Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title

Molecular Mechanisms of Combination Adjuvants (MMCA) (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

Funding Opportunity Announcement (FOA) Number

RFA-AI-15-005

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.855; 93.856

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits applications that propose studies of the mechanism of action of a combination of two or more vaccine adjuvants (combination adjuvant). Adjuvants that are used in these studies must already have shown immune boosting activity when used individually in licensed or unlicensed vaccines (e.g. experimental or candidate vaccines).   

The purpose of this FOA is to build upon the investment the NIAID has already made into adjuvant research, by combining previously identified and characterized adjuvants and characterizing their immune stimulating activity. The Cooperative Agreement grant mechanism allows for coordination of these research efforts with NIAID’s overall adjuvant research objectives. The long-term goal is to promote the development of novel adjuvant combinations which will improve the immunogenicity of vaccines while addressing concerns related to reactogenicity.

Key Dates
Posted Date

February 10, 2015

Open Date (Earliest Submission Date)

June 9, 2015

Letter of Intent Due Date(s)

June 9, 2015

Application Due Date(s)

July 9, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

November 2015

Advisory Council Review

January 2016

Earliest Start Date

March 2016

Expiration Date

July 10, 2015

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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.

Table of Contents

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

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Currently, only a limited number of adjuvants are used as vaccine components in the United States. Many current vaccines, or those in development, induce a suboptimal immune response and require large antigen doses, multiple immunizations, or periodic boosting to provide long-term protection. The use of adjuvants in vaccines can enhance vaccine efficacy, promote dose sparing, and may contribute to more rapid and durable immune protection against pathogens.  The development of effective adjuvants is a high-priority research area for NIAID, which has invested significantly in the discovery and development of new adjuvants since 2003.  The contract Adjuvant Discovery Program supports early stage discovery and initial characterization of novel adjuvant candidates, and the contract Adjuvant Development Program seeks to advance further testing and formulation of promising vaccine adjuvants for licensure and use in humans. Together, these programs have led to 2 phase I clinical trials, 18 patents, and over 100 scientific publications.  However, the vast majority of these studies are based on individual adjuvants, and the possibility that combinations of adjuvants may increase both efficacy and safety requires systematic investigation. NIAID, as part of its ongoing commitment to promote discovery and innovation in adjuvant development, is initiating the Molecular Mechanisms of Combination Adjuvants (MMCA) program to promote investigation of new adjuvant combinations, and to understand the mechanisms by which combination adjuvants induce their effects.

In November 2010, 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. Two of the goals of this plan were: 1) understanding how new and existing adjuvants and combinations of adjuvants help enhance the protection conferred by vaccines and 2) understanding the immunological functions that influence the activities of different types of adjuvants. An understanding of immunological functions and the molecular mechanisms that are responsible for the activity of combination adjuvants could lead to future development of adjuvant combinations that target multiple immune pathways.  These pathways, likely affecting multiple immune cell types within both innate and/or adaptive immunity, could improve the duration of the immune response, as well as the quality and magnitude of the response.  

There is already some evidence that the simultaneous stimulation of various immune targets by combination adjuvants could produce a more effective and longer lasting immune response. Some highly effective vaccines stimulate multiple immune pathways. For example, the attenuated yellow fever vaccine YF-17D is known to produce a high quality immune response (> 98% protection), which lasts for at least 10 years, and up to 35 years, after a single vaccination. 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 arms of the immune response offers a compelling explanation for the strong and durable protection against infection that is induced by this vaccine. Combination adjuvants represent an attempt to recapitulate this beneficial immune stimulation in a controlled and defined way. 

Current findings of vaccine potentiation by adjuvant combinations support the need for mechanistic research in this area.  For example, the combination adjuvant AS04 consists of alum, which is thought to facilitate antigen uptake by dendritic cells, immune cell recruitment to the injection site, and activation of the NLRP3 inflammasome, in combination with monophosphoryl lipid A, which is a TLR-4 receptor agonist.  AS04 has been shown to increase cell-mediated and humoral immune responses, when compared to vaccines adjuvanted with alum alone.  The mechanisms by which these combination adjuvants work have not yet been fully elucidated.

The primary objective of the MMCA program is to support further exploration of the potential of adjuvant combination and to support studies that define the molecular and immunological mechanisms by which these combinations work.  As an understanding of the innate immune system has increased, significant progress has been made in finding novel adjuvant candidates and describing the cellular and molecular mechanisms of adjuvanticity. Although a single adjuvant can enhance immune responses and the efficacy of a vaccine, it is not always sufficient for long-term protection, particularly in vulnerable populations.  Adjuvant combinations that target multiple receptors and pathways hold great potential to improve protective vaccine responses.

Research Objectives

This program will support research to determine optimal combinations of adjuvants capable of triggering long-term protective immune responses to prevent or ameliorate infectious disease.

These studies are expected to provide novel insights into the mechanisms of combination adjuvant activity.  One or more adjuvant combination(s) may be proposed for examination. 

Although it is not required, research objectives may include optimization of the formulation of the combination adjuvants, such as the choice of delivery platforms, the ratio of the components, and the best chemical linkers, if any, between adjuvants or adjuvants and the antigen(s).

Applications should include the following elements in order to be considered responsive to this FOA (Non-responsive applications will not be reviewed):

  • Adjuvants that have already shown immune boosting activity when used individually in licensed or unlicensed vaccines.
  • Exploration of the mechanism(s) of action of combination adjuvants that have already been shown individually to be effective in stimulating an enhanced immune response to vaccination when compared with antigen alone. These mechanisms may include, but are not limited to, stimulation of multiple immune receptors, or activation of multiple signaling pathways.
    • In vitro studies using human or other mammalian tissues, cells or molecules to determine the combination adjuvanticity to be effective in stimulating an enhanced immune response with enhanced efficacy.
    • In vivo animal testing of adjuvant combinations in vaccines, for safety, efficacy, and mechanisms of action studies.

In Vitro Studies: Use of human cells is encouraged, but not required. Examples of in vitro methods that could be used to determine the mechanisms of action and/or provide initial evidence of efficacy for the combination adjuvants include, but are not limited to:

  • Use of human and animal cell lines (e.g. the murine RAW macrophage cell line) with reporter genes under NF?B-control.
  • Use of primary human and animal macrophages or peripheral blood mononuclear cells (PBMC) to measure cytokine secretion in response to adjuvant combinations.
  • Studies of dendritic cell activation, antigen uptake, or signaling pathways in response to adjuvant combinations.    
  • Use of Toll-like receptor or RIG-I-like receptor reporter cell lines.

In Vivo Studies in Animal Models:  Proposed animal studies must be justified in terms of their relevance to human vaccination against infectious human pathogens. Examples of how animal models can be used to determine mechanism of action, efficacy, and safety include, but are not limited to:

  • Measurement of antibody production and antibody avidity
  • Studies of T cell and B cell function, e.g. cytokine production, lymphocyte subsets, and cytotoxic T cell assays
  • Pathogen challenge studies showing sterile protection or mitigation of disease.
  • Safety studies: measurement of serum levels of proinflammatory cytokines such as TNF-a and IL-1, or determination of weight loss, fever, or tissue damage to demonstrate improved immunogenicity without increased reactogenicity.

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 use only one adjuvant.
  • Clinical trials (the NIH definition of clinical trials is available at https://grants.nih.gov/grants/policy/hs/glossary.htm).  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 that include screening assays to identify adjuvants or adjuvant combinations.
  • Projects that do not provide evidence of immune boosting capabilities of each adjuvant.
  • 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 redirect or replace research aims during the funding period. Milestones will be negotiated after award, and NIAID may reduce the amount of the award for projects that do not achieve negotiated milestones.

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 of 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. Up to two additional staff from each award will also be allowed to attend the kick-off and annual meetings.

Annual site visits from NIAID program staff: the PI/PD 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
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIAID intends to commit $4.0 million in FY 2016 to fund 6-8 awards.

Award Budget

The application budget is limited to $350,000 in direct costs per year, and should reflect the actual needs of the project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is five years.

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.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

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)
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.

Required Registrations

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

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

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

  • To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
  • Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
  • Of an application with a changed grant activity code.
Section IV. Application and Submission Information
1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in 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.

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:

Lakshmi Ramachandra, M.Sc., Ph.D.
Telephone: 240-669-5061
Fax: 301-480-2408
Email: Ramachandral@niaid.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should include appropriate travel budgets to accommodate travel by the PD(s)/PI(s) and up to two key personnel to the initial meeting and subsequent annual meetings in Rockville, MD.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: List the broad, long range objectives and goals of the proposed project. Concisely and realistically describe the work to be completed.

Research Strategy: Within the research strategy, applicants must include the following:

  • Preliminary studies demonstrating the ability of each proposed individual adjuvant to enhance vaccine induced immunity. Evidence of enhanced immune response may be provided as unpublished data or by referring to the published literature.
  • Detailed plans for in vitro studies using human or other mammalian tissues, cells or molecules to determine the combination adjuvant’s mechanism(s) of action and obtain evidence consistent with enhanced efficacy.
  • Plans for in vivo animal testing of adjuvant combinations used with one or more vaccines, to study pre-clinical safety (low or no reactogenicity) and efficacy, as well as to further elucidate mechanism of action of adjuvants.
  • In addition to studying the mechanism of action of the combination adjuvant, some preliminary studies must be proposed to provide evidence of safety and efficacy using in vitro and animal model systems.
  • A clear description of interim objectives and draft quantitative annual milestones to be achieved during the project for assessing progress and success.

In addition, analysis of more than one adjuvant combination may be included. 

Letters of Support: Provide information with letters of support as needed, on how the PD/PI will obtain vaccines, antigens, proprietary materials, and reagents and clinical study samples.

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 submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
  • 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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. 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 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.

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.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information
1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

Will the proposed studies both elucidate mechanisms of action and promote the development of novel adjuvant combinations that provide vaccines with improved immunogenicity and address concerns related to reactogenicity?  

Investigator(s)

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? 

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? 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?

Are the proposed mechanistic studies appropriate and sufficient? Are the proposed in vitro studies designed appropriately to provide supportive evidence of efficacy of the proposed adjuvant combination? Do the proposed in vivo studies adequately examine safety and efficacy and are they justified in terms of their relevance to the combination adjuvant’s effects on human vaccination?

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?  

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?   

Additional Review Criteria

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children 

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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.

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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 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.
3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information
1. Award Notices

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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  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.

Cooperative Agreement Terms and Conditions of Award

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:

  • Monitoring the accomplishment of successful completion of milestones within the time frame and budget proposed.
  • Ensuring that results obtained from the Program are analyzed and published in a timely manner.
  • Cooperating with NIAID programmatic, technical, and administrative staff.
  • 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:

  • An NIAID Program Officer will be assigned to each award and will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Program Officer may also serve as a Project Scientist.
  • The role of the NIAID Project Scientist is to support and encourage the awardee's activities by substantial involvement as a partner and facilitator in the process without assuming responsibilities that remain with the PD(s)/PI(s). The NIAID Project Scientist will work closely with the PD/PI and other MMCA investigators to facilitate collaborations and to leverage the resources available to the Program.
  • The NIAID Project Scientist will monitor the progress of the awardees, help coordinate research approaches among all projects funded through the FOA, and contribute to the shaping of research projects or approaches as warranted. The Project Scientist will support and facilitate this process but will not direct it.
  • The NIAID Project Scientist will keep principal investigators informed about other ongoing studies supported by NIAID to avoid duplication of effort and encourage sharing/collaboration in immunology research.  The NIAID Project Scientist will coordinate access for the Program to other NIAID resources, as well as assist the research efforts of the Program by facilitating access to fiscal and intellectual resources provided by industry, private foundations, NIH intramural scientists and other federal government agencies as appropriate.
  • The NIAID Project Scientist will retain the option to recommend the withholding or reduction of support from any awardee that substantially fails to achieve its goals according to the milestones agreed upon between the PD/PI and the NIAID Program Officer, or fails to comply with the Terms and Conditions of the award.

Areas of Joint Responsibility include:

Milestones: 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

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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Wolfgang Leitner, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3575
Email: wleitner@niaid.nih.gov

Peer Review Contact(s)

Lakshmi Ramachandra, M.Sc., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)|
Telephone: 240-669-5061
Email: Ramachandral@niaid.nih.gov

Financial/Grants Management Contact(s)

Juan A. Rodriguez
National Institutes of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2956
Email: juan.rodriquez2@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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 and45 CFR Part 75.

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