Part I Overview Information



Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Allergy and Infectious Disease (NIAID), (www.niaid.nih.gov)

Title: Immune Mechanisms of Virus Control (U01/U19)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-AI 08-013

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.856

Key Dates
Release Date: April 16, 2008
Letters of Intent Receipt Date: July 18, 2008
Application Receipt Date: August 18, 2008
Peer Review Date: January 2009
Council Review Date: January 2009
Earliest Anticipated Start Date: March, 2009
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/  
Expiration Date: August 19, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
         1. Principal Investigator Rights and Responsibilities
         2. NIH Responsibilities
         3. Collaborative Responsibilities
         4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

This Funding Opportunity Announcement (FOA) represents the second phase of the NIAID Immune Mechanisms of Virus Control Program (IMVC).  The first phase was awarded as exploratory R21 grants in fiscal year 2007 (RFA-AI-07-008).  All qualified investigators are invited to apply; prior funding under the first phase or through NIAID or NIH is NOT required.

This FOA will support studies on the immunological parameters of virus infection and vaccination that are important for understanding the key molecular and cellular mechanisms involved in the natural control of infection, the induction of protective immunity by vaccination, or the immune-mediated processes that cause pathology after virus infection or vaccination.

All applications must propose studies on at least one of the NIAID Category A, B, or C or other Emerging/Re-emerging viruses of concern to human health (for list see http://www3.niaid.nih.gov/research/topics/emerging/list.htm). In addition, studies on other viruses that pose serious threats to human health may be proposed. However, at least one of the specific aims in U01 grants and one of the projects proposed in U19 grants must be solely dedicated to viruses on the list of NIAID Category A, B, or C or other Emerging/Re-emerging viruses. HIV studies are excluded from this FOA.

The goal of the program is to discover and define novel basic immune mechanisms that provide a more sophisticated understanding of the immune response to virus infection, and provide potential new targets for future vaccine and therapeutic drug development. It is NOT the purpose of this program to apply currently accepted immunological concepts to the development of improved anti-virus vaccines or therapies. For example, conventional antibody measurements used to test new vaccine candidates would not be considered responsive in the absence of studies on immune mechanisms of antibody protection.

Background

The lack of effective vaccines and drug treatments for many viruses, especially those identified by the NIAID as potential weapons of bioterrorism and emerging and re-emerging infections, presents a public health concern of significant proportions. Host defenses against viruses involve both innate and adaptive immune mechanisms, but the basic processes and the interactions of these two arms of the immune response in anti-virus defense are incompletely understood, especially in humans. Immune detection of virus infection and development of immediate responses depends upon the innate immune system, comprised of cells located in all major organs and tissues of the body, which express receptors dedicated to the detection of microbial components.  Key virus-detecting receptors include the nucleic acid-recognizing Toll-like receptors (TLR) 3, 7, 8, and 9, and the cytosolic RNA receptors RIG-I and MDA-5.  Immediate responses include secretion of type 1 interferons and activation of responding cells that include dendritic cells (DC), macrophages, neutrophils, natural killer (NK) cells, NK T cells, and ?d T cells. Activation of B-1 B cells leads to the generation of natural antibodies that may have anti-virus properties. Further, presentation of virus antigens to antigen-specific T cells promotes development of adaptive immune responses to viruses, including the proliferation and maturation of cytotoxic T cells and production of virus-neutralizing antibodies.  In response, viruses have evolved multiple mechanisms to thwart host defenses.  For example, the influenza virus NS1 protein interferes with innate immunity by antagonizing interferon-mediated gene activation and human herpesviruses encode several proteins that interfere with the adaptive immune response by downregulating host major histocompatability complex (MHC) molecules on the surface of antigen presenting cells (APC). Thus, a better understanding of the underlying immune response mechanisms to virus infection could provide new approaches to generate safe and effective vaccines and therapeutics. 

Analysis of anti-virus immune mechanisms in humans presents many challenges, some of which are now being addressed through the application of new research approaches and tools.  Although in most cases only peripheral blood and small biopsy samples are available for analyses, more efficient analytical methods and availability of a growing number of specific reagents are enabling more sophisticated studies of human anti-virus responses.  Among these are analyses of T and B cell repertoires, methods such as peptide/MHC tetramer staining to track antigen-specific cells, new imaging techniques to detect immune cell interactions, and multiparameter flow cytometry to sort subsets of lymphocytes.  Genomic, proteomic, and systems biology approaches have led to the discovery of new molecules and novel functions of known proteins in the immune response. Development of better animal models, including knockout and transgenic mice, use of siRNA to abrogate specific gene products, and expression of human molecules in animals are enabling novel insights into human anti-virus immunity. This initiative encourages the use of a wide variety of state-of-the-art approaches to better define immunity to virus infection and vaccine responses.

Research Objectives and Scope

The IMVC program will support research using appropriate human and animal studies to address basic immunological questions leading to the discovery of novel immune-based mechanisms relevant to the prevention or control of human virus infection. Successful applicants will justify their choices of experimental systems and approaches in the context of their ultimate physiological relevance to human disease. Proposed research must be focused on the analysis and characterization of host immune mechanisms to address basic scientific questions on the immunology of anti-virus responses, generated either to infection or vaccination.

Immune recognition of infected cells, anti-virus defenses, and mechanisms of virus clearance in different tissues are among the major research areas in need of further study; several specific areas of interest and examples are briefly described below. These and other research areas may be addressed in response to this FOA in the context of defining new immune mechanisms relevant to viral disease in humans.

Early innate immune responses. Innate immune recognition and activation in response to virus infection are not yet well understood, but are of practical importance for several reasons: vaccines and adjuvants may be more effective if they closely mimic (or in certain cases enhance) the immune triggering of natural infections; better understanding of the anti-virus activity of antimicrobial peptides, cytokines, micro RNA molecules and cellular effector mechanisms may lead to novel antiviral therapies; and the ability to prevent or blunt the damaging effects of innate immune system activation (e.g., “cytokine storm” and other undesired inflammatory responses) may lead to better clinical outcomes.  Basic studies are needed on innate immune responses to specific viruses as well as virus evasion mechanisms. Examples of research in these areas include, but are not limited to:

Innate/adaptive interface. The generation of protective immunity appears to be an outcome of a tightly regulated, yet poorly understood, transition from innate to adaptive immunity. As the immune response to virus infection or vaccination matures with time, the innate response leads to activation of the adaptive immune system, and expansion of virus antigen-specific T and B cells. This transition to adaptive immunity is a highly dynamic and complex process.  In some cases, antibody and cytokine responses do not lead to host protection or clearance of the virus, or there may be a failure to down-regulate acute inflammatory responses and transit to an adaptive response. Important areas for further basic research include studies of mechanisms that induce or repress inflammation, that bias immunity to the most effective type of T cell response or antibody isotype, or that promote optimal virus antigen uptake, processing, and presentation to T cells. Dendritic cells (DC) play a key role in both the innate and adaptive responses, but can also initiate tolerogenic responses. A better understanding of DC subsets, costimulatory molecules, and signaling pathways is needed to optimally define immune mechanisms of virus control.  Examples of research in this area include, but are not limited to:

Mucosal immunity. Many viruses cause primarily respiratory, gastrointestinal, or urogenital infection, and variant strains may differ in their site of entry, tissue or cellular tropisms, and their capacity to injure particular tissues. Mucosal epithelial cells comprise the initial barrier to pathogen entry and mucosal tissues differ greatly in terms of their local environment and susceptibility to colonization and infection. There is little comprehensive information on the recognition of viruses and the development of protective immunity within the mucosa. The innate immune detection of viruses by PRRs in the mucosal system is not well understood, but will depend on the route of entry of the virus and the cells or tissues that are infected.  Adaptive immunity in the mucosal systems is similar to that seen in other parts of the body, but there are populations of specialized cells that function in mucosal immunity. Specialized DC and M cells appear to play a key role in tolerance to commensal organisms, but their function in anti-virus immunity is not clear. A discrete population of CD8 T cells, the intraepithelial lymphocytes, may interface directly with viruses in mucosal tissues. The role of B cells in mucosal immunity includes not only the production of IgM and IgG, but also of secretory IgA, which provides protective functions such as virus neutralization and formation of antigen-antibody complexes to block entry of viruses across epithelial barriers. The mucosal tissues of the respiratory, gastrointestinal, and urogenital systems differ in many regards, such as architecture, APC types, the viruses and antigens likely to be encountered, and their capacity to release specific cytokines and chemokines. Furthermore, the presence of additional factors such as surfactants and mucosal enzymes, as well as pH and redox variation in mucosal sites, may influence the local immune response and the stability or degradation of soluble mediators, cytokines, adjuvants, and other vaccine components. It will be important to understand the processes that initiate and regulate innate and adaptive immunity in response to viruses in the mucosal sites that serve as major entry points of infectious pathogens.  Examples of research in this area include, but are not limited to:

Immune memory. Both natural infection and vaccination may result in long term protection against subsequent exposure to the same virus, or closely related viruses, due to the generation and maintenance of long term immune memory.  Although virus infections generally stimulate strong innate immune responses that should lead to robust adaptive immunity, some infections cause T cells to become unresponsive and unable to develop an effective memory repertoire.  In addition, the roles that innate immunity and virus evasion factors play in the development of memory remains an area that requires further exploration.  Examples of research in this area include, but are not limited to:

Protective antibody responses.  Studies of virus specific B cell activation and the production of protective antibodies are especially encouraged in this FOA.  Antibodies are thought to provide primary protection after vaccination or re-infection with the same virus. However, much of the basic work in model systems has focused on T cell responses, with insufficient investigation of B cell responses or the interdependence of T and B cell regulation. Examples of research in this area include, but are not limited to:

Immunity in vulnerable subpopulations. Immune function and the ability to generate protective immune responses vary with age and underlying health status. Elderly people have a limited repertoire of memory T cells that appear to be functionally compromised as compared to those of young adults.  In adults, thymic output of naïve T cells and bone marrow production of new B cells decline with age, resulting in limited repertoires of memory cells to pathogens, including viruses. Very young children have a naïve repertoire of T cells and may lack significant memory responses. Many chronic diseases involve immune dysfunction or require treatments that cause immunodepletion or immunosuppression, including conditions such as transplantation, cancer, or autoimmune diseases. These conditions are characterized by heightened susceptibility to infection or altered requirements for successful vaccination. In other instances, there are major differences among populations in susceptibility to, natural history of, and response to therapy of certain infectious diseases.  Identification of differences in virus immunity may facilitate more effective vaccination strategies and treatment modalities.  Examples of research in this area include, but are not limited to:

The following research areas will be considered non-responsive by institute program staff, and the applications proposing to do the studies in the following areas will not be reviewed.

All applications MUST propose studies on at least one NIAID Category A, B, or C or Emerging/Re-emerging virus (see list at http://www3.niaid.nih.gov/research/topics/emerging/list.htm). Studies on other viruses important to human health may also be included. However, at least one of the specific aims in U01 grants and one of the projects proposed in U19 grants must be solely dedicated to viruses on the list of NIAID Category A, B, or C or other Emerging/Re-emerging virus(es). Although clinical trials are excluded, viral challenge studies in humans may be proposed.  For further information, see the “Other Submission Requirements” Section (IV-6). 

Steering Committee

A network of synergistic Immune Mechanisms of Virus Control (IMVC) centers will be established through this program to enable multidisciplinary approaches to advance this area of research. The IMVC network will be governed by a Steering Committee to coordinate and facilitate research activities for the overall program, and to ensure optimal research flexibility, synergy, and efficiency. The Steering Committee will include the Principal Investigators from all awarded IMVC U01 and U19 cooperative agreements.

IMVC members will cooperate within the program to share resources, methods, and data to facilitate progress. The network investigators will also be provided opportunities to access resources from other NIAID-funded programs and to collaborate on research projects as appropriate. All research groups will share responsibility for program development and resource coordination through the IMVC Steering Committee that will be established upon award of the grants. When appropriate, and in accordance with NIH policies (http://grants.nih.gov/grants/policy/data_sharing and http://www.ott.nih.gov/policy/rt_guide_final.html), U01 and U19 awardees will be expected to collaborate; share novel reagents, assays, animal models, and human samples; and share both positive and negative results that would help guide the research activities of other IMVC network members. The NIAID, in concert with the IMVC Steering Committee, will have the option to redirect research activities within IMVC grants if it is considered beneficial to the overall program.

IMVC Annual Meetings

Principal Investigators must participate in a kickoff meeting soon after award, as well as meetings to be held annually thereafter. These meetings will be organized by the NIAID in order to: share both positive and negative results; share materials including reagents and techniques; evaluate progress; and identify new research opportunities. In the application, budget requests must include costs for attendance of the Principal Investigator and up to 6 other relevant staff to attend the kickoff meeting and the annual meetings.  These meetings will convene in Bethesda, Maryland.

Discretionary Funds

NIAID plans to set aside approximately $1 million per year in discretionary funds to support exploratory pilot research projects and/or research resource development projects to capitalize on emerging opportunities. After award, NIAID will transfer discretionary funds to a single IMVC institution to be responsible for disbursement, management, and reporting on discretionary fund projects approved by the Steering Committee.  Discretionary funds may also be used for the development, production, characterization, and distribution of shared reagents, shared resources, or access to a unique resource such as a nonhuman primate facility. The Steering Committee will establish goals, priorities, and evaluation criteria for the use of the discretionary funds to support pilot research or research resource development or utilization.  PIs awarded under this FOA will have an opportunity to compete for the discretionary funds. The expenditures of discretionary funds will be restricted until a process for the prioritization, solicitation, and evaluation of proposals and the disbursement of funds is established and agreed upon in writing by the Steering Committee.  Once this process is established, funds will be available for distribution.

Milestones of Progress

This program is milestone-based, and annual funding will depend on progress and meeting milestones negotiated in the previous year.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NIH Research Project Cooperative Agreement (U01) and NIH Multi-Project Cooperative Agreement (U19) award mechanisms.  The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

This FOA is a one-time solicitation.

2. Funds Available

The estimated amount of funds available for support of 7-15 projects awarded as a result of this announcement is $14 million for fiscal year 2009.  An additional $1 million will be available in a Discretionary Fund to support exploratory pilot research projects that propose projects that capitalize on emerging opportunities.  Future year amounts will depend on annual appropriations.  Although the size of award may vary with the scope of research proposed, direct costs (excluding third party F&A) are expected to range from $250,000 to $500,000 per year for U01 grants, and $750,000 to $1.5 million per year for U19 grants.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewal applications will not be permitted in response to this FOA.

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired:  TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Applicants should follow PHS398 instructions when preparing single project applications (U01). Additional instructions are required for the preparation of multi-project applications (U19) because the PHS Form 398 is designed primarily for individual, free-standing research grant (R01) applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. 

Supplemental Instructions for the Preparation of Multi-Project Applications

The following section supplements the instructions found in the PHS Form 398 for preparing multi-project grant applications that will be submitted in paper format. Additional instructions are required because the PHS Form 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme.

The supplemental instructions below are divided as follows:

A.   General Instructions – addresses collaborative efforts among research projects, the administrative and organizational structure, as well as the overall facilities and environment, and the overall budget.

B.   Specific Instructions for Individual Projects – describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

C.   Specific Instructions for Core Units – Cores must provide services or resources to support at least two research projects. Instructions describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

A.   General Instructions

All applications must be submitted on PHS Form 398. The multi-project grant application should be assembled and paginated as one complete document.

1.   Form Page 1 - Face Page

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

2.      Form Page 2

Using Form Page 2 of the PHS 398, provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator(s) of the multi-project application, followed by the Project Leaders of the component research projects and cores, other key personnel, and then other significant contributors.

3.      Form Page 3 - Table of Contents

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g., Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g., Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4.      Composite Budget

Do not use Form Page 4 of the PHS 398. Instead, using the suggested format presented below, prepare a composite budget for all proposed years of support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component

Year 1

Year 2

Year 3

Year 4

Year 5

All Years

Project 1. Invest.

125,000

130,000

135,200

140,608

146,232

677,040

Project 2. Study

125,000

130,000

135,200

140,608

146,232

677,040

Project 3. Develop.

100,000

104,000

108,160

112,486

116,985

541,631

Core A. Admin. Core.

50,000

52,000

54,080

56,243

58,493

270,816

Core B. DNA

25,000

50,000

52,000

54,080

56,243

237,323

Totals

425,000

466,000

484,640

504,025

524,185

2,403,850












5.      Form Page 5

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry.

6.      Biographical Sketch Format Page

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the Principal Investigator first, followed by those of other key personnel in alphabetical order.

7.      Other Support Format Page

Do not complete. (Any required information will be requested from successful applicants prior to grant award.)

8.      Resources Format Page

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

9.      Program Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 25 pages. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

10. Checklist

One Checklist, placed at the end of the application, is to be submitted for the entire application. Individual research projects and cores do not require a checklist.

B.   Specific Instructions for Individual Research Projects

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research project.

1.   Cover Page

The Face Page of the PHS 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project. This Cover Page will demarcate each individual research project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

Project Number and Title:  (e.g., 1. Immune Mechanisms of Virus Control)

Name of Project Leader:  (e.g., Jones, Roberta A.)

Human Subjects: (Yes or No)

If Yes, exemption number:

(or)

IRB Approval Date: (e.g., 12/13/2006,or "Pending")

(and)

Federalwide Assurance (FWA) number:

Vertebrate Animals: (Yes or No)

If Yes, IACUC Approval Date: (e.g., 11/17/2006, or Pending)

(and)

Animal welfare assurance number:

Proposed Period of Support:

From: (mmddyy - e.g., 07/01/2007)

To: (mmddyy - e.g., 06/30/2112)

Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)

Direct Costs: (e.g., $150,000)

Total Costs: (e.g., $162,000)

Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)

Direct Costs: $700,000

Applicant Organization:

(full address)

2.   Form Page 2

Provide a Description (abstract) of the research proposed in the project according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the research project will contribute towards attainment of the multi-project program objectives.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

3.      Form Page 3

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

4.      Biographical Sketches

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

5.      Research Plan (Items 2-5 cannot exceed 25 pages)

Item 2 -- Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the project's relationship to the multi-project program goals and how it relates to other projects or cores. This section is typically one page.

Item 3 -- Background and Significance: Use this section to describe how the proposed research will contribute to meeting the program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

6.     Milestones and Timeline  (Additional 5 pages)

Use this section to include a description of the yearly milestones that will be met by the proposed work and a corresponding timeline. This section is to follow the Research Plan and will not be counted in the page limit for the Research Plan.

7.     External Scientific Advisory Group (ESAG)  (Additional 1 page)

Applicants may propose to include an external advisory group.  Specific potential members of the proposed ESAG should NOT be named in the application and ESAG candidates should NOT be recruited or contacted prior to review and award.  However, applicants may propose a plan describing the expertise needed for the external advisory group and descriptions of the types of individuals who would be asked to become advisory board members.  The applicant should explain the duties of the group and include costs for meetings of the group within the proposed budget.  This section is to follow the Milestones and Timeline and will not be counted in the page limit for the Research Plan.

8.     If Applicable: Virus Challenge Study  (Additional 10 pages)

All virus challenge projects must provide a detailed concept proposal, as detailed in section IV-6 (Other Submission Requirements and Information).

9.     Appendix

Do not create an appendix for an individual project.

C.   Specific Instructions for Cores

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

1.      Cover Page

The Face Page of the PHS 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

Core Letter and Core Title:  (e.g., A. Monoclonal Antibody Production Core)

Name of Core Leader:  (e.g., Smith, Robert A.)

Human Subjects (Yes or No)

If Yes, Exemption Number

(or)

IRB Approval Date (e.g., 5/14/06, or Pending)

(and)

Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)

If Yes, IACUC Approval Date (e.g., 4/15/07, or Pending)

(and) Animal welfare assurance number

Proposed Period of Support

From: (mmddyy, e.g., 07/01/2007)

To: (mmddyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period

(e.g., Direct Costs: $50,000)

(e.g., Total Costs: $70,000)

Costs Requested for the Entire Budget Period

(e.g., Direct Costs: $212,323)

(e.g., Total Costs: $297,252)

Applicant Organization

(full address)

2.      Form Page 2

Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the multi-project program objectives.

List the performance sites where the core activities and services will be conducted.

Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

3.      Form Page 3

Prepare a Table of Contents for the core using Form Page 3 of the PHS 398.

4.      Biographical Sketches

Do not repeat the biographical sketches of participating investigators since this information will be located at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

5.   Core Research Plan (Items 2-5 cannot exceed 25 pages)

Item 2 -- Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the project's relationship to the multi-project program goals and how it relates to other projects or cores. This section is typically one page.

Item 3 -- Background and Significance: Use this section to describe how the proposed research will contribute to meeting the program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

Foreign Organizations (Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

In addition, for applications from foreign organizations:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: July 18, 2008
Application Receipt Date: August 18, 2008
Peer Review Date: January, 2009
Council Review Date: January, 2009
Earliest Anticipated Start Date: March, 2009

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Barney Duane Price, PhD
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3139, MSC-7616 
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 451-2592
FAX: (301) 480-2408
Email: pricebd@niaid.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).


At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Barney Duane Price, PhD
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3139, MSC-7616 
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 451-2592
FAX: (301) 480-2408
Email: pricebd@niaid.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements and Information

Essential elements of the U01 include: (1) a single Research Project that may include consortium agreements, but does not include Core resources and facilities as defined below for U19 applications; (2) a single Principal Investigator who will be scientifically and administratively responsible for the research project; and (3) a single applicant institution that will be legally and financially responsible for the use and disposition of funds awarded.

Essential elements of the U19 include: (1) a minimum of two interrelated Research Projects organized around a central theme; (2) collaborative efforts and interactions among these independent projects and their investigators to achieve a common goal; (3) a single Principal Investigator who will be scientifically and administratively responsible for the group effort; (4) a single applicant institution that will be legally and financially responsible for the use and disposition of funds awarded; and (5) support provided, as necessary, for Scientific Core resources or facilities, each of which is expected to be utilized by at least two Research Projects in order to facilitate the research effort. Lack of synergy and interaction among the Research Projects and Scientific Cores will adversely affect the priority score of a U19 application, even if the Scientific and Technical merit of individual projects is high.  In addition, it is strongly recommended that an Administrative Core be proposed in U19 grant proposals.

Research in Animal Models:  If animal studies are proposed, they must be well justified in terms of their relevance to human infection.

Milestones and Timeline:  All applicants should include a description of the yearly milestones that will be met by the proposed work and a corresponding timeline (may not exceed 5 pages). This section is to follow the Research Plan for each project, but will not be counted in the page limit for the Research Plan. It should include a detailed description of the milestones to be met each year, the criteria to be used to evaluate the satisfactory completion of each milestone, and a timeline to achieve the goals and milestones of the project. It is recognized that milestones may require revision and re-negotiation during the course of the project period.

External Scientific Advisory Group (ESAG):  Applicants may propose to include an external advisory group.  Specific potential members of the proposed ESAG should NOT be named in the application and ESAG candidates should NOT be recruited or contacted prior to review and award. However, applicants may propose a plan describing the expertise of the external advisory group and descriptions of the types of individuals who would be asked to become advisory board members. The applicant should explain the duties of the group, and include costs for meetings of the group within the proposed budget.   This section should be no longer than one page and should follow the Milestones and Timeline section.  It will not be counted in the page limit for the Research Plan.

Steering Committee: A Steering Committee will be established to serve as the governing board of the IMVC program.  The Committee will be comprised of the PD/PI of each U01 and U19 grant and the NIH Project Scientist, and may also include other individuals with expertise in the scientific areas, as well as Program Officials from the NIAID Division of Microbiology and Infectious Diseases.  The PD/PI from each U01 and U19 grant will be a member of the Steering Committee and each will have one vote.  The NIH Project Scientist will serve as a non-voting member of the Steering Committee.  Awardees will be required to accept and implement policies approved by the Steering Committee.

IMVC Meetings: Principal Investigators must participate in a kickoff meeting soon after award, as well as meetings to be held annually thereafter. These meetings will be organized by the NIAID in order to: share both positive and negative results; share materials including reagents and techniques; evaluate progress; and identify new research opportunities. In the application, budget requests must include costs for attendance of the Principal Investigator and up to 6 other relevant staff to attend the kickoff meeting and the annual meetings.

Cooperative Agreement Terms and Conditions of Award: All grantees must agree to these conditions; see Section VI.2.A.

Virus Challenge Studies in Humans: All applications proposing a virus challenge study in humans MUST include the following information:

Concept Proposal:  All virus challenge projects must provide a single detailed concept proposal addressing the following aspects of the proposed study (an additional 10 pages will be allowed for the Concept Proposal and will not count against the 25 page limit for the Research Plan; per U01 and per project in a U19 application.  The Concept Proposal should address the following categories:

1.      Study title

2.      Hypothesis to be tested

3.      Study objectives

4.      Population

5.      Clinical sites

6.      Provision of challenge virus stock

7.      Description of challenge virus stock being used

8.      Regimen

9.      Study design

a.      Eligibility/exclusion criteria

b.      Number of subjects

c.       Anticipated duration of recruitment phase

d.      Total study duration

e.      Primary endpoints/outcomes

f.        Secondary endpoints/outcomes

g.      Study visit schedule and primary evaluations, including laboratory evaluations

h.      Sample size justification

i.         Any proposed sub-studies

j.        Statistical analyses and data analyses plan

10.  Plan for monitoring safety

In addition, the following information must also be provided in the Protection of Human Subjects section of the application:

1. A plan for the management of the challenge study that includes collection, storage, management, quality control, and reporting of study data and a system for adverse event reporting.

2. A description of the procedures and timeline for study development and implementation.

3. A plan for the recruitment and retention of study participants.  In addition, the application must describe the overall approaches to overcoming obstacles and limitations with respect to these activities.

4.  A copy of the Informed Consent document.

5.  A copy of the Investigator’s Brochure for any licensed vaccine to be used in the study, if applicable.

Applications that propose virus challenge studies but lack a Concept Proposal detailed as described above will be returned to the applicant without review.

Research Plan Page Limitations

Not applicable

Appendix Materials

All paper PHS 398 applications submitted for May 25, 2008 and subsequent due dates must provide appendix material on CD only, and include five identical CDs in the same package with the application.  Paper applications submitted for due dates prior to May 25, 2008 may voluntarily provide the appendix on five identical CDs; if submitting CDs it is not necessary to include a paper appendix. (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Review Criteria for Individual Research Projects (U01 and U19)

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?  

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  

In addition to the above review criteria, the following criteria will be applied to multi- project (U19) applications in the determination of scientific merit and the priority score.

Review Criteria for Cores (U19)

Administrative Core

Scientific Research Cores

Review Criteria for the Overall Application (U19)

The following items will be considered in the determination of overall scientific merit and priority score for the entire application:

Overall score: a single numerical priority score will be assigned to the whole application after consideration of all of the elements.  The overall score for the application will be based primarily on the scientific merit of the individual components, with additional consideration of the overall synergy and integration of the components, the overall program organization, and the capabilities of the associated personnel.

If peer reviewers deem that fewer than the required two research projects have substantial and significant merit, the entire application is no longer a viable program and will not be scored.

Review criteria for the overall application:

Review Criteria for a Concept Proposal for a Virus Challenge Study in Humans

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

Biohazards/Select Agent Research: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

Milestones and Timelines: The appropriateness and feasibility of the proposed milestones and timeline.  The priority score should not be affected by the evaluation of the Milestones and Timeline.

External Scientific Advisory Group:  The appropriateness of the plan to utilize an External Scientific Advisory Group, if proposed.  The priority score should not be affected by the evaluation of the External Scientific Advisory Group plan.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources.  However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA.  Program staff within the IC will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

Not applicable.

Section VI. Award Administration Information


1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page).

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. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. 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 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 (U01) or (U19), "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.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining the research plan and goals; overseeing/performing the scientific activities of the plan; monitoring the accomplishment of successful completion of milestones within the timeframe and budget proposed; cooperating with NIAID programmatic, technical, and administrative staff; and administratively managing the U01 or U19. Each Principal Investigator will be a voting member of the Steering Committee, will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. However, awardees must be committed to making research samples and tools, methods, data, and materials that they develop under the IMVC program available to other IMVC centers and the research community.

NIAID policy requires that clinical research studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIAID policy was published in the NIH Guide on July 12, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

All clinical research activities performed under this award must be in compliance with all U.S. Federal regulations, guidance and NIH policies applying to the conduct of research involving human subjects and regulatory application for new drug or biological licenses when applicable. These include, but are not limited to, U.S. Code of Federal Regulations (CFR) Title 21, Parts 11, 50, 54, 56, 312, 314, 601 and Title 45, Part 46; ICH guidance for Good Clinical Practice (GCP); and NIH grants policy (refer to http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). In addition, the Awardee must assure that all sites in the U.S. and outside the U.S. comply with the following:

a. Each institution engaged in human subjects research has a current, approved Assurance Number on file with the DHHS Office for Human Research Protections (OHRP).

b. Each protocol and informed consent document is approved by the responsible Institutional Review Board (IRB)/Ethics Committee (EC) prior to subject entry.

c. Each study investigator and sub-investigator has provided a current curriculum vitae to NIAID.

d. Each study participant (or legal representative) will sign an IRB/EC-approved protocol consent prior to entry on study as part of the Informed Consent Process.

All clinical research activities performed outside of the U.S. must, in addition to U.S. Federal regulations, comply with the host country regulations for human subjects.

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. A program official from the extramural NIAID Basic Immunology Branch of the Division of Allergy, Immunology, and Transplantation will serve as NIH Project Scientist for the IMVC program. In conjunction with other NIAID scientific program staff and the IMVC Steering Committee (see below), the Project Scientist will provide advice and guidance on technical issues, such as reviewing progress or recommending changes. Administrative assistance will be provided by the NIH Project Scientist in conjunction with the NIAID Grants Management Office.  The NIH Project Scientist may also: participate in the design of activities; advise in the selection of sources or resources (e.g. determining where a particular reagent may be found); coordinate or participate in the collection and/or analysis of data; or advise in the management and technical performance.

The NIH Project Scientist will serve as a non-voting member of the Steering Committee, schedule the meetings and teleconferences of the Steering Committee, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.

The NIH Project Scientist, together with the Steering Committee, will review the performance of each participating IMVC through consideration of annual reports, site visits, and compliance with Steering Committee procedures.  

Additionally, an NIAID Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the Notice of Grant Award.  The assigned Program Officer may also serve as the NIH Project Scientist.

2.A.3.  Collaborative Responsibilities

IMVC Steering Committee

A Steering Committee will be established to serve as the governing board of the IMVC program.  The Committee will be comprised of the PD/PI of each U01 and U19 grant and the NIH Project Scientist, and may also include other individuals with expertise in the scientific areas, as well as Program Officials from the NIAID Division of Microbiology and Infectious Diseases.  The PD/PI from each U01 and U19 grant will be a member of the Steering Committee and each will have one vote.  The NIH Project Scientist will serve as a non-voting member of the Steering Committee.  Awardees will be required to accept and implement policies approved by the Steering Committee.

The IMVC Steering Committee will meet quarterly by teleconference, except for one yearly face-to-face meeting in conjunction with the annual Scientific Meeting.  A Steering Committee Chair will be elected by majority vote from among the U01 and U19 PD/PIs at the first Steering Committee meeting. 

The responsibilities of the IMVC Steering Committee include the following:

NIAID intends to support the peer-reviewed studies proposed in the awarded grant applications.  However, under special circumstances, the Steering Committee will establish guidelines and review procedures to evaluate and determine opportunities for redirection or modification of the peer-reviewed projects.

Steering Committee Meetings

NIAID will arrange quarterly Steering Committee teleconferences, and annual face-to-face meetings in conjunction with the annual IMVC scientific meeting. All Steering Committee members must agree to participate in the quarterly teleconferences and annual face-to-face meetings.

Discretionary Fund

NIAID plans to set aside approximately $1 million per year for a discretionary fund for new projects. These funds will be available for new projects (approved by the Steering Committee) on emerging opportunities to discover new immune mechanisms as they relate to viral infections and vaccines. Other examples could include the development, production, characterization, and distribution of shared reagents, shared resources, or access to unique resources, such as nonhuman primate facilities.

The Steering Committee will establish guidelines for the disbursal of discretionary funds. These guidelines will include a process for:

After award, NIAID will transfer the discretionary funds to one IMVC institution that will be responsible for disbursement, management, and reporting on the use of discretionary funds as approved by the Steering Committee. Discretionary fund expenditures will be restricted until a process for the prioritization, solicitation, and evaluation of proposals and the disbursement of funds is established and agreed upon in writing by the Steering Committee. Once this process is established, funds will be available for distribution.

Scientific Meetings

Each IMVC Awardee will participate in a kickoff meeting of all IMVC centers to be held soon after award in the Bethesda, MD area, and will participate in scientific meetings to be held annually thereafter. All Principal Investigators are required to attend these meetings, together with additional scientific staff from their IMVC when appropriate. All travel costs will be borne by the Principal Investigators. The annual IMVC scientific meeting is open to the members of the IMVC program and NIH extramural staff, and is a forum for members to provide the latest update on their research, exchange ideas and information, and discuss collaborations among IMVC members. Meeting participants will identify the group's tangible resources, capabilities, and needs to advance overall IMVC goals. The Principal Investigator of each IMVC is required to make an oral presentation on current and planned activities and projects. For planning purposes, assume that the two-day scientific meeting will be held each year in the Bethesda, MD area.  

2.A.4. Arbitration Process

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 arbitration. An Arbitration 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Annual progress reports shall be submitted electronically through eSNAP. The progress report shall follow the general format for annual progress reports for NIH grant applications. In addition, an executive summary and a detailed description of the work done to achieve the specific milestones for that funding year shall be included. If milestones have not been met, an explanation of what has been accomplished and the alternatives, solutions, and/or problems that exist must be provided. If the milestones need to be modified, updated milestones and associated timelines should be included in the report and reviewed with the Program Officer. The Program Officer in conjunction with the Steering Committee will determine if major changes are appropriate and provide approval.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Lara R. Miller
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Room 3002, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601

Telephone: (301) 496-7551
FAX: (301) 480-2381
Email: lrmiller@niaid.nih.gov 

2. Peer Review Contacts:

Barney Duane Price, PhD
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3139, MSC-7616 
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 451-2592
FAX: (301) 480-2408
Email: pricebd@niaid.nih.gov

3. Financial or Grants Management Contacts:

Michael Fato
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 2123, MSC-7614
6700B Rockledge Drive
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Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


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