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.

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

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

The purpose of the Funding Opportunity Announcement (FOA) is to support research to advance current knowledge of the developing immune system during the first year of life and to encourage innovative approaches to understand the distinctive characteristics of neonatal/infant immune responses. Applications are sought that will examine the development and function of the immune system of neonates (0-28 days) and infants (29 days 12 months), in order to discover and define immune mechanisms, mediators, cells, and pathways that are involved in immune development, immune protection, and immune regulation in response to commensal bacteria, allergens, infectious agents (including HIV), vaccines, or environmental pollutants. This program encourages the use of innovative approaches using human infant tissues and cells, or relevant animal models, to define pathways and mechanisms that contribute to the immune status of the neonate and infant. Innovative studies that break new ground or extend discoveries toward new directions are encouraged. To encourage new approaches or hypotheses, preliminary data or a proven record of accomplishments in infant immunology is not required, although demonstration of feasibility to accomplish the proposed research is required. The ultimate goal of this program is to expand our understanding and knowledge of early immune system development, which will provide foundational information for future studies to improve immune health and vaccine efficacy in this critical age group.

Infant mortality continues to be a major global health problem. In 2013, the World Health Organization (WHO) estimated worldwide infant mortality at 4.6 million deaths. Of these, 23% of neonatal deaths were due to infections such as sepsis, meningitis, pneumonia, tetanus, and diarrheal diseases. Newborns and infants have a higher susceptibility to severe infections than adults due to functional differences in their immune system, many of which are not well understood. In HIV-exposed infants, the risk of severe secondary infection is even greater, especially for acute respiratory infections, which are the leading cause of mortality in this population. Despite the availability of vaccines for a variety of infectious diseases, infants exhibit a reduced ability to generate long-lived protective immunity in response to vaccination. It is now known that allergic diseases, the most common chronic conditions of childhood, begin early in infancy. Recent intriguing observations, which suggest that early exposure to allergens may protect infants from development of allergic diseases, warrant careful investigations into the early development of the human immune system. Finally, environmental exposure to toxins has the potential to further impair or alter immune function in neonates and infants.

The NIH is committed to improving the health of neonates and infants and have supported numerous programs, spanning several decades, that include cohorts of infants or young children in the areas of: allergy and asthma (http://www.niaid.nih.gov/about/organization/dait/programs/Pages/allergyAsthma.aspx); transplantation (https://www.ctotc.org/); vaccine and anti-viral development (http://www.niaid.nih.gov/about/organization/dmid/researchers/clinical/vteu/Pages/default.aspx and https://www.nichd.nih.gov/research/supported/pages/impaact.aspx); and human immune profiling (http://www.immuneprofiling.org/hipc/page/show). However, a deeper understanding of the basic mechanisms controlling immune system development and function in both healthy and HIV-infected neonates and infants is still needed to improve overall immune function and further the development of vaccines and immune-based therapeutics for these vulnerable populations.

Neonatal immune responses differ in multiple ways from adult patterns, reflecting both the orderly development of defenses to pathogens and the establishment of tolerance to normal flora, foods, and other innocuous molecules in the environment. There remains incomplete understanding of the mechanisms involved in these processes. Innate immune responses of neonates and infants are less robust than older individuals and exhibit such characteristics as: decreased Toll-like Receptor (TLR) signaling and diminished cytokine production; less potent dendritic cell, natural killer cell, and neutrophil function; and reduced complement system activity. The adaptive immune system is dominated by Th17 cells in the neonatal period and Th2 responses during the remainder of infancy, with diminished Th1 responses during the first year of life. Poor responses to T-independent antigens require the use of protein-conjugated polysaccharide vaccines in the very young. In addition, neonatal antibody responses are delayed, less durable, and of lesser magnitude than those seen in adults.

Microbiome colonization and early encounters with infectious agents, allergens, and/or environmental toxins may shape the overall characteristics of immunity in childhood and, in some instances, for the rest of the human lifespan. Several factors influence initial establishment of the microbiome, including mode of delivery (vaginal versus caesarean) and breast versus formula feeding. HIV infection acquired during infancy also induces dysfunction upon the vulnerable infant immune system. Infants who are perinatally infected with HIV experience high viral loads, lack of control of viremia, and rapid disease progression compared to adults infected with HIV. In regard to allergy, a recent study found that controlled, early introduction of dietary peanut in high-risk infants prevents the development of peanut allergy, demonstrating the need for a deeper understanding of oral tolerance mechanisms in infants. Studies also have reported associations between environmental exposures to pollutants and altered immune function. Exposure to polychlorinated biphenyls (PCBs) during the developmental years has been associated with a decrease in antibody concentrations following vaccination in children in the Faroe Islands, with those in the first years of life being especially vulnerable. Air pollution is associated with immune system alterations and a higher incidence of respiratory infections. However, the mechanisms by which environmental exposures to pollutants alter basic, infant immunological processes remain largely unknown.

The prior funding period of the Immunity in Neonates and Infants program (2012 -2017) supported fifteen R01 grants to conduct studies to enhance the understanding of immune function and development during the first year of life. While these groups have made significant progress, more research is needed to elucidate the mechanisms that drive immune development and function in early life. Studies supported by this reissued FOA and the prior FOA will lay the foundation for targeted strategies to protect neonates and infants from infections (including HIV), to prevent allergic and other immune-mediated diseases, and to understand early life immune parameters that may modify susceptibility to infections later in life.

This initiative will support research projects focused on defining the fundamental aspects of immune system development in neonates and/or infants (via animal models and/or human studies) and on elucidating the immunoregulatory mechanisms involved in activating, suppressing, and/or sustaining a protective immune response elicited by: nonpathogenic/commensal microorganisms; natural infections; licensed vaccines or candidate vaccines in which the vaccine clinical trial is funded by other mechanisms; allergens or therapeutic approaches to prevent allergy; and/or environmental exposure to pollutants/toxins. The populations of interest for this FOA are healthy, full-term neonates and infants [neonates (0-28 days) and infants (29 days 12 months)] as well as HIV-infected neonates/infants. Studies in premature infants may be done as a comparison to full-term infants. For studies related to the development of allergic immune responses, investigations comparing high risk to non-high risk infants are encouraged. Studies may use cell and tissue samples collected from subjects recruited specifically for this project or use human samples that are obtained from independently-funded clinical trials. Animal models also may be considered for the FOA, since animal studies permit mechanistic analyses that provide insights into immune responses at the organ and tissue level that may be difficult or impossible to conduct in humans. Given the current state of knowledge regarding infant immune development, descriptive studies are acceptable. This initiative will support hypothesis-driven and descriptive studies. Innovative studies that break new ground or extend discoveries toward new directions are encouraged. Applicants proposing advanced studies or submitting renewal applications are expected to provide relevant preliminary data or a progress report, respectively, as a basis for the proposed experiments.

To promote rapid public access to data and results, all investigators supported under this FOA will be expected to share their supported data publicly through ImmPort (https://immport.niaid.nih.gov/immportWeb/home/home.do?loginType=full) or other public portals designated by NIH, consistent with achieving the goals of the program. Data set definitions, safeguarding content and schedules for data sharing will be negotiated with NIH prior to award and data collection, as will plans for other resource sharing. If further schedule changes are needed throughout the funding period, they will be negotiated with NIH after evaluation by the Steering Committee.

Funding beyond the first year may be negotiated downward depending on the progress in meeting the data- and other resource-sharing plans negotiated with NIH after award, consistent with achieving the goals of the program.

Steering Committee

A Steering Committee will be established to serve as the governing board of the Immunity in Neonates and Infants program and to facilitate multidisciplinary approaches that advance this area of research. The Steering Committee will promote scientific collaboration, exchange of scientific findings among the funded investigators, and coordination of data dissemination to the broader scientific community.

In order to understand fundamental aspects of immune system development and function in neonates and infants (animal models and human studies) and to define the regulatory mechanisms involved in activating, suppressing, and/or sustaining an immune response triggered by natural infections; licensed vaccines or candidate vaccines in which the vaccine clinical trial is funded by other mechanisms; allergens or therapeutic approaches to prevent allergy; and/or environmental exposure to pollutants/toxins, research areas of interest include, but are not limited to:

• Mechanisms controlling innate immune function, including:
• Innate immune receptor signaling and cell function (cytokine production, lytic activity, phagocytosis, etc.)
• Complement activation and function
• Impact of sex differences on innate immune development and function
• Role and mechanisms of action of adjuvants/immune-potentiating molecules or compounds for improving protective immune responses in neonates and infants
• Adaptive immunity, including:
• Regulation of Th17 and Th2 bias, and suppression of Th1 responses
• Development and function of regulatory T cells
• Regulation of B and T cell memory development and maintenance
• Impact of sex differences on adaptive immune development and function
• Mechanism of oral tolerance in neonates/infants
• Mechanism(s) by which maternal antibodies impact neonatal/infant immune development and function
• Understanding the influence of specific tissue microenvironments on immune development, including unique features of tissue-specific innate and/or adaptive immune responses to allergens, infection, vaccination, pollutants or toxins.
• Microbiome:
• Mechanistic role of microbiota in shaping the immune response in early life
• Impact of interactions between microbiota at different sites (oral, skin, gut, respiratory, etc.) on immune system development and function
• Effect of early life encounters (infections, vaccines, allergens, pollutants, toxins) on neonatal/infant immunity, including:
• Mechanistic understanding of the effect(s) of environmental exposures on the functionality of the developing neonatal/infant immune system
• The effect of prenatal/maternal environmental exposures on infant immune function, including the persistence of immune effects later in life.
• The persistence of immune effects of prenatal/maternal/neonatal exposures on susceptibility to infections or immune-mediated diseases later in life
• HIV:
• Host cellular factors and their function(s) in the maintenance of HIV infection
• Mechanisms for development of broadly neutralizing antibodies in neonates during the perinatal period
• Role of innate-adaptive interface interactions in HIV infection
• Mechanism of immune tolerance in neonates and its role in perinatal HIV infection

NICHD will support projects focused only on AIDS-related topics.

This FOA will not support research in the following areas. Applications proposing these topics will be considered non-responsive and will not be reviewed:

• Studies in: infants with known genetic abnormalities, including primary immunodeficiencies; infants undergoing cancer chemotherapy; infants who are undergoing transplantation procedures; infants with autoimmune diseases, or receiving immunosuppressive therapy; and infants infected in utero, perinatally, or neonatally with hepatitis B virus, Treponema pallidum (syphilis), Toxoplasma gondii, rubella virus, cytomegalovirus, or herpes simplex virus.
• Studies that focus on non-immune mechanisms of infectious diseases (e.g. transmission, carriage, pathogenesis, or vaccine development/testing) instead of immunological response mechanisms in infants or neonates.
• Studies on exposures to: alcohol, chemotherapeutic agents, radiation which is not a result of an ambient environmental exposure, drugs of abuse, and pharmaceuticals.
• Clinical trials. However, samples from completed clinical trials or clinical trials supported by other mechanisms, or samples obtained from human subjects immunized with licensed vaccines, where the vaccine is administered according to the product label instructions, may be used. A definition of clinical trials is available at http://grants.nih.gov/policy/hs/glossary.htm.
• Epidemiological studies.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

Applicants must obtain 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.

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.

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:

Nancy V zquez-Maldonado, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5044
Email: nvazquez@niaid.nih.gov

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

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

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

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

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

Other Attachments: The following items should be included as attachments under "Other Attachments"

A memorandum of understanding (MOU) from the clinical trial sponsor(s), IND holder(s), and PD(s)/PI(s) must be provided by applicants if clinical samples will be obtained from ongoing clinical trials for projects proposed under this FOA.

Applicants obtaining samples from an independently funded clinical trial(s) must include a memorandum of understanding to confirm agreement among the various parties that outlines their expectations of the agreement in the following areas: (1) ownership, analysis, access, and release of data from the proposed infant immunity studies; (2) access to the data from the parent clinical trial (how/when) that is needed to analyze the data generated by the proposed infant immunity studies, including procedures for prevention of unblinding of the parent trial; (3) documentation of quality assurance procedures for both the parent clinical trial and the proposed infant immunity studies, and documentation of data and safety monitoring procedures for the parent clinical trial, especially for efficacy trials; (4) intellectual property management; and (5) publication of the proposed infant immunity study results.

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

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

Applicants must include travel costs for the PD(s)/PI(s) and key personnel to attend one, one and a half day Programmatic Steering Committee meeting per year to be held in the Bethesda, MD area.

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

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

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

Specific Aims. Provide a brief description of the specific aims to be accomplished by the proposed study.

Research Strategy. Applicants should summarize the scientific problem being addressed and how the proposed research fulfills the purpose and objectives of this FOA. Describe the potential gain in fundamental knowledge of neonatal and infant immune development and function. Describe the novelty or innovation of the research in terms of how the outcome will lead to new and potentially transformative discoveries in infant immune development. In addition to the description of proposed studies, applicants must provide a plan for management and quality control of data for the proposed study, and include the statistical design (including power calculations) and analysis plan for the proposed human and/or animal studies. Additionally, applicants should demonstrate feasibility and experience with the proposed approach.

Applications that involve animal models must include justification for the use of the proposed models with respect to the relevance to human neonates or infants. Specifically, applicants should describe how the developmental stage of the proposed animal model corresponds to developmental stages of human neonates (0-28 days) or human infants (29 days - 12 months).

Protection of Human Subjects: For projects proposing the use of human samples to be obtained from independently-funded clinical trials, include:

• synopsis of the parent clinical trial protocol
• informed consent forms for ongoing or completed parent clinical trials only (i.e., not applicable for clinical trials that have not completed IRB review at the time of application submission).
• informed consent forms for the proposed immune profile studies, if different from the parent trial; draft forms are acceptable
• reference to the ClinicalTrials.gov citation, if applicable
• table of events including the volume of blood, or amount of tissue, collected for the proposed neonate/infant immunity studies (needed from completed clinical trials or clinical trials supported by other mechanisms, or samples obtained from human subjects immunized with licensed vaccines)

Note: If permission for obtaining additional samples is not included in the parent clinical trial’s consent form, then the applicant needs to explain how consent will be obtained.

To the extent permitted by applicable laws and regulations, NIH will treat as confidential trial information that the trial sponsor deems proprietary. Copies of the informed consent form(s) or draft informed consent form(s) for the proposed additional studies, if different, must also be included. It is recommended that applications submitted under this FOA have clear language in the informed consent form(s) or draft informed consent form(s) that distinguishes proposed neonate/infant immune studies from the clinical trials with which they are linked. It is also recommended that the following items be clarified in the consent form or draft informed consent form(s): (1) additional blood or tissue that will be collected as part of the proposed study; (2) the right of the subjects to refuse to participate in the proposed study and still participate in the parent clinical trial; (3) that no charges to the subject for participation in the proposed study are incurred; and (4) agreement to share the subject’s de-identified data obtained from the proposed study as well as the parent trial. Any incentives provided to subjects to participate in the proposed study, if in addition to those under the parent clinical trial, should be clearly described and justified.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All investigators funded under this FOA will be expected to share their data publicly through ImmPort or other public portals approved by NIH.

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

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

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

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

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

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

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

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

For hypothesis-generating/descriptive studies: do they lay a foundation that may lead to the discovery of novel phenomena, major advances or innovative studies in the future? For mature projects: to what extent do the proposed studies suggest and explore creative, original, or potentially transformative concepts in understanding neonatal and infant immune development function?

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

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

Are sufficient numbers of subjects included and are the plans for subject recruitment feasible? Is the sample size adequate for data interpretation? Are the source and procedures for the collection of clinical samples clearly described and are all the logistics and feasibility issues addressed and adequately justified? For applicants new to the field, is the description of project feasibility and experience with the proposed techniques adequate? Are the plans for management and quality control of data for the proposed study described and feasible?

For projects involving animal models: 1) are sufficient numbers of animals included; 2) does the developmental stage of the proposed animal model correspond to the same developmental stage of human neonates (0-28 days) or human infants (29 days-12 months); and 3) is the animal model justified in terms of its relevance to human responses and the scientific goals and research strategy proposed?

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

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

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

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

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

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

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

Not Applicable

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

Not Applicable

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

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

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council or Board. The following will be considered in making funding decisions:

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

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

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, 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.

To assist in the overall evaluation of the research program, all awardees will participate in annual one and a half day program progress meetings arranged by the NIH Program Officer, to be held after award in the Bethesda, MD area. The purpose of these annual meetings is to discuss individual program progress and foster collaborations among the funded investigators. The program progress meetings are open to investigators supported under this FOA and to NIH extramural staff.

The PD(s)/PI(s) will have the primary responsibility to:

• Serve as a voting member on the Steering Committee (SC); participate in SC activities and accept and implement the policies and procedures developed by majority vote of the Steering Committee.
• Work closely with NIH staff in the scientific, technical, and administrative management of this program.
• Ensure data from individual projects are made publicly available, following the timeline, data set definitions, and procedures negotiated at the time of Award and included as a Term and Condition of Award. Data set definitions will be negotiated with NIH as part of the data-sharing plan for the program.
• Share reagents and resources with other investigators funded under this FOA as appropriate and consistent with achieving the goals of the program.
• Share all data generated under this FOA publicly through ImmPort or other public portals designated by NIH as appropriate. Data submission and release plans will be negotiated prior to award. The PD/PI will establish procedures within the project to ensure that all members of the program support and conform to the data-sharing and other resource-sharing plans. The final versions of NIH-approved sharing plans will become a condition of the award.

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

NIH Project Scientists will have substantial programmatic involvement as described below:

• Provide input into the design of research activities.
• Coordinate NIH staff assistance, including participation in periodic on-site monitoring with respect to compliance with Federal regulations, quality control, accuracy of data recording, sample accrual, etc.
• Evaluate the adequacy of data-sharing and other resource-sharing plans when making funding recommendations. NIH program staff may require modifications of sharing plans with the applicant.
• Ensure that all funded investigators conform to the data-sharing and other resource-sharing policies.
• Participate in investigator and Steering Committee meetings.
• Facilitate collaborations with and access to other NIH-supported research resources and services.
• Advise in project management and technical performance.
• Facilitate interactions among investigators and with ImmPort staff and promote compliance of members with the schedules for data- and other resource-sharing.
• Serve as a resource for scientific and policy information related to the goals of the awardees research.
• Have confidential access to data generated under this Cooperative Agreement, for use in the preparation of internal reports on the activities of the awardees.
• Promote coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.
• Provide advice to the awardees with regard to:
• Compliance with Federal regulations
• Oversight and monitoring of collaborative research
• Feasibility of timely progress towards completion of planned activities
• Plans for incorporation of new technologies or other resources
• NIH staff may appoint other investigators as non-voting members to provide additional expertise and perspective.

Additionally, an agency program official or IC program director, which may be the same as the project scientist, 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:

Steering Committee: The Steering Committee of the Immunity in Neonates and Infants program will coordinate and facilitate research activities for the overall program; ensure close coordination with the ImmPort database; facilitate compliance with the data- and other resource-sharing policies; and promote optimal research flexibility, synergy, and efficiency. The Steering Committee will include the PD/PI from each awarded U01 as a voting member and the NIH Program Officers as non-voting members. Awardees will be expected to collaborate, share reagents, assays, animal models, human samples, and experimental results that would facilitate the research activities of other members.

• Steering Committee Responsibilities:
• Evaluate progress and provide guidance to investigators of the individual research projects.
• Establish protocols for the review and modification of ongoing studies, which may include recommendations for new collaborations or resource allocations among the members.
• Coordinate resource sharing among the awardees as appropriate.
• Assist as required in preparing formal reports summarizing activities and/or progress within the Immunity in Neonates and Infants network.
• Review schedules for submission of U01-generated data and data analyses from each project for public dissemination.
• Define procedures for the publication and/or oral presentation of results or data collected collaboratively within the program.
• Establish subcommittees and working groups with discrete responsibilities and authorities to promote infant immunity research, interactions with the ImmPort database, and priority setting.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

A final 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.

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Mercy PrabhuDas, Ph.D., M.B.A.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3534
Email: mprabhudas@mail.nih.gov

Devasena Gnanashanmugam, M.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-3761
Email: Devasena.gnanashanmugam@nih.gov

Melody Mills, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3318
Email: millsm@niaid.nih.gov

Michael C. Humble, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-316-4621
Email: humble@niehs.nih.gov

Leah Miller, Ph.D., M.B.A.
Office of Research on Women’s Health (ORWH)
Telephone: 301-402-1770
Email: leah.miller@nih.gov

Denise A. Russo, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6871
Email: drusso1@mail.nih.gov

Nancy V zquez-Maldonado, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5044
Email: nvazquez@niaid.nih.gov

Philip Smith
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2948
Email: philip.smith2@nih.gov

James Williams
National Institute of Environmental Health Science (NIEHS)
Telephone: 919-541-1403
Email: williamsjr@niehs.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clark1@mail.nih.gov

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

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