NIH's new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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

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

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

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), supports extramural research focused on understanding, controlling and preventing diseases caused by virtually all infectious agents. In response to threats presented by emerging infectious diseases and bioterrorism, the NIAID Division of Microbiology and Infectious Diseases (DMID) has established complementary research programs to facilitate development of medical countermeasures for certain pathogens and toxins.

This FOA solicits applications to continue the Centers of Excellence for Translational Research (CETR) program focused on the development of medical countermeasures and associated platforms/technologies targeting select NIAID Emerging Infectious Diseases/Pathogens. For the purposes of this FOA, "translational research" is defined as research and developmental activities focused on transforming basic science outcomes (knowledge, technologies, infrastructure, etc.) into new and innovative approaches for prevention, diagnosis, and treatment of disease. Emphasis will be placed on Centers that integrate current research knowledge and infrastructure with highly innovative and synergistic approaches to facilitate medical countermeasure development, and address related constraints, challenges or barriers to product development, licensure and usage. Priority will be given to Centers that address the greatest clinical need.

The NIH and other agencies in the Department of Health and Human Services (DHHS) support development of countermeasures to protect the public from infectious diseases. In 2002, the NIH advanced strategic plans to counter threats presented by emerging and re-emerging infectious diseases. A significant component of these plans was the NIAID Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) program, which enabled appropriate infrastructure and multifaceted research and development activities to provide scientific information and translational research capacity to facilitate discovery and development of the next generation of therapeutics, vaccines, and diagnostics. In 2014, NIAID transitioned the RCE program to the CETR program to facilitate innovative, interdisciplinary translational research efforts focused on countermeasure and/or related platform development. The initial and continuing goal of the CETR program is to advance the discovery and/or development (or availability) of new and improved countermeasures or related technologies specific to select NIAID Emerging Infectious Diseases/Pathogens. This FOA reflects current priorities outlined in the 2013 NIAID Strategic Plan, the 2016 HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan, the National Strategy for Combating Antibiotic-Resistant Bacteria (CARB), the National Action Plan for Combating Multi-drug Resistant Tuberculosis, the HHS 2010 Medical Countermeasure Enterprise Review, and Homeland Security Presidential Directive 18: Medical Countermeasures against Weapons of Mass Destruction.

The objective of this FOA is to continue a program of multi-project translational research Centers focused on advancing discovery, preclinical development, production, licensure and/or use of new or improved countermeasures (therapeutics, immunotherapeutics, vaccines, vaccine technologies, and medical diagnostics) or related technologies specific to select NIAID Emerging Infectious Diseases/Pathogens. NIAID encourages Centers focused on development of medical countermeasures that are effective against a variety of pathogens and toxins, technologies that can be widely applied to improve classes of products, and platforms that can reduce the time and cost of creating new products.

Each Center will be organized around a Center-selected theme (Center theme) that addresses development and/or use of a targeted countermeasure or technology. NIAID anticipates considerable variety among Center themes and objectives, which can range from the development of single or multiple countermeasures targeting a specific group of listed pathogens/toxins to the development of new technologies or platforms that target a wide array of pathogens/toxins. Translational activities are anticipated to range from very early discovery-based efforts to late-stage preclinical development with industrial participation. Additionally, each Center will consider and address anticipated regulatory barriers for the targeted countermeasure or technology, particularly for new classes of medical countermeasures for which there are no precedents for FDA approval.

Examples of translational Center themes include, but are not limited to, the following areas:

• New or improved therapeutic(s) against antimicrobial-resistant pathogens.
• Development of a multivalent (e.g. broadly cross-protective or "universal") vaccine.
• Host-targeted interventions as therapeutics.
• Development of broad-spectrum countermeasures against taxonomically-related viruses.
• New or improved vaccine technologies or production platforms.
• Development of a broad-spectrum countermeasure technology.
• Co-development of a new therapeutic and associated diagnostic.

Note: For the purpose of this FOA, "preclinical" is defined as all activities beyond lead candidate identification or technology/platform/prototype development.

Note: For the purpose of this FOA, "broad-spectrum" is defined as a countermeasure which is effective against multiple infectious disease agents where one or more is a targeted select NIAID Emerging Infectious Diseases/Pathogen.

Note: Center themes supported by this program must target select NIAID Emerging Infectious Diseases/Pathogens (see below). Accordingly, all Center research and development activities must utilize the virulent form of a listed human pathogen under appropriate biosafety conditions, or a CDC-approved excluded strain that is an attenuated form of the human pathogen.

Note: While Clinical development strategies and/or clinical studies (e.g. sample collection, strain isolation, etc.) may be included within an overall project, clinical trials will not be supported. Utilization of human-derived material in pre-clinical studies is encouraged.

To be responsive to this FOA, applications must focus on translational activities towards development of one or more specific countermeasures or technologies described below.

Therapeutics

This program will support discovery and/or development of new or improved therapeutics against select NIAID Emerging Infectious Diseases/Pathogens (antimicrobial-resistant bacteria/fungi and emerging viral pathogens; see below), including immune-based and host-targeted forms. Encouraged are broad-spectrum therapeutics or those targeting pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern. Therapeutics of interest include small molecules, biopharmaceuticals, nucleic acids, or peptides to be used as monotherapy or in combination with other drugs or as adjunctive therapy.

Immune-based therapeutic projects may focus on broad-spectrum or pathogen- or toxin-specific immunotherapeutics. Of interest are immunotherapeutics that would prevent infection or intoxication from an immediate threat or post-exposure treatment to suppress infection and disease. NIAID encourages development of immunotherapeutics that directly affect pathogens and/or therapeutic approaches that stimulate non-specific immunity. Passively administered therapeutics, including those that can be delivered via an intramuscular injection, may be especially valuable to respond to the initial outbreak of an infectious agent and may complement the use of existing antimicrobial drugs or vaccination programs.

The development of therapeutics that target host-encoded functions provides a potential solution to the emergence of microbial resistance and high developmental costs associated with treatments effective against only one microbe. Accordingly, NIAID encourages the development of therapeutics that target specific host functions and/or pathways required for infection and pathogenesis by unrelated pathogens. Host-targeted therapeutic projects will focus on a host-encoded function required for infection, replication, spread and/or pathogenesis by one or more listed pathogens (see below) and potentially, additional non-listed pathogens. Applicants must clearly identify the specific host-pathogen interaction(s) that correspond to the therapeutic(s) targeted for development.

Of importance for novel host-targeted therapeutics is consideration of proposed work that directly addresses the clinical and regulatory pathway to product registration and potential hurdles such as demonstration of pathogen susceptibility and therapeutic efficacy using non-standard in vitro assays and in vivo disease models, as well as potential toxicity issues.

Note: A broad-spectrum therapeutic is defined as a therapeutic agent that targets a common, invariable, or essential component of different strains or classes of microbes, or one that targets a host function required for infection and/or disease.

Note: Projects proposing the development of a host-targeted therapeutic that acts primarily by stimulating the host immune response through direct regulation of interferon expression will be considered non-responsive to this FOA.

Note: This FOA will not support repurposing of a FDA-approved drug.

Therapeutics categories supported by this program include, but are not limited to, narrow-spectrum drugs, broad-spectrum drugs, immunotherapeutics, host-targeted therapeutics, innovative therapeutic approaches/strategies, drugs targeting novel mechanisms, or adjunctive therapeutics. Therapeutics projects supported by this FOA must address one of the following select pathogen categories:

Antimicrobial-Resistant Bacteria/Fungi

This program will support development of new or improved therapeutics for select pathogens for which drug resistance poses a significant public health concern. Responsive projects must target at least one pathogen listed in the Centers for Disease Control and Prevention's Antibiotic Resistance Threats in the United States, 2013 report.

Emerging Viral Pathogens

This program will support development of new or improved therapeutics for emerging viral pathogens of public health concern. Responsive applications must target at least one viral pathogen on the NIAID Emerging Infectious Diseases/Pathogens list.

Vaccines

This program will support discovery and/or development of vaccines (including immunoprophylactics) against emerging pathogens, focusing on multivalent/universal forms, vaccines targeting specific pathogens, and related vaccine technologies (see below). For the purpose of this FOA, "immunoprophylactic" is defined as an antibody, antibody cocktail, related antibody product or other biologic that is efficacious when provided prophylactically.

Vaccine projects supported by this FOA must align with one of the following categories:

Multivalent/Universal Vaccines

Multivalent or universal vaccines are defined as broad-spectrum vaccines that provide protection against a group of taxonomically-related pathogens, or two or more unrelated pathogens. Vaccines characterized by broad-spectrum activity in this class include cross-protective forms, which induce an immune response against constant components of two or more microbes, and multiple component forms, which include elements that protect against microbes that are different, and may or may not be related. Examples of this vaccine category include, but are not limited to, a universal influenza vaccine or a multivalent vaccine that protects against multiple flaviviruses.

Vaccines Against Antimicrobial-Resistant Bacteria/Fungi

This program will support development of vaccines targeting select bacterial/fungal pathogens for which drug resistance poses a significant public health concern. Responsive projects must target at least one pathogen listed in the Centers for Disease Control and Prevention's Antibiotic Resistance Threats in the United States, 2013 report.

Vaccines Against Select Emerging Viruses

This program will support development of candidate vaccines targeting emerging viral pathogens of public health concern. Responsive projects must target at least one viral pathogen listed in the World Health Organization Priority Diseases Needing R&D Actions, 2017 revision.

Vaccine Technologies

This program will support Center activities focused on discovery and/or development of innovative vaccine technologies (including adjuvants), particularly those that would improve vaccine effectiveness and/or simplify vaccine delivery to patient populations during a natural outbreak of an infectious disease or following the intentional release of an agent. Proposed projects will pair the candidate technology with one or more appropriately mature, well-characterized vaccine(s)/antigen(s) (except those pertinent to HIV) for which models and assays exist to allow evaluation of the technology. Applications focused on development of technologies such as delivery platforms, antigen targeting, adjuvants, stability and cold-chain minimization, production characterization or formulation methodologies are encouraged.

Note: The development of vaccines against Mycobacterium tuberculosis is currently supported under separate and specific funding opportunities. Accordingly, projects focused on development of a vaccine against Mycobacterium tuberculosis will be considered non-responsive to this FOA.

This program will support development of new and innovative integrated, rapid, easy-to-use, sensitive, culture-independent, sample-to-answer, diagnostic platforms and/or technologies that identify select antimicrobial-resistant bacterial pathogens and determine their antimicrobial susceptibility and/or resistance. Responsive platforms/technologies must target one or more pathogens listed in the Centers for Disease Control and Prevention's Antibiotic Resistance Threats in the United States, 2013 report. Proposed platforms should be intended for use in clinical settings, including hospital-based clinical microbiology laboratories, point-of-care, and/or public health laboratories. These diagnostics will be developed to enable clinicians to rapidly provide appropriate therapy to infected patients and/or facilitate clinical trial enrollment for new candidate therapeutics.

For the targeted pathogen(s), the proposed diagnostic platform should be supported by proof-of-concept data demonstrating feasibility and must exceed performance specifications of currently available instruments/systems. Additionally, projects should address all pertinent components of platform design and development (e.g. assay and prototype development/optimization, sample preparation, sample processing, component integration, software development, process development, manufacturing, and diagnostic validation). While it is not expected that proof-of-concept stage technologies should be ready for validation studies to enable FDA clearance or approval at the end of the project period, FDA clearance or approval would be an eventual long-term goal of projects supported under this program.

The following technologies/platforms are strongly encouraged:

• Multiplex diagnostic technologies;
• Technologies capable of identifying engineered or otherwise acquired genetic traits, such as patterns of antimicrobial resistance or enhanced virulence; and/or
• Technologies that could be operational in non-traditional health care settings including rural and urban community health care clinics and temporary health care clinics (e.g., those established in response to a natural or deliberate outbreak).

The proposed diagnostic platform must:

• Detect one or more bacterial pathogens listed in the Centers for Disease Control and Prevention's Antibiotic Resistance Threats in the United States, 2013 report;
• Provide phenotypic information about corresponding drug-susceptibility and/or drug-resistance that will inform clinical therapeutic approaches. The phenotypic output will be based on bacterial metabolic response(s) to antimicrobial(s). Since it can be uncertain whether the presence of an antibiotic-resistance-conferring genomic mutation will result in therapeutic failure, assessment of antimicrobial susceptibility/resistance must be performed using rapid methods that assess the bacterial response to antimicrobials;
• Be culture-independent: Directly detect targeted pathogens in vivo using novel imaging technologies, or in a clinical sample (swab, sputum, blood, serum, cerebrospinal fluid, urine, stool, etc.) obtained from individuals at multiple stages of infection.

In addition, the following diagnostic performance parameters are strongly encouraged:

• Rapid: Ideal diagnostic test time of approximately 3 hours for identification of species and determination of susceptibility profiles, which includes the time-required to process the clinical sample (e.g., incubation time, if appropriate) through detection and delivery of the final test result;
• Sensitive: Sensitivity should exceed current FDA-cleared standards for proposed targets from the same sample type;
• Specific: Specificity should exceed current FDA-cleared standards for proposed targets from the same sample type;
• Easy-to-use: Integrated, closed sample-to-answer system with automated data analyses or result presentation and with minimal operator training and expertise required;
• Cost-effective: Projected production and operating costs should be less than commonly used platforms for detecting infectious disease-causing pathogens;
• Capable of multiplexed differential detection of multiple pathogens, where appropriate.

The following characteristics are also desirable:

• Random Access: The proposed platform should allow imaging to be performed or samples to be run as needed.
• Adaptable: Capable of integrating new diagnostic assays/tests for targets as required, including detection of modified or new targets.

Note: Applications focused on development of environmental, agricultural, industrial and/or workplace surveillance/detection technologies are nonresponsive and will not be reviewed.

NOTE: Applications non - responsive to this FOA (as described above) will not be reviewed.

Each Center in the CETR program will be organized around a chosen theme focused on discovery, development and/or use of one or more countermeasures and/or technologies that target specified pathogens with the objective of translating research results to product development. Each Center will include the following components:

Each Center must include an Administrative Core, directed by the Program Director/Principal Investigator (PD/PI), under which all Center activities will be managed, coordinated, and supervised. The Administrative Core will include a Scientific Advisory Committee (SAC) that will participate in the development and management of the CETR and corresponding activities.

Each Center must include interdependent translational Research Projects focused on development and advancement of a new or improved medical countermeasure and/or associated platform/technology described above and targeting one or more select NIAID Emerging Infectious Diseases/Pathogens. Each Research Project must clearly and directly contribute to the Center theme and objective(s). The PD/PI will monitor all Research Projects and actively promote efforts that foster integration, collaboration and synergy across the projects. Research Project Leaders may be affiliated with either an academic organization or industry. For the purpose of this FOA, "industry" is defined as a large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, or chemical company, or a related non-profit entity.

Research Projects are expected to incorporate state-of-the-art technology and approaches and may include consortium arrangements for required activities. Applicants are encouraged to carefully consider the scope and range of research proposed and develop a Center that is coherent overall and consistent with available resources and personnel.

A Center may include development and maintenance of one or more scientific core resources and/or facilities that are essential for the activities of two or more Research Projects. Scientific Cores are intended to only serve the needs of Center project researchers and they may not conduct research independent of the served Research Projects.

Center themes and objectives may range from development of single or multiple countermeasures targeting a specific group of pathogens to development of modern technologies or platforms that target a wide array of pathogens/toxins, and translational activities may range from very early discovery-based efforts to late-stage preclinical development with industrial participation.

As an example, a Center focused on discovery and development of new therapeutics that target antimicrobial-resistant Gram-negative bacterial pathogens might have the following structure:

• Administrative Core
• Research Project 1: Bioinformatic/Proteomic Approaches to Identify Therapeutic Targets Common to Multiple Gram-negative Pathogens
• Research Project 2: Assay Development
• Research Project 3: High-throughput Screening for Small Molecule Therapeutics Against Multiple Gram-negative Pathogens
• Research Project 4: Development of Synthetic Peptide Antibacterials Against Multiple Gram-negative Pathogens
• Research Project 5: Preclinical Evaluation of Candidate Therapeutics

As a second example, a Center focused on discovery and development of a pan-filovirus immunotherapeutic cocktail:

• Administrative Core
• Research Project 1: Identification and Isolation of Protective Antibodies from Ebola and Marburg Survivors
• Research Project 2: Structure-Function Analyses of Protective Antibodies
• Research Project 3: Efficacy Testing of Candidate Antibodies
• Research Project 4: Optimization and Preclinical Evaluation of Candidate Immunotherapeutic Cocktails
• Animal Model Core (Efficacy and Preclinical Evaluation)

As a third example, a Center focused on structure-based development of a universal flu vaccine might have the following structure:

• Administrative Core
• Research Project 1: Computational Analysis of Immunogen Design/Function
• Research Project 2: Structure-Based Immunogen Design
• Research Project 3: Efficacy Testing and Down-selection of Protective Immunogens
• Research Project 4: Preclinical Evaluation of Candidate Vaccines

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

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

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

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

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH's ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Lianyong Gao, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5048
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	12 pages
Core (use for Scientific Cores)	6 pages each
Project (use for Research Projects)	12 pages each

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Projects: required, minimum three, maximum 6
• Scientific Cores: optional, each Core must support at least two Research Projects

When preparing your application in ASSIST, use Component Type 'Overall'.

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Center. Concisely describe the Center objectives.

Research Strategy: This narrative section summarizes the overall research plan for the multi-project application. 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.

Applicants should clearly define the Center theme, the significance of the Center theme regarding the countermeasure(s) targeted for development, the public health need and benefit of a successful effort, and the range of activities being pursued. Additionally, each application must detail how each Research Project contributes to the Center theme, objectives and project interdependence. Applications should outline expected synergies provided by the proposed center and summarize the special features in the environment and/or resources that make this application strong or unique.

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

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

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application in ASSIST, use Component Type 'Admin Core.'

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities & Other Resources: The PD/PI and Administrative Core staff are responsible for ensuring that all research activities are carried out in compliance with all federal and NIH regulations. A necessary component of a Center's success will be the availability of adequate access to BSL3/4 biocontainment facilities. Applicants must identify Research Projects that will require BSL3/4 containment facilities and provide a description of facilities that are available currently or planned at consortium institutions. A table listing each activity that requires BSL3/4 access and the likely facilities to be used should be included. The PD/PI and Administrative Core staff are also responsible for ensuring that appropriate systems are in place to provide for biosafety and security of materials, data, facilities and resources, including compliance with regard to Select Agent Regulations, Biosafety in Microbiology and Biomedical Laboratories (BMBL) Guidelines, Centers for Disease Control and Prevention and the National Institutes of Health, fifth Edition; U.S. Code of Federal Regulations 42 C.F.R. Part 73, 7 C.F.R. Part 331, and 9 C.F.R. Part 121.

• List all performance sites that apply to the specific component.
• Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The PD/PI must be the "Core Lead" of the Administrative Core.
• Include an administrative Core Associate that will be responsible for the daily administration and fiscal management of the Center.
• Include a key person expert in regulatory expertise capable to anticipate regulatory requirements and challenges pertinent to Emerging and Re-emerging Infectious Diseases.

Budget forms appropriate for the specific component will be included in the application package.

The Administrative Core budget may not exceed 5% of total direct costs requested. The Core Lead must commit at least 0.6 person months effort per year to these responsibilities. It is recommended that the Administrative Core Associate devote a level of effort ranging from 3 to 6 person months to the execution of the administrative details of the Center projects and to managing the day-to-day operations within the Center. Any additional Administrative Core personnel must be clearly justified. Regulatory expertise may be retained as defined effort or periodic consultation.

Each Center application budget must include funds for the PD/PI, Project Leaders, at least 3 external Scientific Advisory Committee members, additional Center Key Personnel (at the discretion of the PD/PI) to travel and attend annual mandatory reverse site visits in Years 1-4 of the project period.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core. In addition, state the core's relationship to the Program's goals and how it relates to the individual Research Projects or other cores in the application.

Research Strategy: The Administrative Core must include a Management Plan that identifies and discusses: The Administrative Core structure; the roles of Administrative Core personnel; the composition and duties of the Scientific Advisory Committee (see below); and the facilitation of communications throughout the Center and with NIAID staff. The plan should specifically address continual evaluation of research and development progress, communications, group meetings and teleconferences, presentation and publication of data, resource and model sharing, transmission of information and reagents, the identification and proposed resolution of problems and engagement of the NIAID staff as appropriate. A description of how consortia (subcontracts) will be managed should be provided and should include how communications such as periodic meetings and conference calls will be organized, managed and documented. The plan should also detail how CETR- and research-related travel will be managed.

Each Administrative Core must include the following:

Scientific Advisory Committee:

Each Center must establish a Scientific Advisory Committee (SAC) that includes the PD/PI and at least 5 non-conflicted external advisors. For Centers engaged in preclinical product development activities, at least 2 of the external advisors must have demonstrated and relevant industry-level expertise. Applicants MUST NOT name external SAC members in their applications. For applications under consideration for funding, SAC membership will be established in consultation with NIAID CETR program staff; applicants should only describe the expertise categories to be represented on the SAC and how the SAC will be utilized to guide Center activities.

Discuss the role of the SAC and the integration of its proposed expertise into the operations of the CETR. Applicants should describe procedures and approaches for obtaining SAC input via teleconferences, ad hoc and annual meetings, review of written materials/data, etc. If preclinical and/or product development activities are proposed in the application the SAC must include relevant experience.

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

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

Appendix:

Limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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

When preparing your application in ASSIST, use Component Type 'Projects'

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

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Core or Project Name)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Other Attachments:

Product Development Strategy

All Research Projects that include preclinical product activities must include a Product Development Strategy attachment. The Product Development Strategy attachment must be in pdf format with a filename of "Product_Development_Strategy.pdf" and include both a Milestones and Timelines section detailing project performance and timeline objectives and a Product Development Plan. This plan should include the participation of consultants with expertise in technology transfer and the development of regulated products. Only those projects for which the mechanism of action of the candidate product is reasonably well understood, possible routes of administration and formulations suitable for scalable production identified, and assays to assess product quality that are well developed should be considered for support beyond Technology Readiness Level (TRL) 5. In addition, animal models that are adequate to assess the ability of the product to induce a certain response and endpoints that will satisfy the Animal Rule should be identified and included for candidate products that may not be tested for efficacy in humans.

The overall Product Development Strategy, made up of the "Milestone and Timeline" and the "Product Development Plan sections," is limited to 12 pages total.

Milestones and Timeline: Applicants are required to provide detailed project performance and timeline objectives in a section entitled "Milestones and Timeline." This section must be no more than 5 pages and must include:

• A clear description of all interim objectives (research and/or developmental milestones) to be achieved during the course of the project. Applicants also must identify any impediments that could require a revision in the work plan or milestones with a discussion of alternative approaches.
• Detailed quantitative criteria by which milestone achievement will be assessed and factored into Go/No-Go decision-making.
• A detailed schedule or timeline for the anticipated attainment of each milestone and the overall goal(s).

Product Development Plan: Applicants are required to provide detailed development plans in a section entitled "Product Development Plan". This section must be no more than 7 pages and must include:

• A statement of the intended use/indication of the proposed product and public health gap the product is intended to fill.
• A statement of the value of the project, including lay description of key technology objectives, innovation, and advantages compared to competing products, technologies, or services.
• A clear description of the goal(s) of the project, including one (or more) intermediate products (tools), final product(s) or stage(s) of product development to be completed during the award period. A specific final product profile that is intended for licensing indication is not requested.

Additionally, the Product Development Plan must include descriptions pertaining to preclinical product development activities pertaining to the product proposed. Please see below for a list of points to be discussed as part of the Product Development Plan based on the type of product proposed.

Product Development Plans for therapeutic or vaccine projects should summarize:

• The performance specifications and features the product should have in order to provide therapeutic and/or immunological benefit.
• A description of the candidate product or lead series as it is currently configured.
• A description and developmental status of the assays for product release and characterization, including activity and efficacy.
• Data that support the characterization and selection of the candidate product for further development. Specifically, for vaccines, a summary of data that demonstrates efficacy in in vitro assays and/or in vivo models for one or more of the selected agent(s). This includes: a detailed description of the assays and animal models, the choice of pathogen challenge, strain and route, and a rationale for the choice of animal model, pathogen challenge, strain and route, as well as for the outcome/endpoints selected; documentation that the animal infection experiments were performed under well-controlled experimental conditions.
• Discussions with FDA, if any, which are relevant to development activities for the candidate product/technology.

Product Development Plans for diagnostics projects should summarize:

• The performance specifications the product (diagnostic assay, method, technology, etc.) should have to demonstrate it is equivalent or superior to the gold standard for identifying the proposed agent(s), including clinical sensitivity in appropriate human samples, clinical specificity in appropriate human samples, analytical sensitivity (limit of detection), analytical reactivity (pathogen strains detected for each pathogen), analytical specificity (cross-reactivity), and analytical reproducibility (test replicates at different agent concentrations, at different sites, etc.). If no FDA-cleared test is available for the agent(s), the specifications should be equivalent to or exceed performance specifications of FDA-cleared tests for similar types of agent(s).
• Data that support the selection of the candidate product for further development, including an assessment of the present capacity of the diagnostic method, technology or assay to meet the performance specifications.
• Discussions with FDA, if any, which are relevant to development activities for the candidate product.

When appropriate, and as part of the Product Development Plan, applicants should document compliance with guidelines that govern GLP, as defined by 21 CRF (58), and CGMP, as defined by 21 CRF (211), manufacturing and/or IND/IDE enabling studies that will be performed under the project award as they would be applicable to eventual product licensure in the U.S. Applications for projects involving CGMP manufacture should ensure inclusion of appropriate personnel to provide regulatory guidance before, during and after manufacture.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

Each project leader must commit at least 1.2 person months effort to their project per year.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Specific Aims: List, in priority order, the broad long-range objectives and goals of the proposed project. Concisely describe the translational activities to be performed. In addition, state the individual research project's relationship to the Program's goals and how it relates to other projects or cores.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the Center'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.

For each Research Project describe the research design conceptual procedures, and analyses to be used to accomplish the specific aims of the project. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims. As part of this section, provide a tentative sequence or timetable for the project. Describe how the research strategy is informed by an understanding of the regulatory process. Describe anticipated regulatory barriers and propose research and/or strategies to overcome these barriers.

Early stage translational Research Projects (i.e. Research Projects that will not include preclinical activities that necessitate an associate Product Development Strategy attachment as described above) must include detailed project performance and timeline objectives. Additionally, projects must identify and address anticipated regulatory barriers and propose research and/or strategies to overcome these barriers (see below). This is particularly important for new classes of medical countermeasures for which there are no precedents for FDA approval.

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

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

Whenever possible, the awardee is expected to provide software certified by the Open Source Initiative, to guarantee the right of others to read, redistribute, modify, and freely use the software, consistent with achieving the goals of the program.

Program-generated novel reagents (e.g., expression vectors, mutant strains, libraries, protein clones), should be made available through NIAID-supported repositories, such as the NIAID BEI Resources or in other repositories as identified by the SAC in consultation with the NIAID.

Program-generated data and software include, for example:

• all research data (both experimentally and computationally generated) and associated metadata;
• database schema and specifications;
• experimental protocols and Standard Operating Procedures (SOPs); and
• data analysis tools, models and algorithms generated under this contract, including model parameters and source code, complete use documentation and tutorials.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Projects)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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

When preparing your application in ASSIST, use Component Type 'Core.'

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

SF424 (R&R) Cover (Scientific Cores)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Scientific Cores)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Cores)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Scientific Cores)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Scientific Cores)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Scientific Cores)

Budget forms appropriate for the specific component will be included in the application package.

The Core Leader should commit to the Core at least 1.2 person months of effort.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Scientific Cores)

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core. In addition, state the core's relationship to the Program's goals and how it relates to the individual Research Projects or other cores in the application.

Research Strategy: Describe and justify the role of the Core in the overall Center research activities, describe how the proposed core activities will contribute to meeting the Center's goals and objectives, specify how a proposed scientific core provides a unique service that cannot be obtained through institutional or commercial means, and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the application. Provide details of the services or resources provided by the optional cores to at least two Research Projects and clarify how the optional cores are not duplicative of other services or facilities. Additionally, plans for staffing, managing, and prioritizing use of the cores must be provided, as well as plans for determining fees to users if charging fees is necessary.

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

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

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Scientific Cores)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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

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

• Does the application have a single clearly defined and scientifically justified theme?
• Does the application adequately explain:
• The scientific merit of each Research Project and Core?
• The program as a whole? The significance of the overall program goals?
• The scientific gains and synergy achieved by combining the component projects into a multi-project program beyond the gains achievable if each project were pursued independently?
• Are the overall program goals significant and focused on studies that increase knowledge needed to advance the translational activities of the center?
• How well does the overall program incorporate innovative concepts and approaches?
• Is the program as a whole cohesive and do the Research Projects and Cores relate to a single common theme demonstrating cohesion, multidisciplinary interactions, coordination, and synergy?

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the Project Leaders, 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?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Does the approach take into consideration the anticipated regulatory process and any anticipated regulatory barriers?

Environment

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

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

Is the administrative and organizational structure appropriate and adequate to achieve the goals of the proposed program? Is the Management Plan for fiscal accountability and communication within the program appropriate? Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate? Are plans for communication among the Centers adequate to facilitate collaborative activities? Do the PD/PI and Key Personnel commit sufficient time and effort to adequately manage the Program? Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Is the Core sufficiently justified? Does it support at least two Research Projects? Is the core adequately connected to the central focus of the overall program? Are the facilities or services provided by the core (including procedures, techniques, and quality control) high quality? Will the services be used effectively? Are the core leader and key personnel well qualified and is there an adequate commitment of time?

As applicable for the project or core proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Product Development Strategy

For Research Projects engaged in preclinical product development activities;

• Are the Milestones appropriate and feasible?
• Does the Product Development Plan adequately address the specific areas described in the FOA?
• Is the proposed Product Development Plan feasible and appropriate for proposed and future product development?
• Is the Product Development Plan consistent with achieving the goals of this program?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project or core involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

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

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

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

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

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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

As part of the scientific peer review, all applications:

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

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

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

The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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.

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 Part 75, 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 for:

PD(s)/PI(s), will have the primary responsibility for coordinating the Projects and Cores within the overall Program. Specifically, the PD(s)/PI(s) have primary responsibility as described below.

The PD(s)/PI(s) will be responsible for defining the research objectives, approaches and details of the projects within the guidelines of the FOA and retains primary responsibility for the planning, directing, and executing the proposed scientific activities.

In addition, the PD(s)/PI(s) will be responsible for:

• Organizing and chairing annual site visit activities. The reverse site visits are anticipated to be held at a location at/near Rockville, MD or at another NIAID-approved site and will last 0.5 to 1 day
• Making sure that the NIAID Data Sharing Plan are properly implemented by the personnel of the Research Projects and Cores
• Advertising the availability of the Program generated resources through outreach activities.
• Provide solicited progress reports in a format to be defined by the NIAID after award.

Scientific Advisory Committee (SAC):

The SAC will participate in the development and management of the CETR and corresponding activities. The SAC will attend the CETR annual meeting to review Center activities and evaluate progress, adherence to milestones and timelines, and the continued relevance of each Research Project to the overall objective(s). The SAC will facilitate go/no go decision making, recommend new directions as appropriate and provide upon request of the PD/PI and NIAID Project Scientist a comprehensive written evaluation of the group's activities and the panel's recommendations following the annual meeting. Additionally, the SAC will be responsible for guiding and reviewing CETR program-sponsored Supplemental Research Project applications.

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.

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

The role of the NIAID/NIH Project Scientist is to support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PDs/PIs. The NIAID Project Scientist will work closely with the PD(s)/PI(s) and other Program member scientists to facilitate collaborations and to leverage the resources available to the Program.

The NIAID Project Scientist will monitor the progress of the Program, help coordinate research approaches among all Programs funded through the FOA, and contribute to the shaping of research projects or approaches as warranted. The NIAID Project Scientist will support and facilitate this process but will not direct it.

The NIAID Project Scientist will keep the Program informed about other ongoing studies supported by NIAID to avoid duplication of effort and encourage sharing/collaboration in infectious diseases research. The NIAID Project Scientist will coordinate access for the Program to other NIAID resources, as well as assist the research efforts of the Program by facilitating access to fiscal and intellectual resources provided by industry, private foundations, NIH intramural scientists and other federal government agencies as appropriate.

The NIAID Project Scientist will retain the option to recommend withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award.

Additionally, a NIAID program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program official may also serve as the NIAID Project Scientist.

Areas of Joint Responsibility include:

The NIAID Project Scientist and the PD/PI will hold regular program-wide discussions to facilitate the achievement of program goals. In the event that some members of the Programs develop common research interests, working groups may be formed to pursue collaborative activities.

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.

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

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

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

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.

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

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

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Michael R. Schaefer, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3364
Email: [email protected]

Lianyong Gao, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5048
Email: [email protected]

Mable Nee
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7593
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.