This grant aims to advance strategies for eliminating HIV-1 latent reservoirs, particularly those in the Central Nervous System (CNS), where current ‘shock and kill’ approaches face unique challenges. While latency reactivating agents have shown limitations, this initiative focuses on optimizing reservoir cell recognition and elimination using novel immunotherapy and gene editing techniques. Immunotherapy approaches include therapeutic vaccines, CAR-T cells, broadly neutralizing antibodies, dual-affinity retargeting antibodies, and immune modulators to enhance immune response. Gene editing utilizes tools like TALEN or CRISPR/Cas9 to excise the provirus. A critical aspect is overcoming the blood-brain barrier for CNS access and thoroughly assessing the potential CNS toxicity of these advanced eradication strategies, which are predominantly studied in peripheral reservoirs.
Opportunity ID: 333755
General Information
| Document Type: | Grants Notice |
| Funding Opportunity Number: | RFA-MH-21-225 |
| Funding Opportunity Title: | Adapting Immunotherapy and Gene Editing Based Strategies for Targeting HIV Reservoirs in the CNS: Potential Benefits and Risks (R01 Clinical Trial Optional) |
| Opportunity Category: | Discretionary |
| Opportunity Category Explanation: | – |
| Funding Instrument Type: | Grant |
| Category of Funding Activity: | Health |
| Category Explanation: | – |
| Expected Number of Awards: | – |
| Assistance Listings: | 93.242 — Mental Health Research Grants |
| Cost Sharing or Matching Requirement: | No |
| Version: | Synopsis 1 |
| Posted Date: | May 24, 2021 |
| Last Updated Date: | May 24, 2021 |
| Original Closing Date for Applications: | Aug 27, 2021 |
| Current Closing Date for Applications: | Aug 27, 2021 |
| Archive Date: | Oct 02, 2021 |
| Estimated Total Program Funding: | – |
| Award Ceiling: | – |
| Award Floor: | – |
Eligibility
| Eligible Applicants: | Small businesses County governments Special district governments State governments Independent school districts Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Public housing authorities/Indian housing authorities Public and State controlled institutions of higher education City or township governments Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education For profit organizations other than small businesses Private institutions of higher education Others (see text field entitled “Additional Information on Eligibility” for clarification) Native American tribal organizations (other than Federally recognized tribal governments) Native American tribal governments (Federally recognized) |
| Additional Information on Eligibility: | Other Eligible Applicants include the following: Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Eligible Agencies of the Federal Government; Faith-based or Community-based Organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (Other than Federally Recognized); Non-domestic (non-U.S.) Entities (Foreign Organizations); Regional Organizations; Tribally Controlled Colleges and Universities (TCCUs) ; U.S. Territory or Possession. |
Additional Information
| Agency Name: | National Institutes of Health |
| Description: | The shock and kill strategy is one of the commonly used approaches for targeting latent reservoirs in hopes to cure HIV-1. It is based on the concept of purposely inducing reactivation of latent reservoirs in ART (antiretroviral therapy)-treated individuals by using stimulatory agents. However, it has become increasingly evident that attempts at elimination of HIV-1 reservoirs through latency reactivating agents (LRA) -mediated reactivation alone may not be sufficient. Novel strategies such as immunotherapy and gene excision therapies to optimize the recognition and elimination of reservoir cells such are being conceptualized and researched. Immunotherapy strategies like therapeutic vaccines to enhance HIV-1-specific CTL (cytotoxic T-cell) response, Chimeric Antigen Receptor T-cells (CAR-T cells) therapies, broadly neutralizing antibodies, dual-affinity retargeting antibodies that not only bind to HIV-1 viral envelope antigen but also activate the CTL response, and immune modulators, such as anti-PD1 (programmed cell death protein-1) or anti-CTL4 antibodies, to correct the immune exhaustion noticed in ART-treated individuals are being developed. In addition to immunotherapy strategies, Recombinant TALEN or CRISPR/Cas9 gene editing molecules delivered to latently infected cells designed to induce cleavage at highly conserved regions of the integrated HIV provirus genome are being researched. However, majority of immunotherapy-based and gene editing based HIV eradication strategies are focused on the periphery. The brain presents a unique challenge where access is difficult and innovative strategies are needed to overcome the blood brain barrier. It is also important to understand the potential CNS toxicity of immunotherapy-based and gene-editing based approaches currently being tested in clinical trials |
| Link to Additional Information: | http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-21-225.html |
| Grantor Contact Information: | If you have difficulty accessing the full announcement electronically, please contact:
NIH OER Webmaster
grantsinfo@nih.gov Email:grantsinfo@nih.gov |
Version History
| Version | Modification Description | Updated Date |
|---|---|---|
Related Documents
There are no related documents on this grant.
Packages
| Agency Contact Information: | NIH OER Webmaster grantsinfo@nih.gov Email: grantsinfo@nih.gov |
| Who Can Apply: | Organization Applicants |
| Assistance Listing Number | Competition ID | Competition Title | Opportunity Package ID | Opening Date | Closing Date | Actions |
|---|---|---|---|---|---|---|
| FORMS-F | Use for due dates on or after May 25, 2020 | PKG00267349 | Jul 27, 2021 | Aug 27, 2021 | View |
Package 1
Mandatory forms
333755 RR_SF424_2_0-2.0.pdf
333755 PHS398_CoverPageSupplement_5_0-5.0.pdf
333755 RR_OtherProjectInfo_1_4-1.4.pdf
333755 PerformanceSite_2_0-2.0.pdf
333755 RR_KeyPersonExpanded_2_0-2.0.pdf
333755 PHS398_ResearchPlan_4_0-4.0.pdf
333755 PHSHumanSubjectsAndClinicalTrialsInfo_2_0-2.0.pdf
Optional forms
333755 RR_Budget_1_4-1.4.pdf
333755 RR_SubawardBudget30_1_4-1.4.pdf
333755 PHS398_ModularBudget_1_2-1.2.pdf
333755 PHS_AssignmentRequestForm_3_0-3.0.pdf
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