emerging technologies or methodologies in gene and cell-based therapeutic development. Describe how the research represents a significant improvement to current anti-HIV therapeutic strategies.
• An explanation of how the goals of the program will advance the development of genetic and cell based therapeutics for an HIV cure strategy, i.e. a strategy that can achieve either long-term remission in the absence of antiretroviral treatment or elimination of HIV-1. If the strategy is designed to effect long-term remission, discuss the possible duration of virus suppression expected and how often the treatment would need to be given.  If combination studies are proposed, provide a rationale for choosing the modality(ies) to be combined with the gene- and/or cell-based therapy.  
• Explain the contributions of each component in the context of the whole program.  Include a graphic illustrating the relationship of the various research projects and scientific cores to one another and their place in the overall program.
• Describe the private sector partner involvement, the expertise and resources it provides, and how it will be integrated into and benefit the proposed program.
• Provide a Milestone Plan and identify significant research outcomes, with timelines, to allow assessment of the program's progress toward its stated goals throughout the program period. Milestones must not be simply a restatement of the specific aims. Include the INTERACT meeting with the FDA by the end of the second year of grant award. Prior to funding an application, the Program Official will contact the applicant to discuss and negotiate milestones.
• Explain the assembly of the team of investigators to achieve the goals of the proposed research. Describe the leadership and scientific capabilities of the PD(s)/PI(s), and the overall scientific and technical expertise of the research team and organization to effectively design and conduct the proposed activities.

Letters of Support: A letter of support should be included to document institutional support for the Program and should address laboratory, animal and office space, equipment, administrative resources. PD(s)/PI(s) are encouraged to provide letters of support from private sector partners regarding their participation in the Program, and plans for intellectual property, data sharing, and other legal matters that may arise during the period of the award.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - 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 How to Apply - 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 How to Apply - 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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the How to Apply- Application Guide must be followed.

Administrative Core

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Administrative 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 (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

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

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

Include expenses for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications related to the program, and communication expenses.

Include necessary expenses for the planning, implementation, and administration of the data management and sharing plan (DMSP).

Include expenses related to the travel of Scientific Advisory Board (SAB) members, the Program PD/PI, and key personnel to the annual meeting of the awardees in the Administrative Core budget. Assume travel for two unnamed SAB members and P01 key personnel to attend a 1-day face-to-face meeting per annum 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.

PHS 398 Research Plan (Administrative Core)

Specific Aims: List in priority order, the objectives and goals of the proposed Core. In addition, state the Core's relationship to the Program's goals and how it relates to the individual Research Projects or other Scientific Cores in the application.   

Research Strategy: As part of the Administrative Core, provide a Management Plan that includes a description of the organizational structure and roles of administrative staff, including the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated. Provide plans for coordination among the Research Projects and Scientific Cores and program including presentation, publication and NIH reporting requirements for data generated by the overall and individual research projects, tracking of research project and scientific core progress, and intellectual property management; problem identification and resolution and a contingency plan for replacing the PD/PI(s), if needed. Describe how the Administrative Core will establish and maintain a strong collaborative environment for the Program. When applicable, describe interactions with resources and/or programs not directly supported by this award and how these resources and/or programs would be leveraged to support the program.

Scientific Advisory Board (SAB): The SAB will be constituted after award from recommendations put forward from recipients in consultation with the Program Officer. Describe the internal procedures that will be developed for responding to recommendations from the Scientific Advisory Board (SAB). Do not name, recruit or contact potential SAB members prior to award or in the application.

Letters of Support: Include Letters of support, if applicable

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.

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 (Administrative 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.

Scientific Core(s)

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Scientific Core(s))

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(s))

Enter Human Embryonic Stem Cells in each relevant component.

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

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(s))

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(s))

• 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(s))

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(s))

Specific Aims: List in priority order, the broad overarching long-range objectives and goals of the proposed Scientific Core. In addition, state the Core's relevance to the Program's goals and how it relates to the individual Research Projects or other Scientific Cores in the application.

Research Strategy: Describe how the proposed core activities will contribute to meeting the goals and objectives of the research proposed in the application and indicate the specific two or more Research Projects that it will support. Explain the rationale for the general methods and approaches proposed to accomplish the specific aims. Include details of the facilities, resources, and professional skills provided and explain how requests for services will be prioritized and coordinated.

Letters of Support:  Include letters of support, if applicable

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.

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(s))

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.

Research Projects

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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-range objectives, and goals of the proposed Research Project. Describe the hypothesis or hypotheses to be tested. In addition, state the Research Project's relationship to the Program's goals and how it relates to the individual Research Projects or other Scientific Cores in the application.

Research Strategy: Use this section to describe how the proposed Research Project activities will contribute to the Program goals and objectives and explain the rationale for the general methods and approaches proposed.  In addition, describe the relevance of the Research Project to the primary theme of the application. Describe the research design, methodologies, and analyses to be used to carry out the specific aims.  Describe any novel concepts, approaches, or tools to be utilized.

Letters of Support: Include letters of support, if applicable

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.

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.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. 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

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer 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 form. 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 unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in How to Apply - 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.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to 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 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 NOFO: How well do the Program goals advance the development of genetic and cell based therapeutics for an HIV cure strategy? To what degree is the Program as a whole scientifically compelling? To what extent is the integration of the individual Research Projects into a single Program more beneficial than pursuing each project independently?

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 NOFO: To what extent does the scientific and technical team including the private sector involvement anticipate and incorporate the range of expertise required to conduct the proposed activities in a collaborative and integrated effort? 

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?

Specific to this NOFO: To what extent does the Program propose an innovative strategy that incorporates current and emerging technologies or methodologies in gene and cell-based therapeutic development? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the 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 NOFO: To what degree are the Projects and Core(s) (if proposed) integrated and synergistic, such that they will interact and inform each other in ways not possible as separate research project grants, and at an economy of scale? To what extent does the approach address the specific challenges of advancing the development of genetic and cell based therapeutics for an HIV cure strategy, i.e., a strategy that can achieve either long-term remission in the absence of antiretroviral treatment or elimination of HIV-1?

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?

Overall Impact - Administrative and Scientific Core(s)

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

Administrative Core

• How appropriate and adequate to the attainment of the objective(s) of the proposed Program are the administrative and organizational structure?
• To what extent are the management plan for fiscal accountability and communication within the Program justified?
• How well developed are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the Program?
• To what degree are the experience, level of commitment, and availability of the Administrative Core Leader and staff adequate to manage the Program?

Scientific Core(s) (if applicable)

• To what extent is the provision and Core services for the individual Research Projects critical and justified?
• How well justified is the relationship of a Scientific Core to the central focus of the overall Program?
• To what degree is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate?
• How appropriate are the qualifications, competence, and commitment of the Core Leader and key personnel?

Overall Impact – Individual Research Projects

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).

Scored Review Criteria - Individual Research Projects

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?

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?

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?

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?

Additional Review Criteria - Overall, Cores and Research Projects

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

Protections for Human Subjects

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall, Cores, and Research Projects

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

Milestones: To what extent do the proposed Milestones describe significant research outcomes and timelines to enable clear assessment of the program's progress toward its stated goals?  

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

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 policies and practices, 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 will receive a written critique.

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.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their 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 Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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 recipient 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, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

If a recipient receives and award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH 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 NOFO.

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 System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, 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 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

When multiple years are involved, recipients 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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to  2 CFR Part 200, 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 (Responsibility/Qualification in SAM.gov, formerly 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 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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: https://www.era.nih.gov/need-help  (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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Betty Poon, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID) 
Telephone: 240-669-5024
Email: poonb@mail.nih.gov 

Lisbeth A Welniak, PhD
National Heart, Lung, and Blood Institute (NHLBI) 
Phone: 301-827-8297
E-mail: welniakla@nhlbi.nih.gov

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3869
Email:jjeymoha@mail.nih.gov

Bruce Sundstrom, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5045
Email: sundstromj@niaid.nih.gov 

Joshua Elesinmogun 
National Institute of Allergy and Infectious Diseases (NIAID) 
Telephone: 301-761-7928
Email: elesinmogunjs@nih.gov 

Lynn M Rundhaugen
NHLBI - NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Phone: 301-480-4546
E-mail: lr235y@nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email:siscor@mail.nih.gov

Section VIII. Other Information

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 2 CFR Part 200.