Unprecedented Role of Hybrid N-Glycans as Ligands for HIV-1 Broadly Neutralizing Antibodies

• DOI: 10.1021/jacs.8b00896
• Publication Date: 2018-03-26T16:54:04Z
• Authors: Vidya S. Shivatare; Sachin S. Shivatare; Chang-Chun David Lee; Chi-Hui Liang; Kuo-Shiang Liao; Yang-Yu Cheng; Gannerla Saidachary; Chung-Yi Wu; Nan-Horng Lin; Peter D. Kwong; Dennis R. Burton; Chung-Yi Wu; Chi-Huey Wong
• Keywords: Avidity

The development of an HIV vaccine has been hampered by the extraordinary mutability and genetic diversity virus, particularly substantial sequence gp120 gp 41 envelope glycoproteins existing in more than 2000 variants. highly diverse glycans on spikes are commonly considered as immunologically silent self-antigens; however, discovery potent broadly neutralizing antibodies (bNAbs) from patients targeting viral surface raised a major question about origin their antigens. Recent epitope mapping studies bNAb PG9 indicated requirement properly spaced high mannose complex type glycan connected short peptide spacer. We have recently discovered that 1:1 mixture Man5 sialyl biantennary with well-defined distance without spacer is well recognized avidity and, thus, proposed hybrid oligomannose complex-type arm could be proper ligand PG9. To verify this proposition, we first designed chemo-enzymatically synthesized series unusual hybrid-type N-glycan structures, which may exist through host-guided N-glycosylation pathway. synthetic were then used to prepare arrays for binding several other bNAbs, including PG16, PGT121, PGT128-3C, 2G12, VRC13, VRC-PG05, VRC26.25, VRC26.09, PGDM1400, 35O22, 10-1074. Our results demonstrated some bNAbs bind strong (subnanomolar Kd) certain suggesting these serve epitopes design vaccines against HIV.