Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institute of Allergy and Infectious Diseases (NIAID)
93.855
This Funding Opportunity Announcement (FOA) invites applications from institutions and organizations to conduct research focused on elucidating mechanisms of Fc-dependent, antibody-mediated killing of infected or aberrant cells, or antibody-mediated therapeutic ablation of cells implicated in immune pathologies, including autoimmune and allergic diseases. Studies supported by this FOA are expected to define variables that affect efficiencies of antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cell-mediated phagocytosis (ADCP), both in vitro and in vivo. U01 awardees will be expected to attend annual Program Progress/Steering Committee meetings and present progress to fellow awardees and to NIAID program staff. The goal of the meetings is to facilitate collaborations between funded investigators and to accelerate development of mechanistic models that incorporate the collective findings of this program. Advances in our understanding of these Fc-dependent killing mechanisms will inform more efficient design and optimization of ablative antibody therapeutics and may also inform design of vaccines that preferentially elicit ADCC- or ADCP-efficient antibody responses.
This FOA uses the U01 grant mechanism, while the companion FOA, PA-19-020, uses the R21 mechanism. Short-term high risk/high reward projects with limited or no preliminary data or utilizing existing data may be most appropriate for the R21 mechanism.
January 2, 2019
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
Purpose
The purpose of this Funding Opportunity Announcement (FOA) is to support research that addresses knowledge gaps in the mechanisms of Fc-dependent, antibody-mediated killing of infected or aberrant cells, or antibody-mediated therapeutic ablation of cells implicated in immune pathologies, including autoimmune and allergic diseases. Targets of therapeutic Fc-dependent, antibody-mediated killing include: pathogen-infected cells, malignant cells, and host cells implicated in immune pathologies (e.g., autoimmune and allergic disease). Studies supported under this program will be focused on either or both of two killing mechanisms: antibody dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). There is growing recognition of ADCC and ADCP in humoral control of infection, a research area within the mission of NIAID. Progress in this area will enable more efficient design and optimization of ablative antibody therapeutics and may also inform the design of vaccines that elicit ADCC or ADCP-competent antibody responses.
Background
Therapeutic monoclonal antibodies have shown much promise for the treatment of infectious and immune-mediated diseases and cancer. Antibodies contain two general types of domains; a bivalent F(ab')2 domain that is highly variable and responsible for the ability of antibodies to recognize an extraordinarily large universe of antigens, and a constant (Fc) region associated with functional activities. The subclass or isotype of the Fc region influences functional capabilities of the antibody. Among these functions are killing of pathogens or infected host cells through complement-mediated killing or killing of cells through binding of Fc domains to Fc receptor (FcR)-bearing effector cells.
There is growing recognition of the importance of two Fc/FcR-dependent mechanisms of antibody-mediated protection in the destruction of infected host cells. These mechanisms are dependent upon recruitment of effector cells bearing FcRs that, upon interaction with the Fc domains of antibodies bound to infected cells, are activated to deploy cytotoxic programs to destroy their targets.
The first mechanism is antibody-dependent cellular cytotoxicity (ADCC). Multiple effector cell types are competent to kill target cells via ADCC, at least under in vitro assay conditions. These cell types include: NK cells, neutrophils, macrophages, monocytes and eosinophils. These FcR-bearing effectors kill their targets through release of cytotoxic molecules following engagement of their FcRs by antibodies bound to the target cell surface.
The second mechanism is antibody-dependent cell-mediated phagocytosis (ADCP). Multiple FcR-bearing effector cell types have demonstrated proficiency in ADCP, including neutrophils, macrophages, monocytes, and dendritic cells. In these cases, Fc/FcR interactions between target bound antibodies and FcR-bearing effector cells promote engulfment and destruction of target cells by effector cells.
For therapeutic applications, monoclonal antibody development is commonly focused on cytotoxic destruction of infected, malignant, or pathogenic host cells. On infected cells, the target antigen may be a pathogen-derived epitope displayed on the cell surface. For malignant cells, it may be a tumor-associated antigen. In the case of autoimmune or allergic disease, the antibody therapeutic may be used for selective ablation of cell types responsible for immune pathology.
The importance of antibody isotype and glycosylation status on ADCC and ADCP efficiencies is widely recognized, and these two parameters are active areas of research. However, it is still difficult to predict ADCC or ADCP killing efficiencies based on antibody isotype and Fc glycosylation patterns alone, making it challenging to reliably design antibodies that mediate Fc-dependent killing in vivo . For example, antibodies that recognize identical or overlapping epitopes on a target cell antigen may have dramatically different abilities to mediate ADCC or ADCP, even when they are engineered to have identical Fc regions and glycosylation patterns. In addition, the relative contribution of each killing mechanism to in vivo efficacy is difficult to evaluate and may vary even within an individual, depending on anatomical location and the microenvironment of target cells. A key microenvironmental variable is the availability and type of effector cells required for Fc/FcR-mediated killing. Preliminary evaluation of antibody therapeutics continues to rely on empirical testing of each antibody for cytotoxic activities under in vitro assay conditions. Even when ADCC-competent antibodies are identified and optimized for highly efficient in vitro killing, the results often fail to translate to in vivo efficacy.
Elevation of NK cell numbers during infection has led to speculation that they may serve as primary effector cells for ADCC. However, NK cells have additional antibody-independent roles in innate control of infection and their increased frequencies may be independent of potential roles as effector cells for ADCC-mediated killing in vivo. Importantly, closer consideration must be given to the role of other cell types present at sites of infection as potential effectors of antibody-mediated killing. For example, alveolar macrophages may play critical roles in the control of respiratory infection through ADCC, ADCP, or both killing mechanisms. In fact, cancer studies suggest that while NK cells are the most commonly used effector cells for in vitro ADCC assays, monocytes and macrophages are often identified to be the main effectors of antibody-mediated killing of cancer cells in vivo.
Research Objectives and Scope
The goal of this initiative is to expand our mechanistic understanding of two pathways of Fc-dependent, antibody-mediated killing: ADCC and ADCP. These are highly complex processes that are understudied and for which preliminary data may be severely limited.
This FOA was developed to support high priority research for mechanistic understanding of ADCC and ADCP, translation of mechanistic observations made using in vitro systems for evaluation of in vivo efficacy, and to address complications associated with interpretation of in vivo results. In June 2017, NIAID assembled a group of external scientists representing academic, biotechnology and pharmaceutical sectors to identify research gaps that should be addressed to accelerate our understanding of the mechanisms of ADCC and ADCP, both in vitro and in vivo . Consensus recommendations for addressing research gaps were incorporated into the list of high priority research areas below.
This initiative will support research that increases our fundamental understanding of ADCC and ADCP. Examples of relevant model systems for functional, mechanistic evaluation of ADCC- and/or ADCP-mediated killing include: cytotoxic killing of infected human cells ( in vitro), in vivo infection models (animal models only), and ex vivo studies using human tissues; the use of model antigens expressed on the target cell surface (which may include tumor antigens); and cytotoxic killing of cells implicated in human immune-mediated disease, (e.g., studies using experimental or licensed human monoclonal antibodies for ablation of cell types associated with autoimmune disease or allergy.)
Under this FOA, high priority research areas include, but are not limited to:
Hypothesis-driven, mechanistic studies that increase our understanding of the molecular mechanisms of cytotoxic killing by ADCC and/or ADCP. Studies must include evaluation of human monoclonal antibodies. While animal models may be used for in vivo validation, applications should include justification for the proposed animal models, with discussion of their translational relevance to our understanding of ADCC and/or ADCP in humans.
Descriptive studies to evaluate the contributions of the availability, anatomical distribution and phenotypic characteristics of appropriate effector cell types in human tissues to in vivo killing mechanisms and overall efficacy of therapeutic antibodies. It is expected that knowledge gained through these studies will improve our ability to predict Fc-dependent, cytotoxic functions of antibodies, and will inform design, development and optimization of ablative monoclonal antibody therapeutics for treatment of infectious diseases, autoimmune disease, allergy, and cancer. Results may also inform the design of therapeutic vaccines that preferentially elicit antibodies with Fc-mediated killing functions.
Research topics that fulfill program objectives include, but are not limited to:
Availability, frequencies, and phenotypes of physiologically relevant human effector cell types at tissue sites, coupled with evaluation of relevant killing mechanisms at sites chosen.
FcR expression patterns on individual human effector cell types, including:
Variations in FcR expression patterns among cells of a particular effector cell type, as a function of maturation stage, activation status, and anatomical environment.
Variations in post-translational modification of FcRs, both within categories of effector cells or among different effector cell types.
Target antigens and how the nature of epitopes bound by human antibodies affect cytotoxic killing.
Valency or density of human antibodies bound to epitopes on the target cell.
Signaling or other biochemical pathways involved in ADCC or ADCP killing.
Optimal epitope characteristics, which may include: physical distance between the targeted antibody epitope and the target cell membrane; epitope orientation; epitope accessibility, etc.
Conformational requirements/changes associated with binding of human antibodies to target cells, as required for efficient mediation of ADCC and/or ADCP cytotoxicity.
Antibody paratope (or (Fab')2, or idiotype)-associated factors: Antibodies with closely related variable regions may mediate widely variable efficiencies of ADCC or ADCP. Killing efficiencies do not necessarily correlate with affinities of antibody for target antigens, even when specific for the same epitope and bearing identically Fc domains engineered for optimized ADCC or ADCP function.
Studies to perform comparative, mechanistic evaluation of ADCC and/or ADCP using existing antibody collections obtained during design or development of therapeutic monoclonal antibodies are acceptable, with strong justification for the value of the antibody collection(s) for proposed hypothesis-driven, mechanistic research.
Applications including t he following types of studies will be considered non-responsive and will not be reviewed:
Clinical trials (the NIH definition of clinical trials is available at http://grants.nih.gov/grants/policy/hs/glossary.htm).
Studies on non-human monoclonal antibodies
Studies involving antibodies that recognize AIDS, HIV, or SIV epitopes, as studies on killing of HIV-infected cells by HIV-specific antibodies are funded through other solicited research programs.
Studies exclusively examining antibodies to tumor-associated antigens, unless studies also include other model antigen systems and/or are designed such that results will be more broadly applicable to understanding of ADCC or ADCP-mediated killing in infectious or autoimmune diseases.
Studies for which the primary objective is the design or development of therapeutic monoclonal antibodies
Studies solely focused on evaluation of antibody isotype
Studies solely focused on antibody glycosylation, as such studies on the roles of glycosylation of cytotoxic killing are already supported through active investigator-initiated grants and other solicited research programs.
Steering Committee : A Steering Committee (SC) will be formed with the PDs/PIs and NIAID Program Officer to 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 . Annual Program Progress meetings will be held to discuss the progress of individual research programs. PD(s)/PI(s) are expected to participate in Program Progress meetings by presenting the aims, status and highlights of their project, attend annual face-to-face SC meetings to be held immediately following adjournment of Program Progress meetings, and participate in SC-related activities and teleconference meetings. NIH staff may appoint other subject matter experts as non-voting members of the Steering Committee to provide additional expertise and perspective.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Need help determining whether you are doing a clinical trial?
NIAID intends to commit $2.0M in FY 2020 to fund 3-5 awards.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Governments
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:
Zhuqing "Charlie" Li, Ph.D.
Telephone: 240-669-5068
Fax: 301-480-2408
Email: liz@niaid.nih.gov
If the research histories of the PD(s)/PI(s) and collaborators do not include publications specifically focused on mechanisms of ADCC or ADCP-mediated killing, applicants should document relevant expertise for the proposed Specific Aims. Relevant experience may include (but is not limited to): experience in evaluation of aspects of antibody structure/function, antibody engineering, or in the study of effector cell types relevant to Fc-dependent, antibody-mediated killing.
All instructions in the SF424 (R&R) Application Guide must be followed.
Research Strategy:
Applicants should provide a rationale for how the proposed work will contribute to advancing our understanding of the fundamental molecular and cellular mechanisms of ADCC- and/or ADCP-based killing.
Because our understanding of ADCC and ADCP is very limited, both descriptive research and hypothesis-driven, mechanistic research are acceptable under this FOA and preliminary data that specifically address mechanisms of Fc-dependent, antibody-mediated killing are not required. However, applicants should provide strong rationale for how proposed studies will fill knowledge gaps relevant to Fc-dependent, antibody mediated killing and provide preliminary data, where possible, to demonstrate feasibility of the proposed approaches.
If included in the research strategy, applicants should provide thorough justifications for selection of in vivo animal models and ex vivo human tissues, with explanations for how results are translationally relevant to in vivo Fc-mediated killing in humans.
Applications should include Gantt charts with proposed milestones and anticipated timelines.
The following modifications also apply:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous?If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific for this FOA:
As appropriate for the specific aims of the application (mechanistic and descriptive studies):
How well will the proposed mechanistic or descriptive studies address knowledge gaps in Fc-dependent, antibody-mediated killing that will lead to a better understanding of the fundamental molecular and cellular mechanisms of ADCC- and/or ADCP-based killing?
For in vivo animal/ ex vivo human studies: How well will findings from animal models or ex vivo human tissues inform the ability to predict in vivo mechanisms of ADCC or ADCP-mediated killing?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific for this FOA:
If the PD(s)/PI(s), collaborators, and other researchers have no records of publication specifically focused on mechanisms of Fc-dependent, antibody-mediated killing, do they have demonstrated expertise in areas relevant to the proposed Specific Aims?
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 included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? If the project is in early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented appropriate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
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?
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee willevaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is goals and research justified in terms of the scientific strategy proposed?.
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
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic 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.
Information regarding the disposition of applications is available 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.
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.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
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.
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 74 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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described belo w:
Additionally, an agency program official or IC program director, which may be the same as the project scientist, will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
Areas of Joint Responsibility include:
Steering Committee: The Steering Committee of the Fc-Dependent Mechanisms of Antibody-Mediated Killing program 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 the PD/PI from each awarded U01 as a voting member and the NIH Program Officers as non-voting members.
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 NIH staff voting, one NIH 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.
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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
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Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Stacy E. Ferguson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3504
Email: fergusonst@mail.nih.gov
Zhuqing "Charlie" Li, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5068
Email: liz@niaid.nih.gov