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 instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

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.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



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

In 2023, an estimated 39.9 million people globally were living with HIV, there were 1.3 million people who acquired HIV, and 630,000 people died from AIDS-related illnesses worldwide (World Health Organization [WHO]). Among people living with HIV (PLWH), morbidity and mortality is increasingly driven by co-infections. The risk of tuberculosis (TB) progressing from latent to active disease is estimated to be up to 20 times greater in PLWH than among those without HIV, with fatality rates of 16-35%. For HIV-associated hepatitis, WHO estimates that 2.6 million PLWH are also living with Hepatitis B Virus (HBV) and 2.75 million are also living with Hepatitis C Virus (HCV) worldwide.

Given the burden of life-long HIV treatment regimens and need for prevention modalities with longer windows of protection and/or less frequent administration, long-acting/sustained release (LA/SR) antiretrovirals represent a major therapeutic advancement for PLWH. Through maintaining consistent and effective drug levels for extended periods of time and providing effective drug concentrations at reduced drug dosing intervals, LA/SRs are able to significantly simplify dosing requirements, enhance convenience, improve adherence, and have the potential to reduce emergence of drug resistance and conceivably lower the associated costs of healthcare overall. Therefore, support for Investigational New Drug (IND)-enabling pre-clinical activities to rapidly advance lead LA/SR formulations to clinical trials is needed.

Since PLWH are frequently also living with TB, HBV, or HCV, administration of LA/SR antiretrovirals will likely require concurrent treatment for these infections. Thus, the development of LA/SR strategies for TB, HBV, and HCV will be essential to reduce burden of these diseases on PLWH by:

• shortening regimens for TB prevention and treatment, currently associated with months of daily pill intake, which will likely increase completion rates of prescribed TB drug regimens and reduce the burden of TB disease;
• providing compatible treatment options for both HIV and HBV coinfection to simplify treatment regimens; and
• offering a one-shot cure for HCV that will ultimately help to eradicate HCV.

Research Objectives and Scope

NIAID-funded biomedical research has led to the discovery of novel and promising LA/SR approaches to treat HIV and HIV-associated TB, HBV, and HCV and prevent HIV. Many of these technologies require investment to conduct the necessary translational development work for advancement towards an IND filing and clinical trials. The purpose of this notice of funding opportunity (NOFO) is to support the requisite IND-enabling preclinical activities to accelerate the transition of lead candidates from research and development (R&D) to IND and subsequent clinical testing.

For the purposes of this NOFO, applications are sought for LA/SR technologies that have shown a strong rationale and competitive advantage for further development and demonstrated feasibility and effectiveness in appropriate non-clinical or animal models at intermittent dosing from either a single administration (such as injection, topical, oral administration) or continuous dosing regimen (implant, transdermal patch, etc.) with a minimum dosing interval of once every three months for HIV treatment or prevention or a minimum of once-a-month treatment for TB, HBV or HCV. Strong rationale and competitive advantage are defined as product attributes that may include, but are not limited to:

1. A demonstrated window of protection for treatment or prevention of HIV and/or HIV associated co-infections greater than those products that are currently in clinical testing.
2. Clinical studies or other evidence of improved acceptance, adherence, or compliance than currently available products or those in clinical testing.
3. Products with new chemical entities (NCEs) or new pro-drug approaches that enable the minimal targeted dosing intervals outlined above.
4. Multipurpose prevention technologies (MPTs) defined as HIV treatment or prevention strategies coupled to other anti-microbicides for associated co-infections, and/or hormonal and non-hormonal contraceptives and/or hormone-replacement therapy for post-menopausal women.
5. In-Vitro In-Vivo Correlation (IVIVC) data for product dissolution/release and/or accelerated stability, and/or physiologically based pharmacokinetic (PBPK) modeling that meets guidance recommendations for inclusion in regulatory dossiers.
6. Efficient scaleup processes and supply chain, technological advancements for manufacture, storage, and transportation conditions of quality products.
7. Cost effectiveness in low and middle-income countries (LMICs).
8. Post-approval considerations including implementation, commercialization strategies or life-cycle planning including engagement of appropriate hand-off partners.

Proposed LA/SR technologies may include small molecules, peptides, proteins, oligonucleotides, gene therapies, polymers, and contain a single or a combination of Active Pharmaceutical Ingredients (APIs) or be used in combination with other agents, such as transporters, enzyme inhibitors, or immunomodulators, to improve their efficacy and prolong therapeutic effect.

Proposed product development activities may include, but are not limited to:

• IND-directed pharmacology and toxicology studies to address regulatory requirements for clinical safety, toxicity, and drug dosing parameters. These studies may also include in vitro and/or in-silico models responsive to appropriate Food and Drug Administration (FDA) guidance documents and the FDA modernization Act
• Evaluation of genotoxicity, reproductive toxicity, or carcinogenicity
• Advanced in vivo studies to confirm the therapeutic window, thresholds of protection, or evaluate drug combinations for establishing appropriate clinical dosing regimens
• Process development and scaleup production of a batch for animal studies
• Good Manufacturing Practices (GMP) manufacturing
• Stability testing program based on FDA guidance
• Regulatory activities, including pre-IND meetings with FDA
• Non-clinical studies of clinical-stage products

Research Plan Requirements

Applicants must include (1) a Target Product Profile (TPP) to summarize long-acting drug product critical properties and targets for development, (2) a defined IND-directed product development strategy in concordance with FDA guidance that addresses all IND components, (3) description of ownership and Intellectual Property (IP) rights for the proposed product to ensure freedom to operate, (4) a plan for a pre-IND meeting with the FDA by the end of the fourth year of funding, and (5) a timeline. Applicants are expected to define critical points within the timeline and establish a set of benchmarks throughout the entire program to monitor progress and to stay focused on program objectives towards filing the IND application.

Industry Partnerships and Collaborations

To develop and implement product development strategy and activities, applicants are required to identify an industry partner or translational advisor with an established record in product development and potential collaborators and/or consultants with specialized expertise that might include Contract Research Organizations (CROs), Chemistry, Manufacturing and Controls (CMC) experts, business and regulatory professionals, patent attorneys and clinical investigators to bridge the preclinical and clinical development activities.

Expert Advisory Board (EAB)

An Expert Advisory Board (EAB) consisting of independent experts in the areas of research and product development is required. Members of the board will be identified soon after award to provide guidance and strategic insights and make recommendations based on their specialized knowledge and experience to ensure scientific rigor of the program and progress towards the set goals.

Phased Innovation Awards

Due to the high-risk, high-impact nature of the research and the milestone-driven preclinical development activities, this funding opportunity will use the R61/R33 Exploratory/Developmental Phased award with investigator-provided milestones. Proposed milestones will be reviewed and negotiated prior to award.

Support will be provided for up to two (2) years for the R61 phase to obtain critical research and preclinical data to further demonstrate the feasibility and competitive advantages of proposed technologies. Up to three (3) years of support may follow for the R33 phase to enable preclinical development with potential for IND submission.

Milestones:

• Applicants are required to include milestones for the R61 phase that will be negotiated with NIH staff prior to the award.   The milestones proposed in the application must be objective, quantifiable, rigorously defined, feasible (in terms of the study timeline and approach), and scientifically justified.
• Milestones that are a restatement of application Specific Aims do not meet the definition of milestones for this NOFO. Examples of milestones might include: establishing a therapeutic window in vivo, defining an optimal dosing regimen including pharmacokinetic (PK) lag and tail, demonstration of feasibility and reproducibility to fabricate and manufacture targeted product.
• Fulfillment of R61 milestones will define criteria for success and consideration for transition to R33 funding.

R61 to R33 Transition:

• Before the end of the R61 phase, recipients will submit the R61/R33 transition package describing advancement toward the negotiated milestones and justifying continuation with the originally proposed R33 studies. These materials will be evaluated by NIH Program staff.
• Transition to the R33 phase is neither automatic nor guaranteed. The R33 funding decisions will be based on the original R61/R33 peer review recommendations, overall progress, successful completion of negotiated milestones for the R61 phase, demonstrated strong potential for translation to clinical trials, programmatic priorities, and availability of funds. It is expected that approximately half of the projects supported during the R61 Phase will continue into the R33 Phase.

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

• Discovery and early product development work.
• LA/SR technologies for HIV and HIV-associated co-infections that do not meet the minimum dosing interval requirements as defined in the NOFO.
• Development of broadly neutralizing antibodies (bnAbs), non-neutralizing antibodies, bispecific or trispecific antibodies, or other engineered antibody-based approaches (e.g., molecules combining antibody domains with other non-antibody domains, such as CD4) as long-acting agents.
• Single agent prevention modalities that include advancement of Tenofovir or cabotegravir, including pro-drugs.
• Strategies for HIV, TB, HBV or HCV vaccines for treatment or prevention, or PrEP strategies coupled to a vaccine.
• Clinical trials are not allowed, but use of samples from clinical trials supported elsewhere is allowed.
• Applications lacking the following:
  
  • Target Product Profile (TPP)
  • Defined IND-directed product development strategy
  • Description of ownership and Intellectual Property (IP) rights for the proposed product
  • Timeline and/or Gantt Chart
  • Inclusion of an industry partner or translational advisor
  • Plans for an External Advisory Board (EAB)
  • Milestones for the R61 phase
  • Clearly articulated plans for a pre-IND meeting

Applicants are encouraged to contact the Scientific/Research Contact(s) located at the end of this NOFO to discuss planned strategies for developing an application.

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 Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 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 the 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 registrations; 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 their 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 Definition 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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Shiv A. Prasad, Ph.D.
Telephone: 240-627-3219
Email: [email protected] 

Page Limitations

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

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Briefly describe in clearly demarked sections the overall objective(s) and specific aims for both the R61 and R33 phases of the proposed research plan. 

Research Strategy: Describe the market opportunity and potential impact of the proposed LA/SR strategy on treatment for HIV, TB, HBV, or HCV, or on prevention of HIV. Detail competitive advantages and the end-user acceptability of the proposed product. Describe any end-user, caregiver or healthcare professional studies done that informed product design or Target Product Profile (TPP) parameters.

Describe the LA/SR platform and the physical, chemical, and biological features of product(s) in development. Summarize existing research data and the effectiveness in appropriate non-clinical or animal models at intermittent dosing from either a single administration (such as injection, topical, oral administration) or continuous dosing regimen (implant, transdermal patch, etc.) that demonstrate the effective concentrations and feasibility of a minimum dosing interval (required treatment duration or window of protection) of once every three months for HIV treatment or prevention or a minimum of once-a-month treatment for TB, HBV, or HCV.  Describe the rationale, competitive advantage, and feasibility of the proposed LA/SR approach to enable development of the next generation of safe, effective, and end-user-acceptable products for HIV and HIV associated co-infections.

Target Product Profile (TPP, required): In a clearly labeled section applicants must provide a TPP to describe a summary of critical properties, optimal and minimally acceptable attributes, and targets for development of a new LA/SR product.  Product attributes may include, but are not limited to, product release profile and duration of action, optimal dosing regimen, acceptable duration of pharmacokinetic (PK) lag periods and tails, maximum and minimum PK targets, PD targets, stability and storage requirements, desirable physical properties, and cold chain/storage requirements.

IND-Directed Product Development Strategy (required): Define the IND-directed product development strategy in concordance with FDA guidance and address all IND components, specifically product indication, route of administration and dosing, Chemistry, Manufacturing and Controls (CMC) strategy, pharmacology and toxicology assessments and a clinical program outline that will facilitate submission of an IND application and clinical trials of the investigational LA/SR product. In addressing the requirements of an IND application:

• Include product indication, route of administration and dosing.
• Provide sufficient details to describe preclinical studies in appropriate models to characterize the therapeutic effect, pharmacological, drug dosing and safety parameters, and to establish the No Observed Adverse Effect Level (NOAEL) using proper controls and statistical power. Describe how the results will be integrated and used to guide candidate development. Include plans to evaluate genotoxicity, carcinogenicity, and any special toxicity tests related to the drug's particular mode of administration or conditions of use, per FDA guidance.
• Describe scalability of the processes and availability of materials to ensure reproducibility of the LA/SR technology and the safety, identity, quality, purity, and strength of the investigational product. Include plans for scale-up activities, GMP manufacturing, development of quality control methods, and stability testing program based on FDA guidance.
• Outline the expected clinical program to ensure that the preclinical strategy is aligned with the potential design of the clinical trials and enables safety assessment of the drug candidate in human subjects.
• Describe the regulatory strategy, anticipated regulatory meetings with the FDA, and planned regulatory submissions including dossiers.
• Include defined critical points and a set of benchmarks throughout the entire program to monitor progress and to stay focused on program objectives towards filing the IND application.

Intellectual Property Rights (required): Provide the description of the ownership and the IP position for the product being developed (e.g., patent filed, intentions to file, license acquired from IP owner, etc.) to ensure freedom to operate and ability to share data for both drug and drug delivery system components, including polymers and excipients, as appropriate. Include supporting documentation.

Milestones (required): In a clearly labeled section entitled "Milestones," provide a clear description of the R61 phase milestones that, if met, will justify proceeding to the R33 phase. A milestone is defined as a scheduled event in the project timeline that signifies completion of a major project stage/activity and is not a restatement of the Specific Aim. Within the proposed milestones address critical points of the product development program and describe research outcomes by providing quantifiable measures for success and referring to relevant information to support the rationale. Include clear statements describing how each milestone, if successfully achieved, will support critical parameters and allow advancement of subsequent work that is contingent upon completion of the milestone.

Plans for Pre-IND Meeting (required): Provide the strategy to collect the necessary data and assemble the required package for a pre-IND meeting with the FDA during the R33 Phase. Include within the plan the required pre-IND meeting with the FDA by the end of the fourth year of funding. Describe how the meeting will contribute to product development and enable clinical trials. Having such a meeting with the FDA will increase the likelihood of program success by addressing concerns earlier in the process and facilitate clinical translation.

Timelines and/or Gantt charts (required): In a clearly labeled section, provide the descriptive timelines for proposed activities using a Gantt chart (or equivalent) to illustrate the project schedule, the timeline for each task, and the relationships between individual tasks in the product development program. Include within the timelines/Gantt chart elements the defined critical points and benchmarks from the IND-directed product development strategy for monitoring progress on program objectives towards filing the IND application.

Industry Partnerships and Collaborations (required): In a clearly labeled section, describe the role of each stakeholder, including the required industry partner or translational advisor with an established record in product development, in terms of scientific input and involvement in the strategic planning and activities, and the resources that they will provide to the program to fulfil a critical role in the development team. Describe the process for managing these partnerships and quality oversight.

Expert Advisory Board (EAB, required): In a clearly labeled section, describe plans to identify members of the board based on their specialized knowledge and experience to ensure scientific rigor of the program and progress towards the set goals. Do not name, contact, or recruit any external advisors prior to the completion of application review and funding activities. 

Letters of Support: 

Applications should include Letters of Support from organizations and collaborators demonstrating their involvement and commitment to provide specific services, resources, and expertise to the program.

An industry partner or translational advisor with an established record in product development is required and should be documented by provision of a Letter of Support.

Applicants proposing research involving drugs that are protected by intellectual property, are required to include a Letter from a patent or license holder in support of the proposed research.

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 Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

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

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

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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). 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 the 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.

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

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) 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. See Section III of this NOFO for information on registration requirements.

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 the 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 by the National Institute of Allergy and Infectious Diseases (NIAID), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

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 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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

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 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 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. 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 the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

3. Anticipated Announcement and Award Dates

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 Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an 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.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

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.

4. Reporting

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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. 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.

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: [email protected] (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: [email protected]

HIV Prevention
Kristen A. Porter, Ph.D. 
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7022
Email: [email protected] 

Treatment of HIV, TB, HBV, HCV
Marina N. Protopopova, Ph.D. 
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7653
Email: [email protected] 

Shiv A. Prasad, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3219
Email: [email protected] 

Mark Hodor
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5712
Email: [email protected] 

Fabiola Chacon
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7938
Email: [email protected]  

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.