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Assessing the impact of HIV-Env inter-clade glycoform conservation on broadly neutralizing antibody recognition

Award Number: F32AI195008
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Assessing the impact of HIV-Env inter-clade glycoform conservation on broadly neutralizing antibody recognition - PROJECT SUMMARY/ABSTRACT Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS), a global health crisis that continues to affect millions. As of the end of 2023, approximately 40 million people are living with HIV (PLWH), with over 1 million new infections reported annually. Despite significant advancements in antiretroviral therapy (ART) that effectively manage HIV infection, no cure or broadly effective vaccine exists. The development of an HIV vaccine capable of eliciting a robust and broadly protective immune response remains a critical unmet need. The envelope glycoprotein (Env), the sole antigenic target of HIV, is densely shielded by a complex array of N-linked glycans that obscure conserved peptide epitopes from host immune surveillance. While broadly neutralizing antibodies (bnAbs) have demonstrated the ability to engage glycans at their binding sites, the impact of glycan distribution and heterogeneity across different HIV subtypes on bnAb binding is poorly understood. I hypothesize that the conservation of glycoforms across HIV clades is a key determinant of bnAb binding breadth and neutralization and represents a crucial consideration for designing vaccine antigens targeting conserved regions of Env. To address this hypothesis, I propose two aims. First, I will establish a standardized and scalable glycan similarity network to confidently map glycoform conservation across HIV clades. This network will leverage advanced glycoproteomics techniques, including a novel statistical framework designed to ensure rigorous dataset comparison and high data quality. By integrating these tools, I aim to identify conserved glycan motifs contributing to bnAb binding breadth. Second, I will employ glycoengineering and modeling approaches to experimentally assess the functional role of glycoform conservation in bnAb binding and neutralization. Specifically, I will manipulate glycoform distributions of HIV-Env glycoproteins to mimic those of other subtypes and assess the impact on bnAb binding using biolayer interferometry. Glycoengineering strategies will include molecular modeling, engineered cell lines, exogenous glycosidases and glycosyltransferases, and site-directed mutagenesis to achieve precise control over N- glycosylation patterns globally and at specific sites. The findings from this research will advance our understanding of the structural and functional determinants of bnAb binding and provide critical insights into the role of glycan heterogeneity in immune recognition. These results will inform the rational design of novel HIV- Env antigens for vaccine development and have broader implications for glycoimmunology, including applications to other glycan-shielded viral glycoproteins and cancer-associated glycoproteins.


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 = $76,780 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	5/12/2026	NEW	$76,780
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	1	5/12/2026	NEW	$0
														Subtotal = $76,780

Grand Total All Awards = $76,780

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Assessing the impact of HIV-Env inter-clade glycoform conservation on broadly neutralizing antibody recognition

Award Number: F32AI195008

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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