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Evaluation of HIV-1 Env-C3d constructs on nanoparticles for structure, function and immunogenicity.

Award Number: R21AI203583
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: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Evaluation of HIV-1 Env-C3d constructs on nanoparticles for structure, function and immunogenicity. - SUMMARY A broadly effective HIV-1 vaccine remains a high priority to eliminate the spread of this highly pathogenic virus in the human population. Broadly neutralizing antibodies (bNAbs) against the viral envelope (Env) trimeric spike are induced in a small population of infected people primarily owing to continuous activation of the immune system by the replicating virus to fine tune antibody responses to multiple sites of vulnerability on Env trimer. Elicitation of such bNAbs by vaccination is highly challenging and would probably need a series of candidate vaccine immunogens that effectively prime and boost to achieve neutralization breadth. Recently, we have elicited broadly cross-reactive serum and serum IgG responses in multiple macaques immunized with a series of recombinant highly stable and homogeneous Env NFL trimers either as soluble trimers or arrayed at high- density on the surface of stable covalent trimer-liposomes. The antibodies from these studies targeted the gp120:gp120 domain interface encompassing the highly conserved CD4 binding site (CD4bs) and the trimer apex respectively. We previously designed Env fused with one copy of molecular adjuvant C3d to further improve the immunogenicity in vivo. We will evaluate Env-C3d candidates with two and three copies of C3d domains per gp160 subunit (+/- Fc domain) in C57BL/6 and Alloy mice for germinal center formation, antigen retention, longevity, cross-neutralizing antibodies, responder frequency and epitope targeting. Analysis and evaluation of the Env-C3d fusion candidates both in vitro and in vivo will have broader implications in vaccine design for multiple pathogens.


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 = $276,000 )
2026	2026	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	7/1/2026	NEW	$276,000
														Subtotal = $276,000

Grand Total All Awards = $276,000

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Evaluation of HIV-1 Env-C3d constructs on nanoparticles for structure, function and immunogenicity.

Award Number: R21AI203583

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: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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