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Nanotrap Therapeutic Vaccines for HIV Virion Capture and Infected Cell Targeting

Award Number: R01AI203404
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Nanotrap Therapeutic Vaccines for HIV Virion Capture and Infected Cell Targeting - Project Summary: Therapeutic vaccination for HIV remains an unsolved challenge due to HIV’s extreme genetic diversity, glycan masking of Env, and early establishment of viral reservoirs. Most therapeutic vaccines fail because their antigens do not match the patient’s autologous virus, resulting in weak or non-protective immune responses. To overcome this limitation, we developed nanotrap therapeutic vaccines (NTVs)—engineered liposomal nanoparticles that display multivalent CD4 mimetic (CD4m) ligands to capture circulating HIV and encapsulate innate immune agonists that are delivered specifically to antigen-presenting cells (APCs) during virion uptake. NTVs transform the patient’s own virus into an autologous immunogen, eliminating the need for viral sequence prediction. Preliminary studies demonstrated that NTVs efficiently bind HIV virions, promote APC uptake, and induce strong antiviral CD8 T-cell responses in vivo. We also observed that NTVs bind gp120 expressed on infected cells, suggesting a synergistic mechanism in which NTVs activate and expose infected cells for immune clearance while simultaneously amplifying virion release for further capture. This R01 will define the molecular and immunological design rules governing NTV activity. Aim 1 will determine how NTV–virion complex size and biophysical properties influence APC uptake and downstream immunity. Aim 2 will evaluate how NTV-delivered innate agonists regulate APC activation states and therapeutic CD8 T-cell priming. Aim 3 will characterize NTV interactions with infected cells and identify mechanisms by which NTVs enhance viral antigen visibility and promote immune-mediated clearance. Successful completion of this project will establish a mechanistically grounded therapeutic vaccine platform and identify a preclinical NTV candidate suitable for advancement into non-human primate testing. These studies address key obstacles in therapeutic HIV vaccine development and may ultimately reduce the need for lifelong ART.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $624,806 )
2026	2026	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	9/1/2026	NEW	$624,806
														Subtotal = $624,806

Grand Total All Awards = $624,806

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Nanotrap Therapeutic Vaccines for HIV Virion Capture and Infected Cell Targeting

Award Number: R01AI203404

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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