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 SF424 (R&R) 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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The utility and technical advantages of synthetic nucleic acid platforms (SNAP), including their efficacy, safety, speed of development, and ease of vaccine manufacture, were revealed during the COVID-19 pandemic, thus instilling hope that these technologies can be leveraged for the development of an effective HIV vaccine and broadly neutralizing antibody (bNAb) delivery.  As of now, more than 100 DNA- and RNA-based vaccines have advanced to clinical development for SARS-CoV-2, HIV, other infectious diseases, and cancers. In addition, numerous best-in-class native and engineered bNAbs and their derivatives are in clinical development. SNAP might also provide a means to persistently deliver prophylactic or therapeutic levels of antibodies or antibody derivatives, thereby supplying affordable, timely and sustainable global access to these HIV interventions.

The development of highly effective prevention and treatment strategies for HIV has been a significant scientific achievement over the past 25 years. The introduction of antiretroviral therapy (ART) for HIV treatment and antiretroviral drugs for pre-exposure prophylaxis (PrEP), including long-acting formulations, has changed the trajectory of the HIV epidemic. People with HIV (PWH) who adhere to ART regimens can expect relatively normal life spans and cannot sexually transmit HIV.

Despite these advances, there are substantial barriers to HIV diagnosis, access to care, and adherence to ART regimens, particularly in low and middle-income countries, as evidenced by persistently high rates of new infections and HIV-related morbidity and mortality. Thus, an HIV vaccine, long-acting ART, and ART-free sustained HIV remission (cure) remain essential components of an integrated strategy to end the epidemic. There will be unique requirements for a prophylactic vaccine that blocks HIV infection versus a therapeutic one that sustainably suppresses viral loads in PWH. Developing an effective prophylactic or therapeutic vaccine has proven to be extraordinarily difficult, and there are no licensed vaccines for HIV. 

BNAbs are being explored as both HIV prevention and treatment modalities. The recently completed Antibody Mediated Prevention (AMP) trials demonstrated that infusion of a bNAb can protect humans from HIV infection, provided the virus was sensitive to the administered bNAb. Treatment trials have likewise demonstrated that viral loads can be sustainably suppressed by mixtures of bNAbs in PWH, provided the HIV reservoirs are sensitive to the administered bNAbs. Next generation bNAbs have been engineered for optimized neutralization breadth, effector function properties, and longer half-lives in vivo. Optimized antibody cocktails and engineered bNAbs are in development and based upon clinical trial results, have a good probability of success in HIV prevention and treatment. 

The delivery of HIV vaccines and bNAbs as SNAP has the potential capacity to revolutionize HIV prevention and treatment. SNAP vaccines and therapeutics have excellent safety profiles and product candidates can be translated rapidly from preclinical to clinical evaluation. As such, they offer the potential to increase the speed of iterative product development and testing while reducing cost. However, the extensive diversity and mutability of HIV, along with its capacity to evade immune surveillance and establish long-lived reservoirs, creates unique challenges. Although HIV vaccine antigens and bNAbs and their derivatives still need to be optimized and selected, SNAP are attractive delivery technologies because they can accommodate diverse and multiple inserts for broad coverage. In addition, RNA platforms have been produced in a variety of forms, including self- and trans-amplifying RNAs, and circular RNAs. Exploration of these systems has revealed a diversity of immune-stimulating phenotypes that could be tuned for desirable responses (e.g., stimulation of follicular helper T cells (TFH), induction of cytotoxic T-cell responses, or lack of immunogenicity when expressing bNAbs). These mRNA platforms have also shown, when delivered by lipid nanoparticle (LNP), to be self-adjuvanted, immunogenic, and efficient at inducing substantial TFH to support germinal centers for the development of memory and plasma cells. Importantly, SNAP vaccines enable precise antigen design and the generation of complex proteins in situ with a native-like presentation (e.g., membrane-bound with human glycosylation patterns). Additionally, use of SNAP for vaccines and bNAb could circumvent challenges associated with the costly large-scale production and characterization of traditional protein manufacturing and allow for efficient delivery of immunogen or antibody mixtures that may exhibit improved efficacy. This Notice of Funding Opportunity (NOFO) requires a translational partner with product development expertise to address the considerable manufacturing challenges.

Although less work has been done for SNAP delivery of bNAbs, they can be expressed in humans via Adeno-associated virus (AAV) vectors. For widespread use of SNAP bNAbs, it will be imperative to attain physiologically relevant titers for sustained periods.

Given their versatility and clinical potential, coupled with their proven capacity for rapid product development, there is an urgency to capitalize on the experiences and lessons learned from SNAP technologies and translate them to HIV prevention, treatment, and cure.

Research Objectives

The purpose of this milestone driven NOFO is to advance SNAP for the rapid development and iterative testing of prophylactic and therapeutic vaccines, and for the delivery of bNAbs and bNAb derivatives for HIV prevention, treatment, and cure.

This initiative will evaluate the extent to which DNA/RNA technologies can 1) be applied to various types of HIV vaccine immunogens and complex regimens; 2) elicit stronger, broader, and longer-lasting HIV-specific immune responses; 3) be used in combination with other platforms; and 4) support the delivery of bNAbs or bNAb derivatives for the prevention, treatment, or cure of HIV.

The inclusion of a translational partner(s) as a significant collaborator in the application is required to strengthen the likelihood of successful clinical translation. A translational partner is broadly defined as an individual, group, or unit from a for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical company that is large or small, domestic, or foreign, with an established successful record in product development. Collaboration is defined as a substantial commitment of one or more resources to the project including, but not limited to: research and development plan support and/or guidance, ancillary or related funding, product development support and/or guidance, personnel, provision, and testing in animal or other laboratory models for evaluation, data management resources and/or regulatory support. Inclusion of a commercial regulatory advisory group or consultants from outside the applicant’s organization to assist in preparation of a pre-IND package meets this requirement. Industry applicants are not required to involve collaborators from academic and/or non-profit research organizations, but are encouraged to do so, where appropriate.

Under this NOFO, clinical trials are not allowed but the use of samples from clinical trials supported by other funding mechanisms is encouraged. Animal research is allowed, including the use of small animal models and nonhuman primates with HIV, SIV, or SHIV challenges. It will also be crucial to apply newly developed immunological tools to expand our understanding of the immune response to vaccination at the molecular level and overcome existing challenges to the quality and durability of T-cell and antibody responses to HIV as well as the ability of SNAP to deliver physiologically relevant titers of bNAbs for sustained periods.

Examples of in scope research include, but are not limited to, the use of SNAP to:

• Define molecular, cellular, and systemic events after immunization to inform vaccine design including studies of the characteristics of innate and antigen-specific immune responses and omics signatures using samples from animal studies and/or clinical trials.
• Optimize vaccination regimens including sequential strategies, routes of administration, doses, and immunization intervals for durable responses.
• Evaluate strategies for the expression of proteins stabilized for optimal immunogenic conformations or antigenic epitope display.
• Develop polyvalent, multi-antigen, or mosaic vaccines for broad coverage of HIV strains and subtypes.
• Explore strategies to simultaneously induce neutralizing antibody and CD8 T-cell responses targeting conserved/consensus regions of HIV.
• Evaluate SNAP in combination with other platforms (recombinant proteins, viral vectors, etc.) to improve and prolong the elicitation of desired immune responses.
• Investigate co-delivery of nucleic acid-encoded immunogens and adjuvants or immunomodulatory molecules or mAbs.
• Develop platforms to deliver single and multiple bNAbs and bNAb derivatives for HIV prevention, treatment, and/or cure.
• Explore targeted delivery of vaccines or bNAb molecules to specific cell types and tissues.

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

• Use of synthetic platforms that are not nucleic acid based.
• Studies of host cells transfected and/or transduced ex vivo followed by reinfusion.
• Non-HIV-related research and pure platform improvements.
• Delivery of bNAbs or vaccine via viral vectors.
• Clinical trials.
• Applications without a milestone section.
• Applications without a translational partner(s).

Phased Innovation Awards

Due to the high-risk, high-impact nature of the research, this funding opportunity will use the R61/R33 phased innovation grant award mechanism. Support will be provided for up to three years (R61 phase) for hypothesis-driven design, optimization, and characterization of SNAP for the delivery of synthetic nucleic acid immunogens, bNAbs, and/or bNAb derivatives. Up to two years of support may follow (R33 phase) for additional activities as appropriate, such as evaluation in relevant animal models, but also the evaluation of their developability as products. Proposed milestones will be reviewed and negotiated prior to award.

Before the end of the R61 phase, awardees will submit the R33 transition package, which includes a detailed progress report describing advancement toward the initial milestones and a description of how the completed work justifies continuation with the originally proposed R33 studies. These materials will be evaluated by NIH Program staff; grants selected for continued funding will be transitioned to an R33 award without the need to submit a new application. Transition to the R33 phase is neither automatic nor guaranteed; R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, Program priorities, and availability of funds. It is expected that approximately one-half of the projects supported during the R61 Phase will continue into the R33 Phase. 

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 Government

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant Organizations

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

• 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 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.

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

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

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 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 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 SF424 (R&R) 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:

Barry Margulies, PhD
Telephone: 240-552-1324
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

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

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

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

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

R&R Budget

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

R&R Subaward Budget

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

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

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

Research Strategy:  Provide a brief overview of the research plan, sufficient background information to support the feasibility of the approach that will lead to successful completion of the project and describe how its achievements provide an advancement in a useful prophylactic or therapeutic application. Relevant information may include, for example, pertinent scientific literature, scientific discoveries in other fields that would also propel the HIV field, breakthroughs in methodological or technical barriers to advance SNAP applications or other inferential data that establish the potential for research success. Describe how this work differs from previous approaches and provide the unique features of the proposed work. Propose a research strategy with clearly defined methods and criteria to evaluate success. Describe the overall objectives, studies designed to achieve desirable characteristics of the vaccines and bNAb molecules and strategies to guide the selection of candidate products.

For vaccines:

• Briefly describe the HIV-1 vaccine unmet need(s) and the rationale for using the proposed approach to address the unmet need(s) for the development of a vaccine to prevent acquisition of HIV-1 infection or to sustainably suppress viral loads in PWH.
• If the proposed approach/rationale relies on research in fields outside the current HIV vaccinology (e.g., other infectious diseases, cancer, autoimmune disorders, etc.), the applicant should discuss their relevance to the proposed approach and how progress in these fields enables the proposed strategy.

For bNAb molecule(s):

• Briefly discuss the rationale for choosing a specific bNAb(s) as a candidate to be developed.
• Include the rationale and plans to (1) synthesize or modify candidate molecules and/or construct formulations, (2) conduct non-clinical evaluations such as safety, efficacy, PK/PD, drug-drug interactions, tissue penetration, and (3) address the development of drug resistance.
• In a clearly labeled section applicants should include a summary of critical properties, optimal and minimally acceptable attributes, and targets for development of a new product. (Applicants may provide this information in the format of a Target Product Profile or in another format.)

Applicants must submit a single application that includes both the R61 and R33 phases.

Relevant information or data to support the rationale/hypothesis should be provided as evidence that the proposed project is feasible and well-designed for the intended purpose.

For each phase (R61, R33), describe the planned research approach and explain how this approach will enable the successful achievement of the aims. Do not repeat information or experimental details in the R33 section that are already described in the R61 section. Discuss how the unique composition of the research team will ensure successful completion of the project.

Milestones (required):  Applicants should provide milestones for BOTH the R61 and R33 phases of the award within the research strategy. Applications without a milestone section will be considered non-responsive and will not be reviewed. Within this section, describe the suitability of the chosen milestones for assessing the success of the R61 phase, and discuss how completion of these R61 milestones will facilitate the completion of the stated goals for the R33 phase. The milestones should be specific, scientifically rigorous, and not simply a restatement of the Specific Aims. They should address critical points of the proposed program and describe research outcomes by providing quantifiable measures for success within the R61 and R33 phases of the award. Examples of milestones might include the identification of a best-in-class strategy, demonstration of targeted dosing frequency in vivo, confirmation of efficacy in animal disease models, or demonstration of feasibility to manufacture targeted formulation.

In a clearly labeled section, indicate the sequence, timeline, and location of milestones to illustrate the project schedule and the relationships between individual tasks in the project and the timeline for each task. Descriptions of the milestones must include GO/NO-GO statements to support critical parameters of the milestone that will determine whether the research should move forward or cease due to product development failures. Milestones may be indicated in the chart. Applicants may choose to use a Gantt chart or equivalent for this purpose.

Translational Partner (required): In a separate section, describe the role of the translational partner as a collaborator, including the activities and processes that would not otherwise be available to the program. Reference, but do not repeat, information submitted in the Facilities section. Describe the role of any contract research organization (CRO) serving as the industry partner in terms of scientific input, contribution and involvement in strategic planning and development process that supports their participation and fulfils a critical role in the development team. Applications derived solely from industry need to describe the advantages that sole industry sponsorship brings to the application. If an academic collaborator is proposed in an application from an industry source, describe how the academic collaborator(s) is(are) integrated into the proposed research. If the industrial /pharmaceutical company is proposing a virtual effort (making a subaward for all or part of the research), describe the oversight for the subcontracted elements of the plan.

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. 

Other Plan(s):

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.

All instructions in the SF424 (R&R) 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.

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

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

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 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 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.

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

Foreign Institutions

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

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

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

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

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

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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

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.

For this particular announcement, note the following: 

The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.  Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases. 

Overall Impact

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

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:

If successful, to what extent will the outcome from the project represent an advance in the field of prophylactic or therapeutic HIV vaccine development or the delivery of bNAb or bNAb derivatives, and will the proposed research help establish next-generation products in the pipeline?  

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 are translational partner(s) and their participation well integrated with the development of the proposed product(s)? If academic investigators are included in an application led by industry, are they well integrated into the proposed research? 

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 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 extent does the application adequately identify physical, chemical, and biological features of the proposed vaccine and/or bNAb products and are those features achievable? How well does the overall development strategy adequately address the required duration of immune response, achievement of effective bNAb concentrations, and prevention of drug resistance? Do the proposed collaborations provide a feasible approach to address the goals and objectives of the NOFO?

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

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.

Transition Milestones

Are the proposed timelines for both the R61 and R33 phases of the project and the transition milestones well-defined with specific, scientifically rigorous, feasible, and measurable benchmarks, such that if achieved, they would demonstrate the project will have high likelihood of achieving the R33 research goals with the study developed in the R61 phase? Are the proposed GO/NO-GO decision criteria appropriate for the overall advancement of the vaccine candidate, technology, or strategy?

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

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.

Applications from Foreign Organizations

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

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) (i.e., 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 policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications 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.

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 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.

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.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this 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: 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

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 Research Terms and Conditions
• 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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.

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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), 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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

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]

Angela Malaspina, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-6130
Email:  [email protected] 

Brigitte Sanders, DVM, Ph.D. 
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3209
Email: [email protected] 

Stephen Smiley, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3071
Email: [email protected] 

Barry Margulies, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-552-1324
Email: [email protected] 

Mark Hodor
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240 669-5712 
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 45 CFR Part 75 and 2 CFR Part 200.