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• W2130132011 endingPage "6368" @default.
• W2130132011 startingPage "6359" @default.
• W2130132011 abstract "ABSTRACT The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing antibody (Ab), 2G12, at a relatively conserved cluster of oligomannose glycans. The discovery of 2G12 raises the possibility that a carbohydrate immunogen may be developed that could elicit 2G12-like neutralizing Abs and contribute to an AIDS vaccine. We have previously dissected the fine specificity of 2G12 and reported that the synthetic tetramannoside (Man 4 ) that corresponds to the D1 arm of Man 9 GlcNAc 2 inhibits 2G12 binding to gp120 as efficiently as Man 9 GlcNAc 2 itself, indicating the potential use of Man 4 as a building block for creating immunogens. Here, we describe the development of neoglycoconjugates displaying variable copy numbers of Man 4 on bovine serum albumin (BSA) molecules by conjugation to Lys residues. The increased valency enhances the apparent affinity of 2G12 for Man 4 up to a limit which is achieved at ∼10 copies per BSA molecule, beyond which no further enhancement is observed. Immunization of rabbits with BSA-(Man 4 ) 14 elicits significant serum Ab titers to Man 4 . However, these Abs are unable to bind gp120. Further analysis reveals that the elicited Abs bind a variety of unbranched and, to a lesser extent, branched Man 9 derivatives but not natural N -linked oligomannose containing the chitobiose core. These results suggest that Abs can be readily elicited against the D1 arm; however, potential differences in the presentation of Man 4 on neoglycoconjugates, compared to glycoproteins, poses challenges for eliciting anti-mannose Abs capable of cross-reacting with gp120 and HIV-1." @default.
• W2130132011 created "2016-06-24" @default.
• W2130132011 creator A5010315360 @default.
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• W2130132011 creator A5056753239 @default.
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• W2130132011 creator A5059815596 @default.
• W2130132011 creator A5062018516 @default.
• W2130132011 creator A5084787730 @default.
• W2130132011 date "2008-07-01" @default.
• W2130132011 modified "2023-10-14" @default.
• W2130132011 title "A Glycoconjugate Antigen Based on the Recognition Motif of a Broadly Neutralizing Human Immunodeficiency Virus Antibody, 2G12, Is Immunogenic but Elicits Antibodies Unable To Bind to the Self Glycans of gp120" @default.
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• W2130132011 doi "https://doi.org/10.1128/jvi.00293-08" @default.
• W2130132011 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2447108" @default.
• W2130132011 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18434393" @default.
• W2130132011 hasPublicationYear "2008" @default.
• W2130132011 type Work @default.

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