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Advancing HIV Vaccine Development with a Lipid Nanodisc Platform

Award Number: R01AI192143
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: 02/13/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Advancing HIV Vaccine Development with a Lipid Nanodisc Platform - Project Summary The envelope (Env) glycoprotein of HIV is the only viral protein on the surface of virions, making it the sole target of B cell-based HIV vaccines. While Env is natively a transmembrane protein, most vaccine development relies on soluble versions of the trimer. These versions lack the membrane-proximal external region (MPER) epitope, the native bilayer environment, and the transmembrane (TM) and C- terminal (CT) domains. Broadly neutralizing antibodies (bnAbs) targeting MPER have remarkable breadth, reaching near-complete coverage of all circulating HIV strains, thus making MPER an attractive target for vaccine development. Recent progress in MPER-targeted vaccine development has been notable on two fronts. First, in the HVTN133 clinical trial, MPER peptide presented in a liposome formulation induced a B cell lineage for bnAbs and their precursors and reached 15 % neutralization breadth of a global tier 2 panel. Second, two studies described the development of a germline targeting immunogen for 10E8-class MPER bnAb, and affinity maturation process of the primed antibodies in pre-clinical mouse models. Characterization of new and improved MPER- targeting immunogen candidates and responses they elicit will require biophysical and structural analysis. Challenges in handling Env as a recombinant transmembrane protein therefore persist. This project incorporates engineered transmembrane Env vaccine candidates into stable lipid nanodiscs using membrane scaffold proteins and a selection of lipid molecules. This solution enables scalable and reproducible in vitro characterization and optimization of engineered transmembrane Env-based immunogens and evaluation of in vivo responses from MPER-targeting immunizations. Env nanodiscs allow using transmembrane Envs under identical conditions that have been established for soluble Envs in commonly used iterative vaccine development methods. In the first specific aim of this proposal, Env nanodisc structures are solved in complex with MPER-targeting antibodies to give guideposts for vaccine development. In the second, nanodiscs are assembled with controlled lipid compositions to elucidate the contribution of the bilayer surface to MPER antibody binding. Lastly, the third specific aim establishes conditions for utilizing Env nanodiscs in electron microscopy- based polyclonal epitope mapping (EMPEM). All aims will collectively contribute to improved nanodisc assembly pipeline that can be scaled to serve multiple HIV MPER targeting vaccine development projects. This pipeline can also serve the development of any transmembrane Env immunogen that targets other epitopes. Ultimately, the tools will be made available for other virus glycoprotein vaccine development projects beyond HIV.


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 = $511,531 )
2026	2026	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/13/2026	NEW	$511,531
														Subtotal = $511,531

Grand Total All Awards = $511,531

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Advancing HIV Vaccine Development with a Lipid Nanodisc Platform

Award Number: R01AI192143

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: 02/13/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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