September 2009 DAIDS Council-Approved Concepts

NB: Concepts represent early planning stages for PAs, RFAs, or solicitations for Council's input. Council approval does not guarantee that a concept will become an initiative.

If NIAID publishes an initiative from one of these concepts, we link to it below. For a full list of initiatives, go to NIH Funding Opportunities Relevant to NIAID.

Table of Contents

• Microbicide Innovation Program for Topical Microbicides
• Methods for Prevention Packages Program
• Integrated Preclinical/Clinical AIDS Vaccine Development Program
• Consortia for AIDS Vaccine Research in Nonhuman Primates

Microbicide Innovation Program for Topical Microbicides

Request for Applications

Contact: Jim Turpin
Phone: 301-451-2732
Email: JTurpin@niaid.nih.gov

Objective: The specific objectives of the Microbicide Innovation Program are:

• Development of new microbicide approaches and additional rational targets through preclinical and basic research.
• Discovery and characterization of microbicides (singly or in combinations) directed against HIV or sexually transmitted infections (STIs) that are linked to HIV acquisition.
• Identification and promotion of emerging technologies or models that can contribute to the development of new and/or more efficient ways of assessing microbicide safety, efficacy, and acceptability.
• Design of complex prevention strategies that incorporate vaginal, rectal, and/or penile applied microbicides in the context of other prevention strategies.
• Support of novel topical microbicide formulation strategies, including long-lasting and coitally-disassociated formulations and delivery systems.

Description: This initiative supports a broad range of research to maintain a vibrant HIV topical microbicide pipeline:

• Discovery of new single and combination vaginal, penile, and rectal microbicides.
• Development of dual action microbicides against HIV and STIs associated with HIV acquisition.
• Proof-of-feasibility and -concept for microbicide candidates or strategies.
• Identification, characterization, and development of new microbicide targets.
• Formulation and/or delivery strategies of new microbicides with the aim of creating longer lasting and coital disassociated microbicides.
• Development and validation of new in vitro and in vivo assays, technologies, and/or devices to assist in microbicide lead study, discovery, and development.
• Safety and efficacy of new animal models.
• Elucidation of the role of innate and adaptive mucosal immunity in microbicide safety and efficacy.
• Exploration of the modulation of vaginal, rectal, and penile mucosal  immunity as a microbicide strategy.
• Behavioral and social studies aimed at linking biophysical microbicide and formulation properties with acceptability and adherence.

Methods for Prevention Packages Program

Request for Applications

Contact: Vanessa Elharrar
Phone: 301-827-0845
Email: elharrarva@niaid.nih.gov

Objective: The objectives will be for investigators to:

• Devise optimal "prevention packages" (combination interventions) for specific populations for different routes of transmission and risk factors for HIV transmission.
• Demonstrate that the proposed prevention package is acceptable to the target population and the study design is appropriate and feasible.
• Design protocols to test the safety and efficacy of the prevention packages in the target population.

Description: This project will support:

1. Collaborations between behavioral and biomedical (clinical) scientists, epidemiologists, and clinical trial design specialists to develop new strategies and methodologies to facilitate the design of HIV prevention trials that combine multiple prevention interventions.
2. A systematic review and meta-analysis of existing prevention research data germane to the chosen target population(s). These data can be used to develop a mathematical model for assessing the impact of various intervention combinations shown to reduce HIV incidence in the same or similar settings. 
3. The design of prevention packages that optimally include both biomedical and behavioral interventions applicable in a complementary manner to the target population. 
4. Conduct of a pilot study to demonstrate acceptability of the package to the target population. The research should be designed to be operationally feasible with potential to provide a conclusive assessment of the prevention package's safety and efficacy.
5. Development of a clinical trial protocol to test the safety and efficacy of a prevention package in a specific population.

Integrated Preclinical/Clinical AIDS Vaccine Development Program

Program Announcement Identifying Location of Peer Review

Contact: Michael Pensiero
Phone: 301-435-3749
Email: mpensiero@niaid.nih.gov

Objective: This initiative will identify and accelerate the advancement of safe, novel, and promising prophylactic HIV vaccine candidates and support the development of clinical research reagents to answer specific scientific questions that can be addressed only through human clinical studies.

Description: The IPCAVD program supports multi-project, multidisciplinary consortia of experts in animal models, molecular biology, immunology, and/or early clinical trials to pursue the refinement/optimization of specific vaccine concepts. Specific activities supported for this initiative include: preclinical development, process optimization, animal modeling, Good Manufacturing Practices, toxicology, product safety testing, regulatory support, and first-in-human investigational clinical studies.

Consortia for AIDS Vaccine Research in Nonhuman Primates

Request for Applications

Contact: Nancy Miller
Phone: 301-435-3753
Email: nmiller@niaid.nih.gov

Objective: The primary focus of the research conducted under this initiative will be to understand the viral and host events that occur at the earliest stages of mucosal infection and how those events can be blocked or modulated by vaccine-induced responses, leading either to prevention of systemic infection or significant reduction in the pathogenic effects of infection. Vaccine candidates may be evaluated for their ability to impact events in early virus infection, not just for their impact on virus load several weeks into the infection. In addition, a secondary objective of this initiative will be to understand the viral and host factors responsible for the nonpathogenic nature of SIV infection in natural-host species.

Description: This initiative will support one or more consortia that address the following four broad areas of fundamental HIV vaccine-related research. Consortia may include core facilities to provide assay support, nonhuman primate (NHP) support, and other resources. Research in any of these areas may include a component designed to optimize a nonhuman primate model to best fit the purposes of the proposed research.

1) Early events of SIV mucosal-route infection.

• Viral and host cellular events during the early period of time when infection is limited to the mucosa at the point of transmission.
• Mucosal innate immune responses to SIV infection and the effect of virus on innate and adaptive immune responses.
• The sequence and kinetics of events that are involved in the spread of virus from localized mucosal sites to draining lymph nodes and to the gut.
• Early events in the gut-associated lymphoid tissue that lead to enhanced virus replication, breakdown of the mucosal barrier, and pathogenic outcome.
• The factors involved in initiating cellular inflammation/activation in acute SIV infection and the factors involved in long-term maintenance of the activation.
• Differences in transmission between distinct mucosal sites.
• Factors responsible for the "bottleneck" in mucosal route infection that lead to establishment of infection by a limited number of virus species.

2) The effect of vaccines on early events in SIV or SHIV mucosal-route infection.

• Characterization and optimization of cellular and humoral immune responses generated by SIV and SHIV vaccines at mucosal sites and evaluation of the effect of those immune responses on virus infection, replication, and spread.
• Understanding the nature of the innate and adaptive immune responses (and their interaction) that can interfere with the establishment and spread of virus infection at mucosal sites or in the gut.
• Determination of whether or not mucosal immunization or mucosal/systemic immunization results in generating better protective immune responses than systemic immunization alone.
• Direct comparison of the ability of different vaccine candidates to induce mucosal immune responses and to protect against mucosal-route virus challenge.

3) Understanding nonpathogenic SIV infection in natural host species.

• The mechanisms underlying the lack of progression to AIDS in natural host species despite initial CD4+ T cell decline and persistent virus replication.
• Direct comparison of responses to acute SIV infection in pathogenic (rhesus or pigtail macaques) versus the nonpathogenic (sooty mangabey, African Green) hosts.
• The mechanisms underlying resistance to mother-to-infant transmission in natural hosts.
• Determination of whether different natural host species have different mechanisms for avoiding the pathogenic effects of SIV infection.

4) Investigation of virus/host interactions in SIV/nonhuman primate models.

• Development of an NHP model that reflects all known aspects of acute HIV infection in humans.
• Development/improvement of aspects of NHP challenge models to provide optimal assessment of vaccine efficacy.