biostudies-literatureD'Addabbo ANational Institutes of HealthIAVI Neutralizing Antibody Center through the Collaboration for AIDS Vaccine DiscoveryNIH HHScwae063https://www.ebi.ac.uk/biostudies/studies/S-EPMC11442005biostudies-literatureUnknown34(11)Broadly neutralizing antibodies (bNAbs) isolated from HIV-1 infected donors are vaccine paradigms. These bNAbs recognize envelope glycoprotein trimers that carry 75-90 oligomannose and complex-type glycans. Although bNAbs and their precursors must navigate past glycans, they usually also make some glycan contacts. Glycan-modified vaccines may therefore be useful to initiate and guide bNAb development. Here, we describe two ways to modify Env glycans for possible vaccine use: 1) using a cocktail of glycosidases (termed "NGAF3" (Neuraminidase, β-Galactosidase, N-Acetylglucosaminidase, endoglycosidase F3 (endo F3)) to deplete complex glycans to try to minimize bNAb-glycan clashes and 2) co-expressing β-1,4-galactosyltransferase 1 (B4G) and β-galactoside α-2,6 sialyltransferase 1 (ST6) during GlycobiologyImpact of glycan depletion, glycan debranching and increased glycan charge on HIV-1 neutralization sensitivity and immunogenicity.PMC11442005AI93278AI00790OPP1153692/INV-008813D'Addabbo ABinley JMThomas AOsawa KAllen JDCrooks ETTong TXu JCrispin MfalseImpact of glycan depletion, glycan debranching and increased glycan charge on HIV-1 neutralization sensitivity and immunogenicity.Broadly neutralizing antibodies (bNAbs) isolated from HIV-1 infected donors are vaccine paradigms. These bNAbs recognize envelope glycoprotein trimers that carry 75-90 oligomannose and complex-type glycans. Although bNAbs and their precursors must navigate past glycans, they usually also make some glycan contacts. Glycan-modified vaccines may therefore be useful to initiate and guide bNAb development. Here, we describe two ways to modify Env glycans for possible vaccine use: 1) using a cocktail of glycosidases (termed "NGAF3" (Neuraminidase, β-Galactosidase, N-Acetylglucosaminidase, endoglycosidase F3 (endo F3)) to deplete complex glycans to try to minimize bNAb-glycan clashes and 2) co-expressing β-1,4-galactosyltransferase 1 (B4G) and β-galactoside α-2,6 sialyltransferase 1 (ST6) during 2024-01-01T00:00:00Z2024 Sep2026-04-07T13:24:05.612Z2026-04-07T13:21:09.669ZS-EPMC114420053911536110.1093/glycob/cwae063