Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this Funding Opportunity Announcement (FOA) is to stimulate research on innovative, high risk/high impact vaccine approaches, and on critical questions related to vaccine discovery that may provide long term safe protection from acquisition of, or ongoing infection by, HIV. Developing an effective vaccine requires a better understanding of how to optimally trigger multiple adaptive T and B cell responses, and possibly innate immunity as well, so as to prevent or limit the initial infection and/or elicit responses that contain and eliminate virus that manages to establish infection and latent reservoirs.

Projects proposed will be expected to explore and test novel hypotheses to significantly impact the design of immunogens or immunization strategies leading to an effective HIV vaccine. Advances in biomedical technologies, such as molecular and structural imaging, high-throughput deep sequencing, new ways of probing antibody and cellular gene repertoires, improved animal models, novel adjuvants and more efficient vaccine delivery systems, have generated insights into the virology and immunology of HIV. Thus, it is critically important that the vaccine discovery efforts being encouraged by this FOA continue to exploit and advance these evolving research tools. While aiming to support novel approaches that significantly impact our understanding of how to create an effective HIV vaccine, this FOA explicitly encourages applications from new investigators and investigators new to the HIV vaccine field, and seeks to promote interdisciplinary cross-collaborations among virologists, immunologists, molecular and systems biologists, microbiologists, clinical scientists and other relevant specialists.

HIV continues to be an ominously deadly virus. It is estimated that more than 36 million people have died and that 35 million are living with HIV. In principle, and if ideally implemented, existing non-vaccine interventions could possibly control or even end the HIV-AIDS pandemic, but at present these fail in approximately 75% or more of infected persons. Consequently, efforts to stem the AIDS pandemic remain enormously challenging and the effort to identify and develop a safe and effective prophylactic HIV vaccine continues to be a major priority of NIAID.

Results from HIV/AIDS vaccine research to date have been equivocal, and reflect not knowing how best to confront the immense biological variability of the virus (principally in its envelope gene) and uncertainty about how to aptly exploit highly polymorphic yet fundamental host genetic loci (e.g., Ig, MHC, TCR, and other loci) that ultimately underlie immune response capacity upon vaccination. So far, only limited immunogenicity and breadth have been achieved with multiple vaccine candidates tested in Phase I and Phase II clinical trials, and only modest success was seen in the RV-144 efficacy trial (the vaccine regimen had modest efficacy of 31%). Vaccine regimens tested so far have not reliably induced sufficiently broad and potent neutralizing antibodies, though many such antibodies have now been engineered and indeed are potent enough to provide significant protection when administered passively in nonhuman primate (NHP) models. Human trials with passively administered antibody vaccines have begun. These antibodies reveal epitope targets for a potentially effective vaccine-induced antibody response. Investigators have also demonstrated in animal models that protection can be achieved without inducing antibodies. For example, vaccines based on Cytomegalovirus (CMV) vectors have been shown to protect animals from establishment of infection in about 50% of animals tested. These and other T cell vaccines are under intensive preclinical investigations to more precisely determine immunological mechanisms or correlates of protection and whether protection rates can be improved.

With the apparently more pronounced polymorphisms of key immune response loci carried in most NHP species vs. those in humans (some have yet to be fully annotated at gene sequence and expression levels in NHPs), and the highly practical importance of NHP models in assessing the mechanisms of vaccine efficacy, further studies on these loci are needed to better understand the predictive significance of these animal models in developing correlates of vaccine efficacy. For example, with improved genomic and phenomic technologies, carefully designed NHP studies are poised to show how vaccines can best induce functionally well-defined antigen-specific T and B cell responses, for example in promoting localized mucosal and/or lymphoid tissue B cell neutralizing antibody responses with appropriate somatic hypermutation and class switch recombination.

New discoveries in HIV pathogenesis and virus adaptation in the host continue to provide useful information for guiding development of effective strategies to prevent initial acquisition of infection, curb the spread of virus from initial entry to distant sites, or to eliminate infected host cells. Such hypothesis-generating leads invigorate the field and stimulate novel vaccine design and testing. There is a continuing substantial need to probe fundamental aspects of HIV immunity, both at the mucosal portal-of-entry and in critical tissue compartments (e.g., local and systemic lymph nodes) to gain insights for the future development of vaccines. Many gaps exist in our understanding of the basic biological mechanisms for inducing broad mucosal and systemic immunity, priming, protection, and tolerance. This lack of information hampers the design of effective vaccines that provide adequate protection. The types of early immune responses that will be effective remain unclear. For instance, it is still unknown and debated whether local IgA induction can result in protection. Functional genomics studies with licensed vaccines have suggested some leads to designing effective vaccination strategies by modulating dendritic cells with appropriate Toll-Like or other Pattern Recognition Receptors. While other similar leads are being explored, the HIV vaccine field must improve its fundamental understanding of viral immunity and expedite discovery of ways to achieve robust adaptive and innate immunity to prevent either initial virus acquisition or the establishment of chronic and or latent HIV infection.

Several key features of this FOA are designed to emphasize to applicants and reviewers that applications should be very different from conventional investigator-initiated R01 applications.

Given the high-innovation and high-risk research targeted by this Innovation for HIV Vaccine Discovery (IHVD) program, applicants are required to identify within the application Go/No-Go decision criteria to be achieved for the Year 2 progress report in order to enable advancement to years 3-4 funding. The Go/No-Go decision criteria will be referenced in the Notice of Award. Achievement of the stated goals ( Go decision criteria) will enable a total of 4 years of support, while failure to achieve the stated goals ( No-Go decision criteria) will result in negotiation of a reduced budget for year 3 and award close out. Applications that do not include Go/No-Go decision criteria will be considered incomplete and will not be reviewed.

The following list is not intended to emphasize or limit applications to any specific areas of research, but only to serve as a set of examples of high risk, high impact and novel research projects. Animal model evaluation of a proposed hypothesis, for example assessing vaccine immunogenicity or efficacy using simian-tropic HIV, SIV or pathogenic SHIV challenge, is strongly encouraged. Research projects and studies may include, but are not limited to, the following topics listed below:

• novel approaches to elicit durably protective cellular and/or humoral (e.g., broadly neutralizing antibody) responses against simian-tropic HIV and/or SIV or SHIV.
• novel approaches to direct protective adaptive and/or innate immune responses to relevant mucosal or systemic sites.
• development of new animal models, vectors, assays, adjuvant and/or vaccine formulations and delivery modalities, but only if specifically linked to a novel vaccine intervention strategy for prevention of simian-tropic HIV/SIV/SHIV acquisition or clearance of virus-infected cells.
• studies of novel antigen processing, presentation or priming mechanisms that generate broadly reactive or non-canonical T cells.
• exploring the feasibility/utility of novel vaccine delivery platforms to potentially better focus and improve immune responses, including but not limited to micro-needles, nanoparticles or other synthetic vectors delivered with molecular adjuvants or targeting molecules.
• use of clinical specimens to answer key questions about systemic and/or mucosal immune responses to HIV infection and vaccination in humans that could lead to vaccine improvements.
• evaluating the selective modulation of protective innate/anti-viral factors in HIV-1 vaccine strategies.
• the potential of host or non-host (e.g., allogeneic) proteins to act as immunogens alone or together with HIV/SIV/SHIV immunogens.
• previously unexplored HIV-/SIV-/SHIV- encoded targets as immunogens.
• vaccine induced/imprinted innate immune responses that can be recalled in response to subsequent vaccination or infection.
• functional genomics approaches to dissect effective adaptive and/or innate mucosal/systemic immune responses to vaccines and host responses after viral challenge.
• exploring the mechanisms by which the host microbiome impacts vaccine responses.

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

• clinical trials (however, clinical research is permitted).
• use of an oral antiretroviral therapeutic agent as part of a vaccination strategy.
• incorporation of a behavioral research component within a vaccination strategy.
• vaccines targeted to individuals with established HIV infection, e.g., for reduction of viral load; as therapeutic vaccines.
• incremental improvements of approaches already under development such as combination strategies incorporating multiple candidate vaccines or vaccines with microbicides or ART agents.
• research concepts currently being conducted in the applicant s laboratory that are supported by NIH or other funding entities.
• purely descriptive basic research or structural studies not addressing a clear hypothesis for prevention of HIV infection through vaccination approaches.
• product development.
• iterative studies that propose the next step(s) in the development of a vaccination approach currently under development or in clinical studies.
• studies that are not linked to a novel intervention strategy for prevention of acquisition of simian-tropic HIV, SIV or SHIV infection, including: development of new animal models, assay development and validation, and vector development.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

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

Other

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

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

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Vasundhara Varthakavi, D.V.M., Ph.D.
Telephone: 240-669-5020
Fax: 240-627-3153
Email: varthakaviv@niaid.nih.gov

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 FOA.

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.

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, with the following additional instructions:

Research Strategy: Present a brief overview of the scientific problem being addressed and the magnitude of the project's potential impact on HIV vaccinology. Applicants should offer a potential prophylactic vaccine solution for preventing virus acquisition or clearing virus infection, explicitly describe the novelty of the underlying hypothesis and proposed methodology in relation to the scientific problem being addressed, and highlight why the hypothesis or proposed solution to the problem is considered unconventional, unique or exceptionally novel while still being biologically plausible with a strong rationale. Applicants should clearly state how their proposed new idea/approach can be stringently tested (for example, in a well-justified vaccine animal challenge model or using a unique research cohort), provide a clear rationale for the choice of methods for the proposed work, state how their proposed new idea/approach might be implemented, indicate how the hypothesis or proposed solution to the problem challenges standard paradigms (e.g., how it differs from current or previously failed approaches), and how it will contribute, inform, or provide more than incremental knowledge to the field regardless of the outcome of the proposed work. The potential for gain in fundamental knowledge should also be described. Applicants should also describe the likelihood of obtaining a significant outcome, for example, by briefly describing past achievements that best illustrate exceptional innovativeness, ability to make paradigm-shifting discoveries or solve very difficult problems, and the impact of past discoveries or solutions.

The Research Strategy must contain a section with clearly identified Go/No-Go decision criteria for year 2 of the application. Applicants are required to identify Go/No-Go decision criteria in the application to be achieved for the Year 2 progress report and for funding in years 3 and 4. Applicants should specifically address the rationale and justification for the proposed Go/No-Go decision criteria. The Go/No-Go section may be placed at the end of the Research Strategy section, and applicants should consider the use of timelines to support the choice and timing of the Go/No-Go decision.

The Go/No-Go criteria chosen by the applicant must identify critical parameters that are essential for the success of the proposed research in subsequent years. The Go/No-Go criteria should be robust and specific to the proposed research and represent quantifiable outcomes. Note: A restatement of an application's specific aim(s) is not considered adequate for Go/No-Go criteria.

Selected examples of possible Go/No-Go criteria are:

• The formulated vaccine(s) or test immunogen(s) will demonstrate (fill-in the blank) expression and stability characteristics (e.g., in vitro and/or in vivo).
• The formulated vaccine(s) or test immunogen(s) will demonstrate (fill-in the blank) specific immunogenicity outcomes (e.g., specified breadth and potency) in (fill-in the blank) in vitro assay system(s) or in an animal model(s).
• The formulated vaccine(s) will induce a specified pre-defined threshold (fill-in the blank) of protection from a live virus challenge in a suitable animal model.
• The technology proposed will measure (fill-in the blank) under the following conditions (fill-in the blank) with (fill-in the blank) precision.

In these examples, "fill-in the blank" denotes applicant-chosen specific criteria that are essential for the success of the proposed research in subsequent years.

If applicable, applicants must indicate how the proposed research, both as to goals/objectives and approaches, differs from currently funded research in the applicant’s lab (or applicants if multi-PD/PI).

Applicants should describe any potential cross-disciplinary collaboration(s) for the proposed research. A goal of this FOA is to promote the inclusion of new investigators within multidisciplinary teams, and/or established investigators working in fields not traditionally directed toward HIV.

This FOA does not require the inclusion of preliminary data. However, applicants are encouraged to include relevant information or data that support the development of a sound rationale/hypothesis, and to provide evidence of success in overcoming scientific hurdles and making discoveries appropriate to their career stage. That is, the proposed research may require reliance upon relational and/or inferential data to establish the potential for research impact/success rather than substantial experimental data directly supporting application objectives. In lieu of investigator-generated data, it is suggested that appropriate justification for the proposed work be provided through literature citations or data from other sources, when available.

While the evaluation of immunogenicity and efficacy of vaccine approaches in animal models for a proposed hypothesis is strongly encouraged (e.g., that use simian-tropic HIV, SIV or SHIV to challenge vaccinated animals), the applicant should provide sufficient justification of the use of nonhuman primates, humanized mice, or any other animal species.

Timeline: Applicants are strongly urged to provide a detailed but brief project performance timeline in a section entitled Timeline under the heading Approach. The timeline section should indicate points on the timeline when essential aspects of the project are likely to be completed (e.g., protocol optimization, reagent generation, critical experimentation, etc.). In addition, applicants should discuss alternate plans and timelines for conducting the study in the face of adverse outcomes or problems.

Letters of Support: Collaborations are strongly encouraged, and the investigator should include letters of collaboration and agreements addressing the proposed research. Cross-disciplinary collaborations are encouraged as well.

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

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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.

Because of the complexity in the research areas being solicited, potential applicants are strongly encouraged to communicate with the Scientific/Research Contact, to discuss the responsiveness of their proposed work. NIAID staff will not evaluate the technical and scientific merit of the proposed application; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This IHVD initiative is designed to support research projects proposing innovative, high risk, high impact research to identify novel HIV vaccine concepts and targets. Preliminary data are not required. Each project is expected to develop innovative methods, to employ standard methods in innovative ways, or to test exceptionally innovative ideas. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding, or capability.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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 children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Given the critical nature of the Go/No-Go decision criterion for continuation of funding past year 2 of the award, is the proposed Go/No-Go decision criterion well-defined with a quantifiable and measurable outcome appropriate for assessing the success of the first 2 years of the application? Is the Go/No-Go decision criterion sufficiently described to enable a clear decision about its attainment? Given the potential benefits and innovation of the proposed research, is the applicant provided Go/No-Go decision criterion commensurate with the overall projects proposed advancement of the candidate, target, technology or strategy?

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.

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

As applicable for the 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.

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

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

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

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

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Jon Warren, Ph.D.
National Institute of Allergy and infectious Diseases (NIAID)
Telephone: 240-627-3032
Email: JWarren@niaid.nih.gov

Vasundhara Varthakavi, D.V.M., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5020
Email: varthakaviv@niaid.nih.gov

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@niaid.nih.gov

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.