Gold Nanoparticles Coated with Oligomannosides of HIV-1 Glycoprotein gp120 Mimic the Carbohydrate Epitope of Antibody 2G12

After three decades of research, an effective vaccine against the pandemic AIDS caused by human immunodeficiency virus (HIV) is not still available, and a deeper understanding of HIV immunology, as well as new chemical tools that may contribute to improve the currently available arsenal against the virus, is highly wanted. Among the few broadly neutralizing human immunodeficiency virus type 1 (HIV-1) monoclonal antibodies, 2G12 is the only carbohydrate-directed one. 2G12 recognizes a cluster of high-mannose glycans on the viral envelope glycoprotein gp120. This type of glycan has thus been envisaged as a target to develop an HIV vaccine that is capable of eliciting 2G12-like antibodies. Herein we show that gold nanoparticles coated with self-assembled monolayers of synthetic oligomannosides [manno-gold glyconanoparticles (GNPs)], which are present in gp120, are able to bind 2G12 with high affinity and to interfere with 2G12/gp120 binding, as determined by surface plasmon resonance and saturation transfer difference NMR spectroscopy. Cellular neutralization assays demonstrated that GNPs coated with a linear tetramannoside could block the 2G12-mediated neutralization of a replication-competent virus under conditions that resemble the ones in which normal serum prevents infection of the target cell. Dispersibility in water and physiological media, absence of cytotoxicity, and the possibility of inserting more than one component into the same nanoparticle make manno-GNPs versatile, polyvalent, and multifunctional systems that may aid efforts to develop new multifaceted strategies against HIV.

Graphical AbstractFigure optionsDownload high-quality image (120 K)Download as PowerPoint slideResearch Highlights
► This study used gold nanoparticles coated with oligomannosides (manno-GNPs) as antibody 2G12 ligands.
► manno-GNPs display oligomannosides of HIV-1 glycoprotein gp120 in a multivalent way.
► manno-GNPs bind 2G12 and inhibit 2G12/gp120 interaction, as measured by surface plasmon resonance.
► In NMR titrations, manno-GNPs displace oligomannosides from 2G12 binding sites.
► In cellular assays, selected manno-GNPs block the 2G12 neutralization of HIV-1.