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

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

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

The National Institute of Allergy and Infectious Diseases (NIAID) supports extramural research focused on understanding, controlling and preventing diseases caused by virtually all infectious agents. In response to the threat presented by increasing numbers of infections by multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (Mtb), the NIAID Division of Microbiology and Infectious Diseases (DMID) has established research programs to facilitate development of vaccines, therapeutics and diagnostics targeting mycobacterial diseases. The purpose of this Funding Opportunity Announcement (FOA) is to solicit research applications for milestone-driven projects focused on establishing proof-of-concept for and/or preclinical development of candidate vaccines targeting infection with Mycobacterium tuberculosis (Mtb) and/or tuberculosis disease (TB).

Tuberculosis has superseded AIDS as the leading cause of death by infectious diseases worldwide. The World Health Organization (WHO) estimated that in 2014, 9.6 million persons fell ill with TB and 1.5 million succumbed to the disease, including 140,000 children. In contrast to efforts that have reduced the incidence and prevalence of HIV/AIDS, the combined impact of increasing resistance to current antibiotics and limited pace of development of new therapeutics against Mtb has led to increased global morbidity, mortality and rising healthcare costs associated with TB. The currently used TB vaccine, Bacille Calmette-Gu rin (BCG), provides some protection against severe forms of pediatric TB but exhibits limited effectiveness to protect against adult pulmonary TB. Accordingly, there is a critical need for new and effective interventions to reduce the global burden of TB in the next decade.

Current TB control protocols emphasize diagnosis and treatment of persons that have developed active pulmonary TB. However, this approach is limited in reducing spread of the disease as airborne transmission of Mtb is possible until a patient responds to therapy. Moreover, transmissible Mtb can persist for years in latently-infected individuals and without treatment, these individuals can develop active pulmonary TB and are capable of spreading Mtb to others. Development of effective vaccines that prevent Mtb infection and/or the transition from infection to active TB would protect the public from infection, improve clinical options for infected patients, and help prevent spread of the disease.

TB is a complex disease that most commonly affects the lungs and characteristically leads to development of granulomas, which are compact organized aggregates of Mtb and immune cells. The unique cellular structure of granulomas allow Mtb to persist and compromises treatment with antibiotics. The complexity of TB, coupled with the inability of Mtb infection to engender natural immunity, presents unique challenges to identification of candidate vaccines. In alignment with the vaccine research and development priorities outlined in the White House National Action Plan for Combating MDR-TB (https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf), this FOA seeks to stimulate efforts to address these challenges and enable development of efficacious vaccines against Mtb.

The objective of this FOA is to support milestone-driven research projects focused on establishing proof-of-concept for and/or preclinical development of candidate vaccines against Mtb infection and/or TB. This initiative seeks to facilitate identification of promising lead vaccine candidates and support preclinical development of established leads. For the purpose of this FOA, candidate vaccine is defined as a vaccine or related vaccine product (e.g. prime/boost vaccine, therapeutic vaccine, vaccine/adjuvant combinations, etc.); lead candidate is defined as a candidate vaccine for which proof-of-concept data have been obtained, and preclinical development is defined as all activities beyond lead candidate identification.

Proof-of-Concept Activities

This FOA will support translational activities to establish proof-of-concept for promising candidate vaccines. Projects must initiate with favorable candidates with demonstrated capacity to elicit an immune response in a relevant animal model for Mtb infection and/or TB. Approaches to demonstrate proof-of-concept and evaluate candidate vaccines under a variety of informative experimental conditions (e.g. inclusion of clinical Mtb isolates as challenge strains, use of recently developed novel small animal models, models that incorporate pre-exposure to mycobacterial species, etc.) are encouraged. Relevant aspects of immune response should be investigated in the most appropriate models to gain further insight into biological complexity underlying vaccine induced immunity.

Proof-of-concept studies may include, but are not limited to:

• Evaluation of vaccine candidates in functional in vitro assays;
• Assessment of immunogenicity in relevant animal models of Mtb infection and/or TB;
• Determination of efficacy in relevant animal models;
• Assess impact of challenge strain or mycobacterial pre-exposure efficacy;
• Iterative optimization of candidate vaccines or vaccine/adjuvant combinations;
• Head-to-head comparison of candidate vaccines;
• Advancement of promising prime-boost vaccine combinations with efficacy exceeding that of Bacille Calmette-Guerin (BCG) vaccine.

The completion of proof-of-concept activities is expected to result in the selection of a lead candidate vaccine or related product deemed appropriate for subsequent preclinical product development.

Preclinical Development Activities

This FOA will support preclinical development of a lead candidate vaccine against Mtb infection and/or TB for which proof-of-concept data have been obtained in a relevant animal model. Proposed activities should focus on advancement of the lead candidate vaccine toward licensure. Applications that would significantly advance a candidate vaccine toward clinical usefulness are responsive and highly encouraged; however, projects are not required to result in a "final" product, nor is it necessary to propose completion of the product development process up to the point of readiness for clinical trials or validation within the time frame of the project.

Preclinical development activities may include preclinical evaluation, and if warranted, scale-up production under GMP to provide sufficient quantities for preclinical FDA-required animal studies. Standard IND-enabling activities such as cGMP manufacturing, stability studies, lot release assays, and execution of GLP repeated dose toxicology studies are encouraged for more advanced candidate vaccines. Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) are strongly encouraged to obtain expertise in the areas of product development planning and target product profile development in general, and regulatory matters in particular. Expertise needed to fulfill project objectives may be retained as defined effort or may be included as periodic consultation on specific issues.

For preclinical development projects, approaches should consider the ultimate potential of a candidate vaccine to elicit safe and protective responses in a diverse human population. Preclinical projects may include, but are not limited to, one or more of the following product development activities:

• Optimization of lead vaccine candidate;
• Evaluation of safety, toxicity and immunogenicity in animals;
• Evaluation of efficacy in appropriate animal challenge models;
• Optimization of dose and route of delivery in preclinical evaluation;
• Optimization of production methodology including process development;
• Scale up and production of candidate vaccines including cGMP production;
• Process development for the production of vaccine components, including Quality Assurance (QA)/Quality Control (QC), methods for product recovery, characterization, purification, identity, stability, etc.;
• Manufacture under GLP or cGMP to provide quantities sufficient for preclinical and early clinical evaluation;
• Performance of preclinical testing for safety, toxicity, and efficacy in animal models and other benchmarks required for successful submission and review of an Investigational New Drug (IND) application by the Food and Drug Administration (FDA);
• Optimization of delivery platforms, antigen and adjuvant combinations/formulations; and
• Advanced development of formulation methodologies that obviate the need for cold-storage of the resulting product and/or extend shelf-life.

Industrial Participation

All applications submitted to this FOA must demonstrate substantive investment by at least one industry participant. 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 with an established track record in product development. Substantive investment" is defined as a significant commitment of one or more resources to the project including, but not limited to: research and development plan support/guidance, product development support/guidance, personnel, in kind contributions of materials and/or reagents (i.e. adjuvant, innovative biotechnology platforms, scale up of GMP manufacturing, etc.), provision of animal or other laboratory models for evaluation, subcontracts, data management resources, regulatory support, or alterations/renovations of facilities or provision of equipment to address biohazard concerns. The PD(s)/PI(s) of the project may be affiliated with either industry or an academic organization; however, if the PD(s)/PI(s) is/are from academia, an industrial partner must be identified in the application. There is no requirement for an academic participant on applications submitted by industrial organizations.

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

• Projects focused on identification of new vaccine candidate(s).
• Projects focused on de-novo antigen discovery.
• Projects focused on development of new adjuvants.
• Projects lacking appropriate preliminary/immunogenicity data supporting the target candidate vaccine(s).
• Proof-of-concept projects that lack a Milestones and Timelines attachment.
• Preclinical development projects that lack the Product Development Strategy attachment.
• Projects from academic institutes that lack substantive investment by at least one industry participant.
• Clinical trials (all phases).

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

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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.
• 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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:

Amir E. Zeituni, Ph.D.
Telephone: 301-761-6872
Fax: 301-480-2408
Email: amir.zeituni@nih.gov

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

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

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

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

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

Other Attachments: Applications must include one of the two following options: 1) Proof-of-Concept Studies or 2) Preclinical Product Development Activities. These attachments are separate from and in addition to the Research Plan and must not be used to circumvent the page limits of any other section of the application.

1) Proof-of-Concept Studies

Applications proposing only proof-of-concept activities during the project period are required to include a Milestones and Timeline attachment as a pdf document with the filename of Milestones_and_Timeline.pdf. Applications lacking the required Milestones and Timeline section will be deemed incomplete and will not be reviewed. The Milestones and Timeline 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.
• A detailed schedule or timeline for the anticipated attainment of each milestone and the overall goal(s).

2) Preclinical Product Development Activities

Applications proposing proof-of-concept studies and subsequent preclinical development activities for a selected lead candidate vaccine, or only preclinical development of a previously identified lead candidate vaccine, must include a Product Development Strategy that includes both a Milestones and Timeline and a Product Development Plan section. The Product Development Strategy attachment must be in pdf format with a filename of Product_Development_Strategy.pdf. Applications lacking a required section of the Product Development Strategy section will be deemed incomplete and will not be reviewed.

The overall Product Development Strategy, made up of the "Milestone and Timeline" and the "Product Development Plan sections," is limited to 12 pages. (Note: Applicants must not add additional attachments to circumvent page limits.)

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.
• 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 development of the candidate vaccine. For the purpose of this FOA, preclinical is defined as all activities beyond lead candidate identification.

Product Development Plans for vaccine projects should summarize:

• The performance specifications and features the vaccine or related product should have in order to provide immunological and/or therapeutic benefit.
• A description of the candidate vaccine or related product 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 vaccine for further development. Specifically for vaccines, a summary of data that demonstrates efficacy in in vitro assays and/or in vivo models for the targeted agent. 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.

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

Detail the demonstrated expertise, experience and accomplishments of key team members to demonstrate appropriate areas of product development planning and target product profile development in general, and regulatory matters in particular. Expertise needed to fulfill project objectives may be retained as defined effort or may be included as periodic consultation on specific issues.

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

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

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

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

Research Strategy: Applications must address the following:

• Describe how the project will significantly advance the development of a candidate vaccine against Mtb infection and/or tuberculosis disease (TB).
• For preclinical product development, provide and describe pre-established proof-of-concept data in support of the single candidate vaccine or related product to be developed, and plans to progress the candidate through preclinical development.

Industry Participation: For applications from academic institutions, identify the industrial partner(s) and describe the organization's participation and investment in the project.

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

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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 our Post Submission Application Materials 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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is this project likely to significantly advance the development of a candidate vaccine against Mtb infection and/or tuberculosis disease (TB)? If the aims of the application are achieved, is an important biomedical countermeasure or product likely to result? 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? For preclinical product development applications from academic institutions, does the research plan leverage appropriate industry involvement to accelerate candidate vaccine development, some aspects of which may not be inherently innovative?

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?

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

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

Proof of Concept Studies

For applicable applications, are the Milestones and Timelines proposed to achieve the goals of the project appropriate and feasible?

Product Development Strategy

For applicable applications, is the Product Development Strategy well-conceived and appropriate for the proposed countermeasure category? Are the Milestones and Timelines proposed to achieve the goals of the project appropriate and feasible? Is the proposed Product Development Plan feasible and appropriate for proposed and future product development?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

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

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

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

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

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

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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (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: mschaefer@niaid.nih.gov

Amir E. Zeituni, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6872
Email: amir.zeituni@nih.gov

Cynthia Rodriguez
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5391
Email: cynthia.rodriguez@nih.gov

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

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