Concepts represent early planning stages for program announcements, requests for applications, notices of special interest, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.
Note: Council approval does not guarantee that a concept will become an initiative.
Table of Contents
Fiscal Year (FY) 2024 Division of AIDS (DAIDS) Concept
FY 2025 DAIDS Concepts
- Mechanisms of Inducing HIV Immunity in Early Life
- HIV Vaccine Research and Design (HIVRAD) Program
- Virology Core Laboratory
- Humoral Immunology Core Laboratory for AIDS Vaccine Research and Development
- Functional Omics Core Laboratory
- Resource Support Program for AIDS Vaccine Development
- Planning for Product Development Strategy
- Engineering and Preclinical Development of Biological Products that Eliminate HIV-Infected Cells
- Multidisciplinary Research to Accelerate Hepatitis B Cure in Persons Living with HIV and HBV
- Developing a Pipeline of Cell and Gene Therapies for HIV Cure
- Tailoring HIV Curative Strategies to the Individual
For the published notice of special interest, check the June 23, 2023 Guide notice, Notice of Special Interest (NOSI)—HIV Cure-Related Research in Diverse Populations.
Request for Applications—proposed FY 2025 initiative
Objective: The scientific objective of this initiative is to support research to define mechanisms for establishing and maintaining immune responses to HIV in early life (from birth to less than 12 years of age), including impact of pediatric vaccination and broadly neutralizing HIV antibodies to protect against acquisition of HIV infection using human samples and nonhuman primate animal models. The initiative focus is on neonates, infants and pre-adolescents age groups considering that the unique, less preprogrammed immune landscape of early life may present advantages to target HIV prevention strategies for elicitation of anti-HIV immune responses.
Description: This initiative will support basic and translational HIV immunology research to advance mechanistic understanding on how immune ontogeny and functionality in early life could be harnessed in the context of HIV prevention strategies to elicit broad, durable, and protective immunity in children exposed to or unexposed to HIV.
This initiative aims to address the unique immunological and virological challenges of developing an effective HIV vaccine, including an extensive genetic variability of HIV and the limited understanding of immune responses required to protect against HIV acquisition. Key areas of the research focus include 1) evaluation of the pediatric HIV immunization strategies to identify prime innate and adaptive pathways for the development of early and poly-specific broadly neutralizing HIV antibodies lineages, and 2) determination of the biodistribution and efficacy of prophylactic broadly neutralizing antibodies in the evolving pediatric immune landscape.
Additional examples of research interest include, but are not limited to:
- Defining mechanisms for establishing and maintaining immunity to HIV in early life, including active and passive immunization strategies.
- Delineating mechanisms of maternal influence, through breastfeeding, on immune ontogeny and clinical outcomes in the pediatric population including maternal HIV infection status, antiretroviral therapy initiation, broadly neutralizing HIV antibodies treatment, inflammatory milieu, microbiota, and antibodies profile.
- Describing developmental pathways of broadly neutralizing HIV antibodies during pediatric immune maturation.
- Comprehending the mechanisms skewing or exhausting infant immune responses to HIV vaccines and prophylactic broadly neutralizing HIV antibodies in the setting of infectious comorbidities and inflammatory milieu.
- Illustrating longitudinal imaging of pediatric immune cell dynamics and functionality in response to HIV immunization.
- Determining mechanisms of elicitation of tissue specific and mucosal immunity in the context of early life host microbiota and evolving immune landscape.
- Characterizing vaccine adjuvants and immunopotentiators improving pediatric immunity to HIV.
- Understanding molecular regulation of immunity by analyzing multi-omics signatures (e.g., genomics, epigenomics, transcriptomics, proteomics, glycomics, and metabolomics) correlating pediatric immune responses to HIV vaccines and prophylactic broadly neutralizing HIV antibodies.
Clinical trials are not allowed, but use of clinical study samples (birth to less than 12 years of age) is acceptable.
HIV research studies that include animal models may only use nonhuman primates.
For the published program announcement with special receipt, referral, and/or review considerations, check the October 4, 2023 Guide announcement, HIV Vaccine Research and Design (HIVRAD) Program (P01, Clinical Trial Not Allowed).
For the published request for proposals, check the September 7, 2023 solicitation, Virology Core Laboratory.
For the published request for proposals, check the November 17, 2023 solicitation, Humoral Immunology Core Laboratory for AIDS Vaccine Research.
Request for Proposals—proposed FY 2025 initiative
Objective: The scientific objective of this contract initiative is to provide a centralized laboratory to conduct assays that evaluate functional omics approaches in support of preclinical HIV/SIV vaccine studies for the DAIDS contract (Simian Vaccine Evaluation Units) and grant (investigator-initiated research programs) mechanisms, ensuring standardization, consistency, and comparability of data across studies.
Description: The Functional Omics Core Laboratory contract aims to:
- Apply state-of-the-art functional omics approaches to evaluate preclinical HIV/SIV vaccine-elicited immunogenicity and efficacy in nonhuman primate (NHP) challenge/protection studies supported by DAIDS contracts and grant recipients.
- Compile and analyze multi-omics data using appropriate bioinformatics and biocomputing tools to capture the systems-level state of protective immunity and infer drivers of immunity.
- Adopt new and improved technologies and assays.
- Optimize and validate required omics assays and protocols and develop written standard operating procedures to perform genomics, epigenomics, transcriptomics, and proteomics analysis to profile the expression of genes, modifications of DNA/histones, transcripts, and proteins, respectively.
- Compile and maintain an electronic record of all assay results.
- Submit data to a public data repository.
The ultimate goal of the Functional Omics Core Laboratory contract is to identify early omics signatures to evaluate vaccine-induced adaptive and innate immune responses and determine vaccine efficacy in NHP challenge/protection studies supported by DAIDS Simian Vaccine Evaluation Unit contracts and DAIDS grant recipients, promoting standardization and consistency of data across studies.
For the published request for proposals, check the November 1, 2023 solicitation, Resource Support Program for AIDS Vaccine Development.
For the published program announcement with special receipt, referral, and/or review considerations, check the August 15, 2023 Guide announcement, Planning for Product Development Strategy (R34, Clinical Trial Not Allowed).
For the published request for applications, check the October 25, 2023 Guide announcement, Engineering and Preclinical Development of Biological Products that Eliminate HIV-Infected Cells (UG3/UH3, Clinical Trial Not Allowed).
For the published request for applications, check the October 10, 2023 Guide announcement, Multidisciplinary Research to Accelerate Hepatitis B Cure in Persons Living with HIV and HBV (U19, Clinical Trial Not Allowed).
Request for Applications—proposed FY 2025 initiative
Objective: This initiative will enable the development and advancement of gene- and cell-based approaches to achieve long-term remission or elimination of HIV that can eventually be evaluated in the clinic, rendered scalable and deliverable.
Description: The scope of the research includes:
- Novel strategies to target HIV provirus DNA with gene modifying tools to excise, inactivate, or silence the expression of the integrated viral genome.
- Cell- or tissue-targeting methods to enable in vivo delivery of gene therapies to sites where persistent or latent HIV-infected cells reside.
- Allogeneic or universal “off the shelf” cell and gene therapeutic approaches.
- Gene modification to render cells resistant to infection and/or better able to eliminate HIV-infected cells.
- Novel methods to enhance transplantation and engraftment, or minimize rejection, of modified cells.
- Test-of-concept studies in relevant animal models.
Nonresponsive research includes:
- CCR5 as the sole target.
- Transplantation strategies without an HIV component.
- IND-enabling studies, for example Good Laboratory Practices (GLP), pharmacology, and toxicity.
- Applications focused exclusively on HIV infection in the central nervous system.
Note: Clinical trials are not allowed.
Applicants are required to identify one or more private sector partners to participate in their program and to plan an INTERACT (Initial Targeted Engagement for Regulatory Advice on CBER Products https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-interact-meeting) meeting with the FDA within the first 2 years of grant award. These requirements will assist grant recipients in determining the appropriate design and conduct of preclinical test-of-concept studies and the development of their approach.
A Scientific Advisory Board will be established for each grant to assess progress and provide recommendations.
Request for Applications—proposed FY 2025 initiative
Objective: To determine whether tailoring curative strategies to an individual’s specific intact, rebound-competent proviral reservoir and immunologic profile might be more successful than existing, more general approaches at achieving HIV reservoir reduction and/or induction of durable control of viral rebound. The goal is to enable proof-of-concept studies to demonstrate that combination interventions can generate a cure under optimal conditions. This will help guide subsequent prioritization of translational research and optimization of approaches so that they are effective across broader populations of individuals.
Description: This initiative will bring together multidisciplinary teams with expertise in virology, immunology, single-cell analytics, and bioinformatics/modeling to characterize the landscapes of: intact and defective proviruses, host HLA alleles, CD4+ and CD8+ T cell receptor repertoires, and autologous or heterologous neutralizing antibody specificities in virally-suppressed individuals on treatment, and use that information to design combinations of interventions specifically tailored to be effective at targeting and controlling those individuals’ HIV reservoirs.
The scope of research will include basic and preclinical research, methods development and validation, analysis of clinical samples including accessible tissue samples, and testing of combinations of specifically tailored cure strategies in vitro or ex vivo. The focus should be on HIV in humans, but some testing in animal model systems will be permitted if appropriate and well justified. The strategy should be validated across a group of individuals and compared to non-tailored controls to demonstrate rigor, reproducibility, and significance of the results. The curative strategy must combine at least two different immunologic approaches that target an individual’s proviral reservoir sequences – for example, combining adaptive cellular responses with humoral HIV-gene-specific targeted approaches. Non-immunologic tailored approaches, such as gene editing of provirus or CCR5, LTR targeting, or block-and-lock strategies will not be responsive. The research plan should also include a tailored strategy for reactivation of reservoir cells – for example, targeting based on the antigenic specificity of the reservoir cells.
Clinical trials are not allowed, but use of blood and tissue samples from clinical trials funded through separate mechanisms will be encouraged. The proposal should take into account the requirements for downstream implementation of the tailored approach in future clinical trials, such as discussion of regulatory requirements for interventions and diagnostic assays and how GMP materials would be produced.