Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition.

Published

Journal Article

The N332 high-mannose glycan on the HIV-1 gp120 V3-loop is the target of many bNAbs. About 17% HIV isolates carry the N332 to N334 mutation, but the antibody recognition of the N334 N-glycan and its immunogenicity are not well characterized. Here we report the chemoenzymatic synthesis, antigenicity, and immunogenicity of the V3 N334 glycopeptides from HIV-1 A244 gp120, a key component in the partially successful Thai clinical trials. We found that synthetic V3 glycopeptide carrying a N334 high-mannose glycan could be recognized by bNAb PGT128 and PGT126 but not by 10-1074. Rabbit immunization with the synthetic three-component A244 glycopeptide immunogen elicited substantial glycan-dependent antibodies with broad reactivity to various HIV-1 gp120/gp140 carrying N332 or N334 glycosylation sites. These results indicated that the N334 site is vulnerable and the A244 V3 glycopeptide represents a valuable immunogen for further HIV-1 vaccine studies.

Full Text

Duke Authors

Cited Authors

  • Cai, H; Zhang, R-S; Orwenyo, J; Giddens, J; Yang, Q; LaBranche, CC; Montefiori, DC; Wang, L-X

Published Date

  • November 21, 2018

Published In

Volume / Issue

  • 61 / 22

Start / End Page

  • 10116 - 10125

PubMed ID

  • 30384610

Pubmed Central ID

  • 30384610

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/acs.jmedchem.8b01290

Language

  • eng

Conference Location

  • United States