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

This Funding Opportunity Announcement (FOA) solicits applications from institutions/organizations to participate in a multi-disciplinary cooperative research program focused on the application of novel science and technologies to transplantation immunology in three areas: 1) microbiota, 2) intravital imaging, and 3) targeted therapeutic delivery. Research in these areas has provided exciting insights into understanding and treatment of diseases such as autoimmunity, cancer, and obesity, but the application of these advances to transplantation has been limited. This FOA will help to bridge that gap by taking advantage of approaches and technologies from other fields and facilitating their application to transplant immunology research. The purpose of this FOA is to stimulate and support research in these three high-priority areas that will enhance the fundamental understanding of alloimmune responses, lead to novel approaches to prevent rejection and prolong graft survival, and ultimately result in better outcomes for transplant recipients.

Organ transplantation is the preferred treatment for end-stage organ failure when other interventions have failed. Basic, preclinical, and clinical research have provided a wealth of knowledge about the immune response in transplantation, and revealed new therapeutic opportunities. This research has contributed to significant improvements in average one-year graft survival rates, exceeding 97% for kidney recipients. Nevertheless, organ transplantation does not restore normal life expectancy, and the ten-year survival rate for kidney recipients from deceased donors is only 50%. Immune-mediated rejection remains the primary cause of both short- and long-term graft failure. In addition, long-term dependency on immunosuppressive medications is associated with undesirable side effects that contribute to transplant-associated mortality and morbidity.

Our understanding of the immune system has been enhanced by recent advances that enable more sensitive and precise imaging, while innovations in drug delivery have the potential to improve the safety and efficacy of therapeutics for multiple conditions. In addition, a growing body of research suggests that the microbiota has numerous bidirectional interactions with the host, influencing immune responses, resistance to infection, inflammation and metabolism, and is important in our understanding of the immune response, especially in the context of inflammation and infection. Despite these exciting new findings, the impact on transplantation has been modest.

Microbiota and Transplantation

The microbiota is the collective term for the complex population of bacteria, viruses, fungi, and parasites that inhabit the body surfaces exposed to the external world, including skin, airways, genito-urinary and gastro-intestinal tracts, and naso-oropharyngeal cavities. The microbiota plays an important role in host metabolism, preventing colonization by pathogenic microbes, shaping local and distal immune responses and possibly determining susceptibility to diseases. While most studies to date are focused on the bacterial population of the intestine, the microbiota of other organs plays an important role in the overall wellness of the host.

Little is known about the role of microbiota in alloimmune responses. Preliminary investigations have identified a correlation between specific changes in the gut or the graft microbiota with various transplant outcomes. Data from bone marrow transplantation studies suggest that alterations in the intestinal microbiota exacerbate inflammation associated with graft-versus-host disease (GVHD). Studies of intestinal transplants undergoing acute rejection uncovered alterations in the microbiota in the intestinal lumen. Similarly, changes in the lung microbiota of lung transplant recipients were associated with an elevated risk of bronchiolitis obliterans syndrome (BOS). However, it is not known whether the alteration in the microbiota observed in these studies was due to the immune response to the graft or to therapeutic modalities, and whether it was a marker of rejection rather than its cause. Antibiotic treatment in transplant recipients, peri-operatively and during their lifetime, may result in alterations of microbiota that affect the immune response of the host, further confounding interpretation of the influence of the microbiota on transplantation outcomes. These and similar studies reveal a complex interplay between the donor and/or recipient microbiota and local and systemic alloimmune responses and are important areas of investigation.

Intravital Imaging in Transplantation

In recent years, a variety of imaging technologies have been used to visualize living cells and tissue in real-time, and to measure physiological or pathological changes in tissues of living organisms. Intravital imaging has been used to visualize and track immune cells in situ, allowing researchers to interrogate the location, function, and interactions of specific cells. Other applications of this technology have been used to track the dynamics of viral or bacterial infection in vivo, study tumor cells or cell therapies, or detect and visualize disease progression.

Although various intravital imaging technologies have been tested in preclinical or clinical settings to visualize and evaluate the fate or function of allografts, their application to transplantation immunology has not been fully explored. Application of novel imaging technologies will allow researchers to study the immune response to the allograft in real time, visualize the trafficking and fate of cellular therapies, and enable the assessment of in situ graft responses to targeted immunomodulatory agents. Advances in this area may also support the development of diagnostic and prognostic tools to monitor graft rejection or survival that could be used in humans without surgical intervention.

Targeted Therapeutic Delivery in Transplantation

Successful organ transplantation is made possible by pharmacologic immunosuppression. At the same time, long-term immunosuppressive therapy can result in renal damage, cardiovascular morbidity, and other undesirable outcomes. Non-specific immunosuppression results in increased susceptibility to infections and malignancies. Current approaches to drug delivery can result in unpredictable (toxic or sub-therapeutic) drug concentrations in the blood. Imperfect adherence to daily or more frequent dosing contributes to poor outcomes.

Targeted delivery of drugs or other therapeutics to the organ, tissue, or cell where it is required may address some of these problems. Researchers have reported exciting applications of this technology in oncology, using liposomal encapsulation, antibody-drug conjugates, and other strategies. Similarly, liposomal techniques to preferentially target infected tissues have shown promise in the treatment of infectious diseases such as tuberculosis. Despite the progress made in other fields, transplantation has not benefited significantly from these advances.

Ideally, targeted therapeutic or drug delivery in transplantation would allow treatments to directly target key sites of immune interaction to prevent rejection or promote tolerance, while avoiding global immune suppression and its associated undesirable effects. Targeted delivery strategies often increase the drug half-life and/or bioavailability, permitting lower dosages without loss of efficacy, and provide controlled and sustained payload release, increasing drug safety. These advantages would address significant challenges in the clinical treatment of transplant recipients.

This FOA will support a multi-disciplinary cooperative group to stimulate the application of emerging technologies and science in three priority areas to transplantation research: 1) microbiota, 2) intravital imaging, and 3) targeted therapeutic delivery. This research will promote a more precise understanding of factors contributing to allograft rejection or tolerance, the response to therapeutics, and the development of more specific, targeted treatments. This cooperative group will stimulate research in transplantation immunology by fostering interdisciplinary collaborations, promoting the exchange of ideas and findings, building on developments in other fields, and facilitating the exchange of reagents and techniques.

Proposed studies may include one or more of the three priority areas. All studies must be in the context of solid organ, vascular composite tissue allograft, or pancreatic islet cell transplantation. Studies may use animal models or human specimens relevant to transplantation. This initiative will not support clinical trials. Nonhuman primate (NHP) studies are permitted, if appropriately justified and within the stated budgetary restrictions.

Microbiota and Transplantation

An objective of this FOA is to better understand the interaction between the microbiota and transplantation outcomes. Examples of research studies in this area include, but are not limited to:

• Molecular pathways by which microbial signals can influence alloimmunity;
• Identification of microbial targets for modulation of alloimmune responses;
• Microbiota associated markers of transplant outcome;
• Impact of donor/recipient microbiota on the allograft;
• Impact of microbiota perturbations before and after transplantation on alloimmune or immunoregulatory responses;
• Impact of antibiotic and immunosuppressive treatments on microbiota and transplantation outcome.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Clinical trials or clinical studies involving more than minimal risks, e.g. biopsies;
• Hematopoietic stem cell or bone marrow transplantation unless in the context of organ or islet transplantation;
• Microbial factors or microbiota studies not in the context of organ or islet transplantation;
• Fecal transplantation, unless to study the impact of microbiota alteration on organ or islet transplant outcome;
• Surveys of microbial diversity associated with disease states or phenotypes that do not specifically address immunologic pathways and mechanisms relevant to organ or islet transplantation.

Intravital Imaging in Transplantation

In order to accelerate the application of intravital imaging technologies to transplantation, research studies in this area may include, but are not limited to:

• Single or multimodal molecular imaging probes and techniques to track leukocyte trafficking and infiltration into the graft;
• Monitoring rejection and/or cellular, molecular, structural or functional changes in the graft by in vivo, real-time molecular imaging;
• In situ graft responses to therapeutic agents or cells (e.g., Treg therapy) by molecular imaging;
• Evaluation of novel imaging probes and techniques for monitoring the graft in vivo;
• Validation of graft assessment by molecular imaging techniques versus biopsies, biomarkers, or other techniques.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Clinical trials or clinical studies involving more than minimal risk, e.g. biopsies, and including clinical in vivo molecular imaging.
• Hematopoietic stem cell or bone marrow transplantation unless in the context of organ or islet transplantation;

Targeted Therapeutic Delivery in Transplantation

To advance the development of targeted therapeutic delivery in transplantation, research studies in this area include, but are not limited to:

• Targeted delivery of small molecules or biopharmaceuticals, such as immunosuppressive drugs, monoclonal antibodies, nucleic acids, or peptides using nanoparticles, drug/carrier conjugates, encapsulation, or other techniques;
• Induction of donor-specific tolerance via nanocarriers to induce tolerogenic antigen presentation.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Clinical trials or clinical studies involving more than minimal risk, e.g. biopsies;
• Hematopoietic stem cell or bone marrow transplantation unless in the context of organ or islet transplantation;
• Techniques that broadly target entire cell populations (e.g., B cells), although specific targeting of defined subsets is permitted;
• Monoclonal antibodies, unless as a component of another delivery methodology (e.g., antibody-drug conjugates);
• Pancreatic islet encapsulation.

Applicants are strongly encouraged to contact the Scientific Research Contacts well in advance of the application submission deadline to discuss the proposed research program.

Steering Committee

Program Directors/Principal Investigators (PD/PIs) from awards funded under this program will form a Steering Committee after award. The Steering Committee will serve as the main governing body for the cooperative group. Among other responsibilities, it will identify scientific opportunities, emerging needs and impediments, ensure the timely release of data through publications and/or public databases, and develop guidelines for the publication of collaborative research project results.

See Section VIII. Other Information for award authorities and regulations.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not 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 obtain 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:

Thomas Conway, Ph.D.
Telephone: 240-669-5075
Email: [email protected]

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

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

PD(s)/PI(s) must commit a minimum of 0.8 calendar months per year.

Applicants should include appropriate travel budgets to accommodate travel by the PD(s)/PI(s) to the annual Steering Committee meeting Bethesda, MD.

Support for clinical costs, research coordinators, and/or data centers is not permitted under 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, with the following additional instructions:

Research Strategy:

• Describe how the proposed research will use and apply technology and/or techniques from other fields to advance transplantation research in one or more of the following areas: 1) intravital imaging, 2) microbiota, and/or 3) targeted therapeutic delivery.
• Include a section entitled Timelines and Annual Milestones with clearly stated interim and long-term objectives and annual milestones to be achieved during the project. Identify critical decision points, and provide a detailed timeline for the completion of each goal of the proposed research project.

Protection of Human Subjects: Projects involving greater than minimal risk to human subjects (as defined at 45 CFR Part 46) are not allowed under this FOA.

Letters of Support: If the application includes samples not currently in the possession of the PD/PI, the application should include a letter of support from the person or institution controlling the samples indicating that the samples and associated clinical/phenotypic data will be made available to the applicant.

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 PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

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. 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.

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.

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? Is there a strong scientific premise for the project? 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? Does the project support the goals of this FOA in advancing transplantation research in one or more of the following areas: 1) intravital imaging, 2) microbiota, and/or 3) targeted therapeutic delivery?

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

If applicable, was documentation shown to demonstrate the availability of specimens and their associated clinical/phenotypic data?

Are the milestones and timelines reasonable and appropriate?

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?

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 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.

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.

Not Applicable

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 Data Sharing Plan (GDS).

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.

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 NIAID, 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 75 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility to:

• Determine and coordinate the scientific and administrative activities of the approved projects; set project goals and timelines; accept and implement common guidelines approved by the Steering Committee;
• Serve as a voting member on the Steering Committee (SC); participate in SC activities, and accept and implement the policies and procedures developed by majority vote of the Steering Committee;
• Work closely with NIAID staff in the scientific, technical, and administrative management of this program;
• Ensure the timely submission for publication of manuscripts (co)authored by members of the grant and supported in part or in total under this agreement and for adherence to all aspects of the consortium Publication Policy, to be determined by the Steering Committee and NIAID;
• Share reagents and resources with other investigators funded under this FOA;

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIAID Project Collaborator(s) will support the project activities through technical assistance, advice and coordination, including providing assistance with the design of the Steering Committee technical and management activities; serve as facilitator of activities, such as the selection of resources and identification of potential collaborations to further the goals of the Program. In addition, the NIAID Project Collaborator(s) will coordinate NIH staff assistance. The role of the NIAID Project Collaborator(s) will be to facilitate and not to direct the activities.
• The NIAID Project Collaborator(s) will serve as a non-voting member of the Steering Committee, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies. It is anticipated that the majority of steering committee decisions will be reached by consensus and the NIAID staff will be given the opportunity to offer input into this process, but the manner of reaching this consensus and the primary decision-making responsibility will rest with the Steering Committee, except where stated in this FOA.
• The NIAID Project Collaborator(s) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Government, via the NIAID Project Collaborator(s), will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
• Release of each annual funding increment by NIAID will be based on an NIAID review of progress towards achieving the previously agreed upon research goals, interim objectives and milestones. It is recognized that project goals may require revision and re-negotiation within the scope of the original award during the course of the project period. The NIAID reserves the right to terminate or curtail a study (or any individual award) in the event of a substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the approved project.
• NIAID staff may appoint other investigators as consultants or subject matter experts to provide additional perspective.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee will coordinate and facilitate research activities for the overall program; facilitate compliance with the data- and other resource-sharing policies; and promote optimal research flexibility, synergy, and efficiency. The Steering Committee will include one PD/PI from each awarded U01 as a voting member and the NIAID Project Collaborator(s) as non-voting members. Awardees will be expected to collaborate, share reagents, assays, animal models, human samples, and experimental results that would facilitate the research activities of other members. Subcommittees of the Steering Committee may be established as needed to make recommendations on other activities of the cooperative research group.

The Steering Committee will:

• Serve as the main governing board;
• Identify scientific opportunities, emerging needs, and impediments;
• Develop guidelines for publication of collaborative project results;
• Prepare annual reports;
• Provide guidance and recommendations to investigators regarding study implementation and conduct.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIAID staff voting, one NIAID designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Jeffrey Rice, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-627-3552
Email: [email protected]

Nasrin Nabavi, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-627-3538
Email: [email protected]

Thomas Conway, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5075
Email: [email protected]

Jenna Briggs
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5137
Email: [email protected]

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.