Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Mental Health (NIMH)
Funding Opportunity Title	Targeting Persistent HIV Reservoirs (TaPHIR) (R21/R33)
Activity Code	R21/R33 Phased Innovation Award
Announcement Type	New
Related Notices	November 20, 2014 - This PAR has been reissued as PAR-15-041. January 15, 2014 - See Notice NOT-AI-14-023. Notice of Change of Program Priorities to be Supported. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-12-109
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856;93.242
FOA Purpose	The purpose of this FOA is to stimulate the development of innovative tools and strategies for curing HIV infection. HIV establishes latent infection in long-lived cells that form a reservoir of virus that persists in infected individuals even after years of treatment with highly active antiretroviral therapy (HAART). Curing HIV infection requires innovative strategies to identify and eliminate these reservoir cells. The task is especially difficult given the lack of HIV protein expression during latency and the low frequency of latently infected cells during treatment. Novel approaches are therefore sought to efficiently monitor and specifically target reservoirs of latently infected cells to facilitate the testing of strategies to cure HIV infection in vivo.

Posted Date	February 17, 2012
Open Date (Earliest Submission Date)	February 25, 2012
Letter of Intent Due Date	March 25, 2012; March 25, 2013; and March 25, 2014
Application Due Date(s)	April 25, 2012; April 25, 2013, and April 25, 2014, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable.
Scientific Merit Review	July, 2012; July, 2013; and July, 2014
Advisory Council Review	October, 2012; October, 2013; and October, 2014
Earliest Start Date(s)	December, 2012; December, 2013; and December, 2014
Expiration Date	April 26, 2014
Due Dates for E.O. 12372	Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

Research Objectives

Background

The development of highly active antiretroviral therapy (HAART) has resulted in long-term suppression of HIV replication in infected individuals to levels below the limit of detection using standard diagnostic assays. However, it has become clear that these regimens alone are insufficient to cure HIV positive individuals of their infection. Even in individuals whose levels of virus remain optimally suppressed for several years, HIV is able to recover to high levels once HAART is stopped. Identifying a strategy to cure HIV infection or effect a functional cure (in which viral levels are suppressed to very low levels in the absence of continuous therapy) is one of the highest priorities of the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH).

One particularly long-lived reservoir of virus resides in resting CD4+ memory T cells. HIV provirus has been shown to persist for years in these cells in a latent state until the cells become activated and once again begin releasing replication-competent virus. Ridding the body of latently infected cells is thus a critical hurdle in the effort to cure HIV infection. Innovative approaches to specifically target and eradicate these persistent reservoirs are needed in order to translate our understanding of HIV persistence and latency from basic research into viable eradication strategies that can be tested in vivo.

Purpose of this FOA

This FOA provides set-aside funding for high-risk, technology-driven research to address the following three critical gaps in efforts to develop and test viable strategies for eradicating HIV from the individual:

1) Development of methods for isolating, quantifying, and characterizing rare reservoir cells

In HIV-positive individuals on HAART, only about one in a million resting CD4+ T cells contain latent proviruses capable of producing replication-competent virus. Isolating, quantifying and characterizing these cells are labor-intensive and expensive. New, sensitive high-throughput single-cell analysis methods are needed to alleviate these rate-limiting steps and to facilitate in vivo proof-of-concept studies. Assays that specifically identify cells containing replication-competent virus are of greatest need.

2) Identification of markers of latency or specific re-activators of HIV gene expression that would permit targeting of reservoir cells

Since latently infected cells do not express detectable levels of HIV proteins, it is difficult to distinguish them from uninfected cells. Identification of specific markers associated with latency in primary cells to enable these cells to be depleted or selectively targeted with therapeutics is an area of particular interest for this FOA. An alternative approach is to specifically reactivate HIV gene expression, thus allowing targeting and elimination of the cells via recognition of HIV proteins. However, in employing this approach, care must be taken not to affect normal cellular processes in bystander cells which could lead to toxicity.

3) Testing of strategies to eliminate or inactivate reservoir cells

Previous studies using the so-called shock and kill approach have depended on the ability of the virus itself or the host immune response to kill infected cells following reactivation. Yet evidence suggests that these processes alone may not be sufficient. Innovative strategies to directly target reservoir cells with lethal agents or to facilitate recognition by the immune system are therefore needed. Alternatively, permanent inactivation of integrated provirus so that infectious virus can no longer be released is another potential strategy. For such approaches, efficient and selective in vivo delivery of therapeutics to the reservoir cells will be critical.

Phase Innovation Awards

This funding opportunity will utilize the R21/R33 phased innovation award mechanism. Applications for R21 support alone will not be accepted under this FOA and will not be reviewed. Although preliminary data are not required, it is recommended that applications include preliminary data if available, supporting the proposed concept. Applications should propose milestone-driven exploratory/feasibility studies for the initial 2-year R21 phase and describe how the concept will be further developed in proof-of-concept studies during the R33 phase. Clearly defined, quantifiable milestones should be listed in the application, along with a timeline or Gantt chart to delineate the projects and milestones that make up the R21 and R33 phases.

Proof-of-concept studies for the R33 phase may include, for example:

• validation experiments with larger numbers of samples,
• a transition from in vitro models to ex vivo studies using clinical samples,
• expansion of samples to include tissue samples,
• in vivo testing of approaches in humanized mice or small pilot studies in non-human primates.

Prior to the end of the second year, awardees will submit the R33 transition package, which includes the R21 progress report, which describes progress towards the initial milestones, and a clear description of how research during the R33 phase will be impacted by attainment of the R21 milestones. .. These materials will be reviewed by NIAID Program staff and NIMH Program staff (if appropriate) and then, if selected, will be transitioned to an R33 award without the need to submit a new grant application. R33 funding decisions will be based on the original R21/R33 peer review recommendations, successful completion of milestones, program priorities, and availability of funds.

Research Objectives and Scope

The goal of this FOA is to develop innovative tools and methods to facilitate the testing of viable HIV eradication strategies in vivo. Applications should outline novel approaches for monitoring or specifically targeting reservoir cells harboring integrated HIV provirus in the context of optimized HAART.

Specifically, applicants should address one or more of the following five research objectives:

• Develop innovative methods to image, isolate, quantify, and characterize individual HIV-infected reservoir cells. Assays that specifically identify cells capable of producing infectious virus are of particular interest.
• Identify means for specifically re-activating HIV gene expression in latently infected cells in vivo without affecting uninfected bystander cells. Approaches should offer significant improvement in specificity or potency over previously described activators, such as protein kinase C (PKC) activators and Histone deacetylase (HDAC) inhibitors. Agents that mimic the function of the HIV Tat protein are of particular interest.
• Identify unique biomarkers or signatures associated with latently HIV-infected primary cells in vivo. Such markers should enable targeting of latently infected cells without the need to reactivate HIV gene expression. Proof-of-concept studies on the effect(s) of depleting specific cell subsets identified as harboring a significant proportion of the latently-infected reservoir in vivo also are of high interest.
• Design approaches to specifically and efficiently target and eliminate latently HIV-infected cells in vivo. Elimination could be achieved via direct killing (e.g., using a therapeutic), by targeted removal or depletion, or by indirectly facilitating or directing a specific immune response (e.g. tagging cells for clearance by the immune system). Therapeutic HIV vaccines should not be proposed under this FOA.
• Design specific and efficient approaches to inactivate integrated HIV provirus in latently infected reservoir cells in vivo. The inactivation strategy should be permanent or should at least provide significant benefit over daily HAART (e.g. requiring no more than weekly self-administration or monthly clinical intervention).

In all cases, studies should be focused only on reservoirs that have been demonstrated to persist in the context of optimally suppressive HAART. Studies that plan to utilize a non-human primate model for in vivo proof-of-concept should substitute SIV or SHIV viruses in place of HIV where applicable. While studies involving transformed cell line models for latency may be permissible for some initial studies (e.g. high-throughput screening or assay validation), it is imperative that subsequent studies be performed using primary cells. Latently infected reservoir cells from HIV-positive individuals on optimized HAART should be used for validation studies whenever possible. Applications for developing new assays must clearly outline improvements over existing methods in terms of throughput, sample size, sensitivity, precision, accuracy, turnaround time, and cost. Studies involving a targeted therapeutic strategy must address how the approach would be efficiently delivered to reservoir cells in vivo or ex vivo without causing off-target effects and without being cleared by the immune system. Applications should also address how durable viral suppression would be sustained without the need for frequent or impractical repeated therapeutic administration or continued daily HAART.

Letters of support should be provided for critical reagents, resources, or collaborations.

Applicants should take into consideration the extreme heterogeneity of HIV in proposing how their approach may eventually be applied in the clinical setting.

Recognizing that complete eradication of HIV from the infected individual is a complex challenge, applications will be accepted that propose innovative combinations of multiple therapeutic approaches, provided that the effectiveness of each component of such combinations can be readily discerned in vivo.

NIMH will fund applications of interest that propose assays or novel therapeutic strategies for targeting HIV-1 latency/persistence in various cell populations of the central nervous system.

Note: Applications proposing any of the following will not be considered appropriate for this FOA. . .

• Approaches that are dependent on active HIV replication or ongoing HIV gene expression;
• Studies that rely on intensification of antiretroviral therapy;
• Approaches that involve non-specific reactivation of HIV gene expression through use of, for example, cytokines, HDAC inhibitors, DNA methyltransferase inhibitors, PKC activators, unless such reactivation is combined with a specific cell killing or HIV inactivation component and/or a novel, HIV-specific reactivation strategy;
• Basic research studies of viral or cellular factors involved in latency without a clearly defined translational approach for which proof-of-concept will be determined during the term of the award;
• Development of animal models to study HIV persistence, unless coupled with the testing of a novel strategy for eradication of viral reservoirs during the term of the award;
• Concepts currently under clinical investigation, unless a component of a novel combination strategy
• Therapeutic vaccines;
• Clinical Trials.

Investigators addressing basic science questions concerning the nature of the persistent HIV reservoir and its maintenance should instead consider submitting their applications in response to PA-09-152 Basic Research on HIV Persistence (R01).

Funding Instrument	Grant
Application Types Allowed	New Resubmission The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	Support for the R21 phase cannot exceed two years and total direct costs are limited to $275,000 over the R21 two-year period, with a maximum of $200,000 in direct costs allowed in any single year. The R33 award phase is limited to $300,000 in direct costs per year and cannot exceed three years. The NIAID anticipates that a maximum of fifty percent (50%) of the funded R21 phase awards will progress to the R33 award.
Award Project Period	The total project period for an application submitted in response to this FOA cannot exceed five years. Awards will support milestone-driven exploratory/feasibility proof-of-concept studies (two-year R21 phase), with possible rapid transition to expanded development (three-year R33 phase).

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

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) 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 must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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, 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 research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD, 20892-7616
Express Mail: 20817-7616
Telephone: 301-496-8426
Email: pjackson@mail.nih.gov

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

Foreign (non-US) 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 in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (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.

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 SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21/R33 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21/R33 applications; however, they are greatly encouraged to aid the reviewer in evaluating the feasibility of the proposed concept.

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? Specifically, would successful completion of the aims contribute significantly to an effective strategy for eradicating HIV from the infected individual?

Investigator(s)

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the investigators demonstrate a clear understanding of HIV persistence and latency and the challenges faced in attempting to cure latent HIV infection?

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? Have the proposed approaches been applied previously to the problem of HIV persistence and latency as evidenced by published research?

Approach

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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the proposed milestones appropriate, quantifiable, and achievable within the allotted timeframe? Will the approach demonstrate definitive proof-of-concept for the proposed strategy or provide sufficient evidence to rule out the proposed strategy? Does the proposed strategy directly address the problem of eradicating latent HIV infection?

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? Will the investigator have access to an appropriate model of HIV latency, drugs required for effective HAART in the model system (if appropriate), and the means to evaluate the proposed strategy in the context of infectious HIV? Are adequate letters of support provided for critical reagents, resources, or collaborations?

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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.

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

Not Applicable.

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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) Genome Wide Association Studies (GWAS).

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.

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. Review assignments 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/priority score.
• Will receive a written critique.

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 appropriate National Advisory Council or Board. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD(s)/PI(s) 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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 Non-Competing Continuation Grant Progress Report (PHS 2590) 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.

Potential applicants are strongly encouraged to contact the Program Contact listed below under Agency Contacts, to discuss the focus of their proposed work scope

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Karl Salzwedel, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-5332
Email: salzwedelkd@mail.nih.gov

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-6100
Email: jjeymoha@mail.nih.gov

Peter R. Jackson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD, 20892-7616
Telephone: 301-496-8426
Email: pjackson@mail.nih.gov

Devon Bumbray-Quarles
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-6213
Email: dbumbray@mail.nih.gov

Rebecca Claycamp, CRA
National Institute of Mental Health (NIMH)
Telephone: (301) 443-2811
Email: rclaycam@mail.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 Parts 74 and 92.