Part 1. Overview Information

Key Dates

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to pair Bioengineers and Immunologists to leverage emerging innovative knowledge in physical and computational sciences for the design and development of an HIV-1 vaccine.

The objective of this FOA is to support small multi-disciplinary teams that include a product development translational partner. This will foster the application of novel and practical bioengineering solutions to solve challenging and persistent problems in the production of a safe and effective preventive HIV-1 vaccine. Potential research areas for the improvement of HIV-1 vaccine effectiveness may include enhancing the magnitude, quality, and durability of the immune responses.

Background

A safe and effective HIV vaccine is essential to end the HIV pandemic. Despite substantial scientific progress, the development of such a vaccine has proven elusive. Whereas traditional vaccines against viral pathogens, such as influenza or hepatitis B, elicit antibody (Ab) responses that effectively clear infections, the HIV-1 envelope has presented a wide array of challenges to successful HIV vaccine development. These challenges include wide genetic diversity in envelope proteins, variable patterns of glycosylation, and immune evasion.

Of the six HIV vaccine efficacy trials completed to date, only one, RV144, has yielded moderate success with an estimated 60% efficacy at 12 months and 31% efficacy after 42 months. RV144 activity correlates with an early but nondurable non-neutralizing antibody response against the variable V1/V2 region of the Env protein and antibody-dependent cellular cytotoxicity. Several strategies are currently being pursued to amplify the strength, breadth, and durability of the RV144 response. An alternative approach to developing an HIV vaccine is based on understanding the immune response to HIV infection and finding ways to generate and enhance that response through vaccination. Along this pathway, researchers have been able to identify and isolate broadly neutralizing antibodies (bNAbs) that have developed naturally among some HIV-infected persons. These bNAbs have been shown in the laboratory to inhibit most HIV strains from infecting human cells. However, when bNAbs have been elicited during the course of HIV infection in these individuals, their development is atypical in a number of ways. This has prompted significant efforts to design vaccines that induce these bNAbs. However, bNAbs are often difficult to induce, their production is disfavored over other types, and they need to overcome host control roadblocks. Consequently, current immunization strategies may be inadequate to successfully enhance the breadth, potency and durability of immunity against HIV-1.

A promising avenue of research to accelerate the development of a safe and efficacious HIV-1 vaccine is to integrate, adapt, and optimize various existing and emerging bioengineering approaches to provide breakthroughs in the unsolved issues of developing a preventive HIV-1 vaccine. ?Bioengineering solutions have been shown to actively modulate immune responses toward desired functions by exploiting biomaterials as carriers, scaffolds and modulatory materials, and by controlling the immune targets through imprinting specific spatial, timing, dosage, sequence and combinations, cellular and environmental contexts. In fact, harnessing the power of the immune system by engineering nucleic acids, proteins, biomaterials, cells, and tissues has shown promise in biomedical interventions of diseases and conditions such as autoimmune disorders, infectious diseases, cancer, wounds, and foreign body responses. Bringing immuno-engineering to bear on the HIV-1 pandemic may therefore significantly yield new advances toward a preventive HIV-1 vaccine.

To expand cross-disciplinary collaboration in these areas, the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Biomedical Imaging and Bioengineering (NIBIB) convened experts from these diverse fields for a workshop in September 2018 to expand and facilitate the adaptation of engineering principles and techniques to rationally design HIV-1 immunogens and immunization regimens and create enabling technologies for their practical implementation.

This FOA creates an opportunity to synergize expertise between bioengineers and HIV immunologists to help with the design, display and delivery of HIV immunogens coupled with adjuvants/immunomodulators. In addition, an opportunity to add a translational partner with product development expertise to address the considerable manufacturing challenges provides novel, unprecedented opportunities for collaboration in developing an efficacious preventive HIV-1 vaccine.

Research Objectives

This FOA will support the design, development, optimization and early manufacture of promising HIV-1 antigen-adjuvant formulations across preclinical, translational and clinical research toward the goal of a safe and effective HIV vaccine.

Due to the high-risk, high-impact nature of the research, this FOA will use milestone-driven, phased research activities with investigator-provided milestones. Support will be provided for up to three (3) years for the R61 phase, and up to two (2) years of support may follow for the R33 phase. The R61 phase will support the initial hypothesis-driven design, refinement and characterization of novel approaches/platforms. The R33 phase will support the preclinical development of promising designs/platforms optimized in the R61 phase to facilitate future translation to clinical testing. These activities might include not only the evaluation in animal models for the improvement of HIV-1 vaccine potency and durability, but also the evaluation of their developability as vaccine products.

Three (3) months prior to the end of the R61 phase, awardees will submit the R33 transition package, which will be evaluated by NIH Program staff for adequacy of completion of milestones. R33 transition decisions will be based on successful completion of negotiated milestones, as well as on Program 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. For more information, see the Phased Award SOP (https://www.niaid.nih.gov/research/phased-award-sop).

Examples of activities for R61 phase include, but are not limited to:

• Engineering and production of new delivery vehicles with novel biomaterials, liposomes, micelles, nanoparticles, dendrimers of proteins/peptides and/or nucleic acids vaccines to improve biodistribution and/or immune differentiation to bypass the limitations of natural immunity.
• Novel delivery modalities of single or multiple antigens, e.g., sequentially, controlled release with implantable pumps, use of phosphorylated proteins, microneedles.
• Stimulators/modulators for directed immune engineering, chimeras with antigens and multivalent antigen systems, synthetic adjuvants, next generation adjuvant approaches.
• Strategies to program immunity, understand heterogeneity within and between populations, and rescue impaired immunity.
• Investigating the effects of route of immunization, dose, dosage form, and dose-sparing capacity of particulate formulations, and particle distribution and kinetics of immunogen on immune responses.
• Development of image-guided approaches to visualize and characterize immunogens and immune responses at the molecular, cellular, and organ levels.

Examples of activities for R33 phase include, but are not limited to:

• Conducting pre-formulation/formulation studies on particulate antigen combinations to understand the interactions and compatibility of components (e.g., excipients, buffers, pH) and effect on antigen epitope integrity and its performance.
• Use of animal models to advance hypothesis-driven studies that are supportive of immunogen advancement, efficacy, safety.
• Developing an efficient process for early stage/pre-clinical studies and immunogen manufacture, which could be adapted to scale-up studies and lead to the production of clinical grade material in conformance with current good manufacturing practices (cGMP).
  

Translational Partner(s)

Applications submitted to the FOA must document collaboration by at least one translational partner. For the purposes of this FOA, 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.

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

• Research Focus or Research Support Unit to perform Clinical Trials of candidate HIV vaccines.
• Applications proposing only the R61 mechanism, or only the R33 mechanism.
• Applications that do not provide milestones for both the R61 and R33 phases of the award.
• Research plans that do not minimally include dual expertise in bioengineering and immunology
• Purely descriptive basic research or structural studies not addressing a clear hypothesis for prevention of HIV-1 infection through vaccination approaches.

Section II. Award Information

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)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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

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

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

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

Applicant organizations

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

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

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

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

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

3. Additional Information on Eligibility

Number of Applications

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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:

Chelsea Boyd, Ph.D.
Telephone: 301-761-6664
Email: chelsea.boyd@nih.gov

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

Specific Aims: Briefly describe in clearly demarked sections the specific aims for the R61 and R33 phases of the proposed research.

Research Strategy: 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. Discuss how linking expertise in bioengineering and immunology in the proposed approach represents an advancement beyond the vaccines currently being developed, and how the proposed development pathway helps to establish the next generation of products for possible clinical testing. If the proposed approach/rationale relies on research in fields outside the current HIV vaccinology (e.g., cancer, autoimmune disorders, diabetes, etc.), the applicant should discuss their relevance to the proposed approach and how progress in these fields enables the proposed strategy.

Milestones (required): In a clearly labeled section, applicants must include milestones for BOTH the R61 and R33 phases of the award. Milestones that are a restatement of application Specific Aims do not meet the definition of milestones used here. 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 should address critical points required for significant advancement in understanding immunity, vaccination, vaccine development, or other key processes and should provide a concrete basis for future judgment of whether advancement to the R33 phase is adequately justified. Consequently, milestones should be both realistically achievable, and significant enough to represent substantial scientific or developmental advancement if they are met. The following milestones are examples that may be included:

• If the platform or rationale comes from a non-HIV field, completion and submission of preliminary studies that support the biological rationale for the development strategy and/or scheme of the new platform and supporting HIV data.

• Demonstration of improvement of magnitude and durability of immune responses. If applicable, provide a comparison to existing immunogenicity assays discussing the advantages of the proposed approach and addressing the unmet need.

• Evaluation of the performance, immunogenicity, efficacy and toxicity of HIV vaccine candidates in animal models.

• Development of lead immunogen/adjuvant antigen formulation into an efficient, stable and reproducible process.

• Generation of a pilot lot and/or scale-up studies based on optimized conditions that can subsequently lead to the production of clinical grade material in conformance with current Good Manufacturing Practices (cGMP).
  
• Development of methods to evaluate compositional quality on critical components in selected platform, for example, but not limited to, quality, manufacturability and stability/degradation of individual components.

• Establishment of quality assurance and quality control, methodology and development protocols for generation of HIV antigen-adjuvanted formulations for codelivery.

Translational Partner: 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 contracted elements of the plan.

Timelines and/or Gantt charts (optional): In a clearly labeled section, applicants may provide descriptive timelines and/or Gantt charts for the proposed studies. If provided, applicants are encouraged to consider linking the timelines/Gantt chart elements to the proposed milestones.

External Advisory Committee (EAC): An External Advisory Committee (EAC), consisting of independent experts in the areas of research that the project addresses, will be identified soon after award. The EAC, together with the PD/PI, will be responsible for determining progress of the PD/PI and other investigators during an annual site visit and provide guidance for the future direction to the PD/PI and Program Staff. Potential members of a proposed EAC should NOT be named in the application and EAC members must not be recruited or contacted prior to review and award.

The following modifications also apply:

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

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.

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

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

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

4. Submission Dates and Times

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.

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.

7. Other Submission Requirements and Information

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 Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

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:

Significance

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

Specific to this FOA:

Does the rationale for the proposed project clearly explain how the outcome(s) will directly contribute to an effective strategy for the design and potential development of a vaccine to prevent acquisition of HIV-1 infection? Does the proposed strategy represent an advancement beyond ones currently being developed and will the proposed development help to establish the next generation of vaccines in the pipeline? Will achievement of the Specific Aims represent significant advancement in understanding immunity, vaccination, vaccine development, or key processes?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA

Does the research team collectively have adequate expertise in the fields of bioengineering and immunology as evidenced by training, experience and peer-reviewed publications? Is there evidence of strong, appropriate, multidisciplinary collaboration? Are the translational partner(s) and their participation well integrated with the development of the proposed vaccine release product? 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?

Specific to this FOA:

Does the outlined development program embody innovation by leading to, and supporting the creation of a new and innovative HIV-1 preventive vaccine? Is this new product in line with the objective of creating the next generation of vaccines?

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 FOA:

Does the proposed strategy directly address the challenges of developing an effective HIV-1 vaccine? Will the approach demonstrate definitive proof-of-concept for the proposed strategy or provide sufficient evidence to rule out the proposed strategy? If the application uses preliminary data or experimental approaches derived from an alternative research field (e.g., cancer, autoimmune disorders, diabetes, etc.) to justify development, do the information and preliminary data support its applicability to development of an HIV-1 vaccine?

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?

Study Timeline: Milestones (required), Gantt Chart (optional), and Timelines (optional)

Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame for the research elements they support? Are the Go/No-Go criteria appropriate for the described testing and integrated into the milestones? Are the milestones well-integrated into the research strategy? Is the timeline proposed to meet specific objectives for the project appropriate?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories 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 Animal 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

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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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.

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

• 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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

3. Reporting

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare 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

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

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

Clinical Research on HIV Vaccines
Patricia D'Souza, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3037
Email: pdsouza@niaid.nih.gov

Immunogen Design and Immunology
Angela Malaspina, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-6130
Email: amalaspina@niaid.nih.gov

Preclinical Testing of Vaccines
Jon Warren, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3032
Email: jwarren@niaid.nih.gov

Chelsea Boyd, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6664
Email: chelsea.boyd@nih.gov

Jenna Briggs
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5137
Email: jenna.briggs@nih.gov

Section VIII. Other Information