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• W2109562998 abstract "ABSTRACT Experimental vaccine antigens based upon the HIV-1 envelope glycoproteins (Env) have failed to induce neutralizing antibodies (NAbs) against the majority of circulating viral strains as a result of antibody evasion mechanisms, including amino acid variability and conformational instability. A potential vaccine design strategy is to stabilize Env, thereby focusing antibody responses on constitutively exposed, conserved surfaces, such as the CD4 binding site (CD4bs). Here, we show that a largely trimeric form of soluble Env can be stably cross-linked with glutaraldehyde (GLA) without global modification of antigenicity. Cross-linking largely conserved binding of all potent broadly neutralizing antibodies (bNAbs) tested, including CD4bs-specific VRC01 and HJ16, but reduced binding of several non- or weakly neutralizing antibodies and soluble CD4 (sCD4). Adjuvanted administration of cross-linked or unmodified gp140 to rabbits generated indistinguishable total gp140-specific serum IgG binding titers. However, sera from animals receiving cross-linked gp140 showed significantly increased CD4bs-specific antibody binding compared to animals receiving unmodified gp140. Moreover, peptide mapping of sera from animals receiving cross-linked gp140 revealed increased binding to gp120 C1 and V1V2 regions. Finally, neutralization titers were significantly elevated in sera from animals receiving cross-linked gp140 rather than unmodified gp140. We conclude that cross-linking favors antigen stability, imparts antigenic modifications that selectively refocus antibody specificity and improves induction of NAbs, and might be a useful strategy for future vaccine design." @default.
• W2109562998 created "2016-06-24" @default.
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• W2109562998 date "2013-09-15" @default.
• W2109562998 modified "2023-10-12" @default.
• W2109562998 title "Immune Focusing and Enhanced Neutralization Induced by HIV-1 gp140 Chemical Cross-Linking" @default.
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• W2109562998 doi "https://doi.org/10.1128/jvi.01161-13" @default.
• W2109562998 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3754013" @default.
• W2109562998 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23843636" @default.
• W2109562998 hasPublicationYear "2013" @default.
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