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ID#: PA-11-333 (Companion FOA PA-11-334, R01 Research Project Grant)     Posted: 3 Jan 2012
Immunopathogenesis of HIV/AIDS-related Oral Manifestations and Host Immunity (R21)
Deadline: 16 Jun 2012
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Type of Grant: Research
Topics/Fields of Support: HIV persistence and latency, HIV transmission and acute infection, Innate immunity, Mucosal immunity
National Institutes of Health (NIH, NIDCR)

The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. For more than 60 years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world. NIAID is one of the 27 Institutes and Centers of the National Institutes of Health (NIH). NIH, like the Centers for Disease Control and Prevention (CDC), is part of the U. S. Department of Health and Human Services (HHS). NIH is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, please visit NIH (

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This Funding Opportunity Announcement (FOA) issued by the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health encourages R01 research projects that propose research on: i) immunopathogenic events that occur early in HIV infection, oral co-infections and AIDS-related oral opportunistic infections; ii) pathogen (viruses, bacteria, fungi) interactions in the oral cavity that induce lesions and exacerbate disease; iii) oral host immune responses (i.e., oral innate, mucosal and adaptive immunity linked to systemic immunity) to HIV infection, oral co-infections (viruses, bacteria, fungi) and oral opportunistic pathogen (viruses, bacteria, fungi) infections that lessen the pathogenic effects of infection, induce remission of oral lesions and diseases, or that occur in the midst of oral therapies and antiretroviral therapies; and iv) development and efficacy testing of novel treatments against oral pathogens and the induced immune responses generated. The goal is to generate knowledge to guide translational research focused on the development of novel, oral mucosal prophylactic HIV vaccines as well as therapeutic approaches against HIV, oral co-infections and oral opportunistic infections. The R21 mechanism intends to support early stages of high risk-high impact research that may lead to breaking new ground or extending previous discoveries.


The oral mucosa is one of the major sites for HIV penetration with infrequent transmission, but with potential for systemic spread. HIV infection is accompanied by AIDS-related oral manifestations, occurring in almost all cases worldwide. Even after the use of antiretroviral therapy, oral manifestations of HIV/AIDS still represent a significant public health problem. Based on this, it is essential to develop novel preventive and therapeutic approaches, including the design of safe and efficacious oral mucosal prophylactic HIV vaccines and innovative oral therapies against HIV, oral co-infecting pathogens and oral opportunistic infections. To develop these approaches, a comprehensive understanding of the immunopathogenic events that occur early during HIV infection and transmission, during co-infections with oral pathogens (viruses, bacteria, fungi), and during secondary infections caused by oral opportunistic pathogens (viruses, bacteria, fungi) is needed. A thorough understanding of oral HIV vaccine-induced and oral pathogen-induced innate, mucosal, and adaptive immune responses is also critical. These host responses are essential to blocking early events during infection and transmission, decreasing oral pathogen load, and containing infections in the oral cavity, and ultimately decreasing pathology and clinical manifestations.

From a pathogenesis perspective, progress has been made in understanding some aspects of the immunopathogenesis of HIV and its associated co-infections and opportunistic infections as well as in deciphering some elements of the host immune responses against these infections. For instance, general knowledge has been gained regarding the dual role of the oral mucosal epithelium acting as a barrier and as a main portal of pathogen entry; events that occur during oral mucosal infection, local dissemination and systemic transmission; and disease exacerbation by inflammation and laceration. From a prevention perspective, some studies conducted in animals and humans have shown that immune responses (innate, mucosal, and adaptive immunity) can be triggered with prophylactic HIV vaccines, including those delivered through the oral mucosa.

In spite of the knowledge gained about systemic HIV immunopathogenesis and the genital, rectal, and systemic immune responses induced by pathogens or prophylactic HIV vaccines, critical gaps still exist regarding: the oral immunopathogenesis of HIV, oral co-infections and AIDS-related oral opportunistic pathogen infections; and the host immune responses triggered by these oral pathogens or oral mucosal prophylactic HIV vaccines.

Research Topics

Studies considered appropriate for this FOA include, but are not limited to, those listed below.

  • Translate novel discoveries from structural biology, computational biology, bioinformatics, functional genomics, epigenomic modifications, physiology and systems biology approaches to better understand the oral immunopathogenesis of HIV and oral pathogens; delineate the balance between virulence and host immune response; define molecular networks to characterize HIV infection, disease progression and complication with oral pathogens; and define the oral and systemic host’s immune responses.
  • Use optimized in vitro and ex vivo systems, human and nonhuman models to evaluate the immunopathogenesis of HIV and oral pathogens, including: the initial events of pathogen entry into target cells of the oral mucosa; immunopathogenic consequences of oral pathogen translocation to the body; oral pathogen-pathogen interactions, and oral pathogen-host interactions that lead to the development of oral lesions and disease exacerbation; progressive changes in the oral cavity microenvironment (i.e., changes in the microbiome, viriome, mycobiome and host factors) upon infection, spread, disease progression, and treatment; and events that occur during abortive oral infections.
  • Use optimized functional and high throughput assays to enable understanding of HIV and oral pathogen immunopathogenesis and host immunity.
  • Elucidate protective, non-protective and deleterious pathogen and host factors in oral fluids and the oral mucosal epithelium that are important for HIV infection, co-infecting oral pathogens and oral opportunistic infections.
  • Characterize mechanisms of immune cell activation and host immune responses (i.e., oral innate, mucosal, and adaptive immunity linked to systemic immunity) against HIV and oral pathogens.  Especially, studies that: address the cross-talk between oral innate and adaptive immunity that confers protection against HIV and oral pathogens;  determine the correlates of immune protection upon oral prophylactic HIV vaccination; define oral-related mechanisms associated with the immune reconstitution inflammatory syndrome (IRIS); and  characterize oral immune networks and their connections with systemic immune networks triggered by oral mucosal prophylactic HIV vaccines or by oral co-infecting pathogens and opportunistic pathogens.
  • Characterize mechanisms of HIV and oral pathogens immune evasion and immune clearance.
  • Determine the interaction of HIV with oral pathogens (other viruses, bacteria and fungi) in disease exacerbation or in preventing infection.
  • Characterize oral polymicrobial biofilms linked to Oropharyngeal Candidiasis exacerbation, or used to guide the development of treatments for mixed oral pathogen infections.
  • Identify potential roles of mating, parasexual mating, and same sex mating of oropharyngeal Candida species to increase genome plasticity and pathogenicity.

The following topics will not be supported by this FOA:

  • Nasal, gastrointestinal (passing through the stomach to induce gut-associated host immune responses), rectal, or genital prophylactic HIV vaccines; enteric HIV vaccines delivered via the oral route; or exclusive focus on gastrointestinal, genital and rectal mucosal pathogenicity of HIV and gut-associated pathogens.
  • HIV, oral pathogen co-infections and oral opportunistic pathogen vaccine clinical trials, for which applications should be submitted to the FOAs titled: "Information Regarding Requests to Submit a Clinical Trial Planning Grant (R34)"; and "NIDCR Clinical Trial Implementation Cooperative Agreement (U01)".
  • Therapeutic HIV-, oral co-infecting pathogen-, oral opportunistic pathogen-, antigen-, adjuvant- and vector development-vaccine discovery, or non-vaccine prevention compounds.
  • Use of probiotics, vitamins, food supplements, and natural food products to enhance host immune responses.
  • Evaluation of oral and systemic tolerance.
  • Development and validation of immunoassays.
  • Behavioral research.
  • Research linking immunopathogenesis of HIV, oral co-infecting pathogens and AIDS-related oral opportunistic infections with the oral microbiome of non-human primates or other animal models.
  • Computational and bioinformatics analyses of published experimental data or based on text and database mining (i.e., secondary data analysis) without including primary experimental data production for HIV and oral pathogens.  Secondary data analysis grant applications should be submitted to the FOA titled "NIDCR Small Research Grants for Data Analysis and Statistical Methodology (R03)".

Eligible Organizations

Higher Education Institutions

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

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

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

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)


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


  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. 

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.


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TTY: 301-451-5939

Scientific/Research Contact(s)

Isaac R. Rodriguez-Chavez, Ph.D., M.S., M.H.S. 
Director, AIDS & Immunosuppression Program
National Institute of Dental & Craniofacial Research (NIDCR) 
6701 Democracy Boulevard, Room 614 
Bethesda, MD 20892-4878 
Telephone: 301-594-7985 

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Mary Daley Greenwood
Chief Grants Management Officer
National Institute of Dental and Craniofacial Research, NIH, HHS
6701 Democracy Boulevard
Room 658, MSC 4878
Bethesda, MD  20892-4878 (Courier 20817)
Phone: 301-594-4808