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

Of the 2.3 million new HIV infections globally per year, 30-40% occur in adolescents and young adults (15-24 years of age), with higher incidence in endemic areas. Although significant information is available on the socio-behavioral factors that lead to increased vulnerability of adolescents to HIV infection, knowledge about the contribution of mucosal adolescent biology is very limited. In mature adults, changes within the genital and GI mucosa, such as immune states, sexually-transmitted infections (STIs), hormonal-changes, etc., have shown associations to HIV susceptibility. However, results in adults cannot be extrapolated to adolescents since there are many differences in the adolescent anogenital tracts, including cellular structure, composition, tissue integrity, response to hormonal fluctuations, and immune system maturation.

In addition to age, there is an established epidemiological correlation between violence and HIV acquisition. However, very few studies have addressed the underlying biological mechanisms for this correlation. To fill this knowledge gap, studies in both adolescents and reproductive age adults are required to inform upon the biological, physiological, and pharmacologic factors that affect HIV susceptibility, following mucosal injury and/or the wound healing process.

Therefore, the purpose of this FOA is to stimulate biomedical research to identify how mucosal environment changes during normal anogenital maturation (adolescence), and/or injury across all ages, affects HIV susceptibility. The long-term goal of this FOA is to generate knowledge that will aid in the development of prevention modalities that are safe and effective in adolescents and in persons with mucosal injury.

Given the current state of the field, there is limited information regarding the state of the mucosal environment during reproductive maturation, tissue injury or wound repair, especially as it relates to HIV susceptibility. Therefore, this FOA will support hypothesis-generating (i.e. nonbiased approaches) to broadly characterize the mucosal environment in order to identify potential factors or conditions that may negatively or positively impact the mucosal environment. Support will be provided for studies using systems biology approaches, i.e. omics or cytokine arrays to generate descriptive data. Incorporation of hypothesis-generating studies is needed to address the relationships of anogenital maturational and injury effects on HIV susceptibility and the subsequent safety and efficacy of prevention products.

Given the high-risk nature of these hypothesis-generating studies, the structure of the RAIS includes a Research Operation Statement (ROS) that describes how the proposed research will lead to subsequent hypothesis-driven research on anogenital maturation and/or injury effects on HIV susceptibility. Investigators are encouraged to include the clinical expertise of pediatricians, trauma nurses etc., when formulating hypotheses and proposed studies, as appropriate.

For the purposes of this FOA:

• An adolescent is defined as a male or female, between the start of the 14th year to the end of the 18th, i.e. 14-19 years of age. Further, the terms adolescent, adolescence, age-related and age, are synonymous and may be used interchangeably within the context of this FOA.
• Injury is defined as anogenital injuries sustained from consensual coitus, sexual trauma due to assault, and cultural sexual or cleansing practices. Trauma is synonymous with injury.
• Wound healing is defined as the response to injury, including wound repair through resolution, post injury.

This FOA will support basic and applied research in the following areas of interest:

• Mucosal changes (immunological, hormonal, microbiome, wound healing) of the anogenital tract of female and male adolescents during reproductive maturation or injury and wound healing.
• Development of in vitro and animal models to study age-related and/or injury-specific responses and the accompanying wound healing process.
• Adolescent and/or injury-specific safety and efficacy studies with non-vaccine biomedical prevention (nBP) products and drug delivery systems using models of infection.
• In vivo imaging studies to measure and quantitate maturational, physiological and biochemical changes in the adolescent and/or wounded mucosa.
• Mechanistic studies of how the central or peripheral hypothalamic pituitary adrenal (HPA) and locus coeruleus-norepinephrine sympathetic adrenomedullary system (LC-NE/SAM) axes alter the mucosal environment as it relates to HIV susceptibility and mucosal injury/trauma and wound healing in the genital and GI tracts.

All examples of responsive areas of research assume that the identified activities are being conducted in the context of understanding mucosal changes that affect HIV transmission in the anogenital tract of 1) adolescents and/or following 2) mucosal injury (in all age groups). Applications that do not address mucosal changes in adolescents and/or following injury will be considered non-responsive and will NOT be reviewed.

Proposed studies may utilize human secretions, cells and/or tissues as well as in vitro and in vivo (animal) models of HIV transmission and acquisition.

Of specific interest are studies addressing:

• Maturational development and mucosal changes of the reproductive and GI compartments in adolescents and their relation to HIV acquisition including, but not limited to, how differences in the anogenital mucosa (architecture, tissue integrity, epithelial thickness and maturation, immune composition, drug metabolism, hormonal changes, race, ethnicity, etc.) contribute to HIV susceptibility and/or alter the safety and efficacy of non-vaccine biomedical prevention strategies (nBPs).
• Injury and subsequent wound healing as modifiers of the mucosal environment in the anogenital tracts, and their relationship to HIV susceptibility and nBP candidate/strategy safety and efficacy. Of particular interest are longitudinal wound healing studies of the anogenital mucosa from initial wounding to wound resolution and how repeated injury and wound healing alter the mucosa and HIV susceptibility. Trauma/injury and wound healing studies may be conducted across populations, and need not be limited just to adolescents. It is recommended that applicants proposing human subjects research involving measurements of trauma and wound healing have clear temporal records of traumatic incidence.

Additional examples of responsive areas of research include:

• Immunological studies of the anogenital mucosa in adolescents and/or following injury. Studies may include, but are not limited to, alterations in HIV target cell homing, trafficking, turn-over and activation, responses of pattern recognition receptors, inflammasome activation and subsequent genomic, proteomic and phenotypic and locality changes of these cells.
• Specific microbiome changes within the mucosa during maturation, following injury or wound healing.
• The role of genital secretions and hormones, including the influence of the menstrual cycle and prostate secretions on the anogenital mucosa in the adolescent or injured/traumatized tissue, and how these alter susceptibility to HIV infection/susceptibility.
• Understanding the interaction of preventive agents and their vehicles (devices, formulations/excipients) with adolescent anogenital tissues. Of interest are the effects on product pharmacokinetics (PK) and pharmacodynamics (PD). This may include investigations of drug transporter expression and modulation in target mucosal tissues as well as nBP-induced mucosal tissue changes in adolescent or injured/traumatized anogenital mucosa.
• Development of animal models for studying adolescent and mucosal injury and wound healing, including models representing adolescent anogenital mucosa development, coital models or others to mimic sexual trauma, age, hormonal and immune status. Sufficient numbers of animals should be included in all groups to allow for endpoint statistical analysis. Applicants are cautioned that underpowered studies can reduce reviewer enthusiasm for the application.
• Development, adaption and engineering of hardware and/or software solutions that will afford for novel approaches to analyzing the cellular, tissue and systemic effects on the anogenital mucosa and injury in vitro, in vivo and ex vivo. Engineering adaptions can encompass a wide range of development processes focused on creating solutions to quantitatively and dynamically analyze responses to injury and/or age-related changes in cells and/or tissues.
• Studies addressing the HPA and LC-NE/SAM axes and their mechanistic effect on the anogenital mucosal environment. Emphasis is placed on the effects and variations of these pathways on severity of injury and resolution (wound healing) of genital and GI mucosa.

Applications focusing on the following areas will be considered non-responsive and will NOT be reviewed:

Basic science-oriented research projects that focus on the mechanisms of, or earliest events in, HIV/SIV transmission in the absence of adolescents, injury, or wound healing. Behavioral studies or programs, unless they comprise a limited part of the research and are solely to inform upon the predominantly biomedical studies proposed in the application.

Other specific types of research that will be considered non-responsive:

• Studies focused on mucosal environment changes, injury or wound healing at sites other than the anogenital tracts. This includes, but is not limited to, the skin and upper respiratory tract (e.g. lung, tonsils, oral cavity, nasopharynx, etc.).
• Development or modification of in vitro or animal models that are not focused on understanding the role of adolescence, injury or wound healing on HIV susceptibility.
• Applications proposing any clinical trials or first in-human testing. Clinical research that uses specimens from clinical studies or epidemiological cohort(s) may be supported under this FOA. Applicants are strongly urged to discuss any application that might be identified as a clinical trial or intervention in human subjects with NIAID staff prior to submission.
• Given limited adolescent participation and limited information availability regarding sexual violence (outside of product usage), applications that propose the use of stored or archived samples from previous or on-going prevention studies, i.e. Partners in PrEP, CAPRISA 004, FACTS, VOICE, ASPIRE, FEM-PrEP etc., will be considered non-responsive.
• Development of new nBP prevention products, including but not limited to: new topical or systemic microbicides, PrEP agents, multipurpose prevention technology (MPT) agents/strategies or any nBP strategy designed to prevent HIV or STI transmission (i.e. drug discovery and development). Development of new agents and strategies includes optimization and/or alterations of dosing and delivery formats.
• Any form of vaccine development (new mucosal vaccine, vector (bacterial or viral), insert, or delivery system) or research.
• Physical modification of prevention products and/or strategies that have been, or are currently in, clinical trial testing or proposed for clinical testing, to enable small animal research, safety or efficacy testing.
• Studies which focus solely on the use of agents known to be cytotoxic to mucosal tissues, such as Nonoxynol-9 or microbicide products/candidates demonstrated to have caused harm in preclinical animal toxicology studies and/or clinical efficacy or safety trials. These agents may be used, however, as positive controls with the appropriate negative controls, in efforts to delineate the upper and lower response boundaries of a proposed effect.
• Studies using any contraceptive or non-specific HIV-prevention modality, including spermicidal products and mechanical barriers.
• Applications proposing to assess the effect of STIs that have not been shown through clinical and epidemiological investigations to be associated with increased susceptibility or acquisition of HIV infection.
• Use of beneficial bacteria, probiotics and/or bacterial drug delivery systems as a means to treat or modify microbiome imbalances, change the anogenital mucosa or HIV susceptibility and/or deliver an active pharmaceutical ingredient (API).
• Behavioral and social science studies on adolescents and injury designed to prevent or modify behaviors or cultural preferences that predispose adolescents to HIV acquisition or sexual violence resulting in mucosal injury.
• Behavioral and social studies related to the central or peripheral hypothalamic pituitary adrenal (HPA) and locus coeruleus-norepinephrine sympathetic adrenomedullary system (LC-NE/SAM), or other axes. Biomedical studies to gain further knowledge of these axes. Direct biomedical studies to elucidate these axes, assay improvement or development, identification or optimization of current or new biomarkers for peripheral or central stress responses and studies to differentiate stress types (i.e. acute, chronic).
• Community-based assessments, surveys or canvasing, retrospective or prospective clinical assessments to provide epidemiological data to measure incidence of violence. Studies to determine the impact of violence intervention strategies.

Applicants are encouraged to contact the NIAID Scientific/Research Contacts to determine responsiveness of proposed research designs prior to application submission. Applicants are also encouraged to consult with local IRBs during application development to determine the feasibility of the proposed research. NIAID reserves the right to terminate or down-negotiate the scope and budget of awards that subsequently do not receive IRB approval to conduct the proposed research.

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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not 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.

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.

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

This FOA encourages multi-disciplinary research: investigators are encouraged to include the clinical expertise of pediatricians, trauma nurses, etc., when formulating hypotheses and proposed studies, as appropriate.

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

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

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

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

Research Strategy:

Research Operation Statement (ROS)

Given that applications responding to this FOA may include hypothesis-generating studies that may be considered high-risk, all applicants must provide a concise ROS for the proposed research which addresses either proposed next step hypothesis-driven research and/or the integration into subsequent specific aims which build on hypothesis-generating research.

The ROS should be explicitly identified as the Research Operations Statement in the application text. The applicant should specifically address the following in the ROS:

• How the proposed research addresses the gaps in our understanding of how anogenital mucosal injury or wound repair or reproductive maturation impacts HIV susceptibility. Projects may focus on these topics individually or in combination;
• How knowledge gained by the proposed studies (hypothesis-generating in particular) will be used to develop specific research questions, hypotheses and future studies;
• How proposed studies and potential results will lead to the development of novel "mucosal friendly" prevention strategies in adolescents and in the presence of injured tissue.

Use of Vulnerable Populations of Research Subjects

For applications that involve collection of tissues and secretions from adolescents, applicants should discuss whether the appropriate state laws and IRBs have been consulted in order to determine potential barriers to the proposed research. NIAID reserves the right to terminate or down-negotiate the scope and budget of awards that subsequently do not receive IRB approval to conduct the proposed research.

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

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

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

When conducting clinical research, follow all instructions for completing 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.

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.

For this particular announcement, note the following:

The R01-based RAIS program is intended to support high-risk, biomedical research efforts towards a better understanding of the adolescent male and female genital and GI mucosal environments. Specifically, the goal is to address how anogenital maturation and/or injury or wound repair alters the mucosal environment at HIV susceptible sites. This information is essential to the NIH mission to provide the safest and most efficacious microbicides and Pre-Exposure Prophylaxis (PrEP) strategies to populations at heightened risk of HIV infection.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is the proposed research relevant to understanding the impact of age (adolescent), injury and/or wound repair on the anogenital mucosa and its role on HIV susceptibility?

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? If supporting experts or clinicians (e.g. pediatricians, trauma nurses, etc.) are included in the application as investigators or collaborators, do they have the appropriate expertise to add value to the proposed research?

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?

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? If the proposed research involves collection of tissues and secretions from adolescents, have the appropriate state laws and IRBs been consulted to determine if there are any barriers to the proposed research?

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.

Research Operational Statement (ROS)

Does the proposed research address the gaps in our understanding of how mucosal changes due to reproductive maturation or injury or wound repair (individual focus or programs that combine these topics) impact HIV susceptibility? Does the application outline how knowledge gained by the proposed studies (hypothesis-generating in particular) will be used to develop specific research questions, hypotheses and future studies? Can the proposed studies and potential results lead to the development of novel "mucosal friendly" prevention strategies in adolescents or injured mucosa?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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 the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

Kristen A. Porter, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4783
Email: porterka@niaid.nih.gov

Jim A. Turpin, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2732
Email: jturpin@niaid.nih.gov

Fulvia Veronese, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-4148
Email: veronesf@niaid.nih.gov

Lisa Begg, Dr.P.H., R.N.
Office of Research on Women’s Health (ORWH)
Telephone: 301-496-3975
Email: beggl@od.nih.gov

Robert Freund, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1050
Email: freundr@csr.nih.gov

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@niaid.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 .