Thursday, January 1, 2026 1/1/2026

Lymph node targeting nanoparticles for HIV Env proteins

Award Number: R21AI167690
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: 08/10/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Lymph node targeting nanoparticles for HIV Env proteins - PROJECT SUMMARY With the advent of highly successful antiretroviral therapy, mortality and morbidity associated with human immunodeficiency virus (HIV) infection has been significantly reduced. Despite this, hundreds of thousands of new HIV infections occur each year, demonstrating the need for a safe and effective vaccine. HIV vaccines based on the elicitation of broadly neutralizing antibodies (bNAbs) are at the forefront of HIV research. Stabilized HIV immunogens have now shown the ability to elicit tier 2 neutralizing antibodies in rhesus macaques, and numerous bNAbs have been isolated from human subjects. Furthermore, germline targeting immunogens have demonstrated initial success in humans in eliciting bNAb germline precursors. A key aspect in the effectiveness of HIV immunogens is the delivery method. Somatic hypermutation is a critical event for optimal and efficient bNAb elicitation. Recombinant HIV Env proteins are poorly immunogenic and fail to follow typical lymph node (LN) trafficking pathways due to high glycosylation and poor recognition by natural IgM. Instead, recombinant HIV Env proteins are captured by interfollicular macrophages rather than by macrophages in the subcapsular sinus, leading to poor antigen availability and limited repeated somatic hypermutation. The scientific premise for this proposal is that since recombinant HIV Env proteins have altered LN trafficking, biodegradable LN targeting nanoparticles that facilitate transfer of soluble HIV Env trimers directly to LNs are a promising tool to circumvent current barriers. Our objective is to test the hypothesis that a lymph node (LN) targeting nanoparticle (NP) technology will improve immune responses generated by human immunodeficiency virus (HIV) envelope (Env) protein immunogens. This proposal is high risk, as the elicitation of broadly neutralizing antibodies (bNAbs) at a high titer and long duration is challenging; nonetheless, if successful, it offers high reward by substantially improving HIV Env vaccine responses. In Specific Aim 1, we will determine if PLGA-b-PEG NPs more efficiently deliver germline targeting immunogens to LN follicles and increase somatic hypermutation compared to unencapsulated immunogens. Mice will be immunized with germline targeting immunogen trimers encapsulated within the NP platform, and serological and cellular analysis will be completed, including monitoring of somatic hypermutation using single cell sequencing approaches. LN trafficking and accumulation in follicles will also be assessed. In Specific Aim 2, we will determine if co-encapsulation of diverse HIV Envs in NPs enhances elicitation of tier 2 neutralization breadth. HIV Env SOSIP trimers from two viral clades will be combined in a single NP, and serological responses will be assessed. This proposal is highly collaborative, combining Dr. Jarrod Mousa, a structural immunologist and HIV/AIDS Vaccine Scholars Program recipient, and Dr. Hai-Quan Mao, a biomaterials and nanomedicine expert. Our findings have high potential to dramatically improve HIV Env responses, and our findings will be applicable to the entire HIV vaccine field.


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 = $0 )
2026	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	000	3	12/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = -$5,172 )
2025	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	2	1/21/2025	NON-COMPETING CONTINUATION	-$5,172
2025	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	1/21/2025	NEW	-$5,172
2025	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	002	3	1/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$42,356
2025	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	1/21/2025	NEW	-$37,184
														Subtotal = -$5,172

Issue Date FY: 2024 ( Subtotal = $33,425 )
2024	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	4/17/2024	NON-COMPETING CONTINUATION	-$188,423
2024	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	001	3	4/17/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$221,848
														Subtotal = $33,425

Issue Date FY: 2023 ( Subtotal = $193,595 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	6/22/2023	NON-COMPETING CONTINUATION	$193,595
														Subtotal = $193,595

Issue Date FY: 2022 ( Subtotal = $246,900 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	8/10/2022	NEW	$246,900
														Subtotal = $246,900

Grand Total All Awards = $468,748

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Lymph node targeting nanoparticles for HIV Env proteins

Award Number: R21AI167690

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: 08/10/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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