Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Live-attenuated vaccines, and some vaccines based on inactivated or killed agents, include natural/endogenous adjuvants that stimulate both the innate and adaptive arms of the immune system. Subunit vaccines contain specific molecular entities and generally lack immune stimulators found in whole organism-based vaccines, creating a need for exogenous adjuvants to induce protective immunity. The aluminum-based adjuvant, Alum, was the only adjuvant in vaccines licensed for use in the U.S. until 2009, when the U.S. Food and Drug Administration (FDA) approved Cervarix, an HPV vaccine containing the adjuvant AS04. This adjuvant, developed by Glaxo Smith Kline (GSK), is a combination of alum and 3-O-desacyl-4'-monophosphoryl lipid A (MPL-A), an immune-stimulating lipid.

In 2013, the FDA approved a pandemic H5N1 influenza vaccine that includes AS03, an oil-in-water emulsion combination adjuvant developed by GSK. This vaccine is part of the U.S. vaccine stockpile and is not commercially available. In 2015, the FDA approved the MF59-adjuvanted FLUAD influenza vaccine for use in people 65 years of age and older. MF59 is a squalene-based oil-in water emulsion adjuvant that has been used for years in pediatric and adult influenza vaccines licensed in more than 30 countries. Most recently, in 2017, the FDA approved two new adjuvanted vaccines: the GSK AS01-adjuvanted shingles (herpes zoster) vaccine, Shingrix, for use in adults 50 years of age and older; and the Dynavax CpG-oligodeoxynucleotide (ODN) adjuvanted hepatitis B vaccine, Heplisav-B, for use in people 18 years of age and older. AS01 is a liposome-based combination adjuvant containing MPL and the saponin QS-21; and CpG-ODN is a short single-stranded DNA molecule that mimics unmethylated bacterial DNA and triggers innate immune responses through activation of Toll-like receptor 9 (TLR9).

While these recent approvals bring the number of non-alum adjuvanted FDA-approved vaccines to six (with two containing combination adjuvants), additional adjuvants are needed to improve vaccine efficacy in neonates, young children, pregnant women, the immune compromised and the elderly. In addition, the currently used adjuvants may not induce the types of immune responses required to protect against infectious agents for which vaccines currently do not exist. Recent technologic and scientific advances have increased our understanding of the pathways regulating innate and adaptive immune responses, offering opportunities to develop novel or modify existing adjuvants to safely trigger long-term protective immunity.

Live-attenuated vaccines contain a wide variety of immune agonists and can provide durable protection, sometimes following a single immunization. For example, a single dose of the attenuated yellow fever vaccine YF-17D is known to produce a high-quality immune response (> 98% protection), which lasts up to 35 years. It has been demonstrated that the YF-17D vaccine stimulates innate signaling pathways for Toll like receptors (TLRs) 2, 7, 8 and 9 in dendritic cells, which in turn activate multiple innate and adaptive immune components. The activation of numerous components of the immune system offers a compelling explanation for the strong and durable protection against infection that is induced by this vaccine. The combination of adjuvants represents a method to recapitulate such beneficial immune stimulation in a controlled and defined way. Exogenous adjuvants can enhance vaccine efficacy, promote antigen dose sparing, and may contribute to more rapid and durable immune protection against pathogens. An understanding of the molecular mechanisms that are responsible for the activity of combination adjuvants would give rise to the development of novel adjuvant combinations that target multiple immune pathways. Optimal adjuvant combinations would trigger induction of antigen-specific protective and long-lasting immunity, including enhanced antibody magnitude and breadth, and aid design of a safe and effective vaccines.

The development of effective adjuvants is a high-priority research area for NIAID. In April 2018, NIAID convened a Blue-Ribbon panel to review and further refine the Institute’s research agenda for the discovery, development, and clinical evaluation of vaccine adjuvants. With the panel’s input, NIAID developed the Strategic Plan for Research on Vaccine Adjuvants. It was noted that many adjuvant research projects are based on individual adjuvants. In addition, current findings of vaccine potentiation by adjuvant combinations support the need for mechanistic research in this area. Although some new combinations such as AS01 (liposome-based combination adjuvant containing MPL and the saponin QS-21) and AS04 (alum + MPL-A) are already used in licensed vaccines, the molecular underpinnings of their adjuvant effects are not fully understood.

NIAID initiated the Molecular Mechanisms of Combination Adjuvants (MMCA) program in 2016 to promote the investigation of new adjuvant combinations, and to understand the mechanisms by which combination adjuvants improve vaccines. Awards were made to seven investigators to study a variety of different adjuvant combinations. These investigators identified combinations that targeted multiple innate immune pathways or that enhanced B and T cell mediated immunity, examined the mechanisms associated with differences in responses to live attenuated vs. adjuvanted vaccines and characterized induction of tissue-specific immunity.

Research Objectives

This program will support research to define the molecular and immunological mechanisms triggered by adjuvant combinations leading to long-term protective immunity against infectious diseases. One or more adjuvant combination(s) may be proposed for examination.

Studies should focus on exploration of the mechanism(s) of action of combination adjuvants that have already been shown individually to be effective in enhancing or modulating immune responses when compared with antigen alone (i.e., model antigens, pathogen-derived molecules or vaccine components). A strong rationale for combining adjuvants based on what is known about their individual mechanism(s) of action is required. Adjuvant combinations that include non-TLR agonists are of particular interest. Examination of immune mechanisms in animal models is required. These mechanisms may include but are not limited to stimulation of multiple immune receptors, or activation of multiple signaling pathways in animal models or in in vitro systems. Use of in vitro systems is allowed and inclusion of human cells (primary and/or cell lines) is encouraged, but not required.

Mechanism of Action (MOA) studies may include, but are not limited to:

• Antibody production and avidity, qualitative measures of B cell and antibody function
• CD4 and CD8 T cell activation and function
• Induction and maintenance of innate and adaptive immune memory
• Tissue-specific immunity
• Studies of signaling pathways and cascades
• Characterization of innate immunity including, but not limited to: studies of dendritic cells, macrophages, NK cells, innate lymphoid cells, neutrophils, and complement
• Pathogen challenge studies showing sterile protection or mitigation of disease
• Systems immunology analyses
• Safety studies: measurement of serum levels of proinflammatory cytokines or determination of weight loss, fever, or tissue damage to demonstrate improved immunogenicity without increased reactogenicity.
• Determination of correlates of immunity
• Use of computational/mathematical modeling to examine MOA and synergistic effects (must include experimental validation)

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

• Studies on AIDS, HIV, or SIV.
• Projects that do not examine immune mechanisms in animal models.
• Projects that use only one adjuvant without combining it with at least one additional adjuvant.
• Clinical trials. However, the use of samples obtained from human subjects in clinical trials funded through other mechanisms is allowed, as is the use of samples obtained from human subjects treated with licensed vaccines or drugs for the FDA approved indication.
• Projects focused primarily on screening assays to identify adjuvants or adjuvant combinations, rather than on mechanism of action.
• Projects that focus primarily on technology, reagent, or animal model development. However, these may be included as necessary parts of the project if well justified by the research aims and preliminary data.
• The use of compounds that have not previously been shown to have adjuvant activity when used individually or when used in combination.
• Studies that are focused on the development of vaccines, or on determining vaccine immunogenicity/efficacy, rather than focusing on the mechanisms of action of combination adjuvants.

Milestones

This program is milestone-based and includes the flexibility to quickly revise milestones and/or aims within the scope of the original peer-reviewed application.

Milestones will be negotiated after award, and NIAID may reduce the amount of the award for projects that do not achieve negotiated milestones in future years.

Annual Meeting and Site Visits

A kickoff meeting and annual meetings will be organized by NIAID in order to share both positive and negative results, and materials, including reagents and techniques, among all awarded investigators; evaluate individual program progress; and foster collaborations among all the funded investigators. These meetings will convene yearly in the Rockville, Maryland area. The PD/PI from each award is required to attend the kickoff meeting and annual meetings.

Annual site visits from NIAID program staff: at the NIAID PO's request, the PD/PI will plan the meeting time and agenda in coordination with NIAID program staff and arrange for key project personnel to be available to give presentations and interact with NIAID staff at the meeting.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

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

• 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) 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 to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.

2. Content and Form of Application Submission

Letter of Intent

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:

Maggie Morris Fears, Ph.D.
Telephone: 301-761-5444
Email: maggie.morrisfears@nih.gov

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

The budget must include the following:

• Funds to accommodate travel by the PD(s)/PI(s) plus up to two staff members to attend an initial 1-day kick-off meeting and subsequent 2-day annual meetings to review progress, which will be held in the Rockville, Maryland area.

The following budget item is allowed:

• Travel for PD/PI and up to 2 staff members to attend one scientific meeting per year.

Research Strategy: Applications must include the following:

• A logical rationale for selection of specific adjuvant combinations, based on what is known about their individual mechanism(s) of action
• A rationale for choice of model antigen system and route(s) of immunization for testing adjuvanticity of the combination adjuvant(s)
• A strong rationale for not including at least one non-TLR ligand adjuvant, if applicable
• Qualitative as well as quantitative measures of immune activation/effectiveness. Examples include, but are not limited to: measures of avidity of TCRs and antibodies, breadth of immune responses, epitope specificity, duration of protective immunity, and/or identification of correlates of adjuvanticity
• A timeline with project milestones

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. To promote public access to the data generated through the program, all Program Directors (PDs)/Principal Investigators (PIs) funded under this initiative will be expected to share their data through an open access data sharing repository such as ImmPort (http://www.immport.org) or other data resources designated by NIAID, NIH.
• Each applicant should outline reagents, resources, or expertise that they can share with other investigators funded through the program.

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Significance

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

Investigator(s)

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

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 included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA

• Is the application appropriately focused on determining adjuvant mechanism of action?
• Are the proposed qualitative and quantitative measures of immune activation/effectiveness and adjuvanticity appropriate?
• Is there a strong rationale for the chosen combination of adjuvants, as well as the model antigen system proposed for testing adjuvanticity?
• Are the timeline and milestones reasonable and appropriate for the work proposed?

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?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories 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 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is 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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Applications from Foreign Organizations

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.

Select Agent Research

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).

Resource Sharing Plans

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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases, 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.

• 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.

Applications will be assigned on the basis of established PHS referral guidelines 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.

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) 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:

• Apprising the NIH of any potential impediments to execution of the goals of their MMCA project.
• Ensuring successful completion of the data- and other resource-sharing plans as appropriate.
• Distributing animal models and other reagents produced by this award to the research community in a timely manner, through appropriate existing repositories (e.g. the Mutant Mouse Regional Resource Centers, BEI Resources, commercial sources, etc.).
• 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 DHHS, 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 NIAID Project Scientist will support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibility that remains with the PD(s)/PI(s).
• The NIAID Project Scientist may negotiate a reduction of support from any cooperative agreement that does not achieve its goals according to the milestones agreed to at the time of the award.
• NIAID staff may use information obtained for the preparation of internal reports on the activities of the study.
• Additionally, a program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Final annual milestones based on those proposed in the application will be negotiated with the NIAID Program Officer at the time of award to ensure that they clearly state the interim project objectives and provide explicit, detailed, and quantitative measures for assessing project progress and success. Subsequent annual funding will depend on progress in meeting these milestones.

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.

3. Reporting

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 agreementsare 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.

Section VII. Agency Contacts

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Cheryl Lapham, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-498-1366
Email: clapham@niaid.nih.gov

Maggie Morris Fears, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444
Email: maggie.morrisfears@nih.gov

Elizabeth Sihombing
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5530
Email: elizabeth.sihombing@mail.nih.gov

Section VIII. Other Information