Synthetic Three-Component HIV-1 V3 Glycopeptide Immunogens Induce Glycan-Dependent Antibody Responses.

Published

Journal Article

Eliciting broadly neutralizing antibody (bNAb) responses against HIV-1 is a major goal for a prophylactic HIV-1 vaccine. One approach is to design immunogens based on known broadly neutralizing epitopes. Here we report the design and synthesis of an HIV-1 glycopeptide immunogen derived from the V3 domain. We performed glycopeptide epitope mapping to determine the minimal glycopeptide sequence as the epitope of V3-glycan-specific bNAbs PGT128 and 10-1074. We further constructed a self-adjuvant three-component immunogen that consists of a 33-mer V3 glycopeptide epitope, a universal T helper epitope P30, and a lipopeptide (Pam3CSK4) that serves as a ligand of Toll-like receptor 2. Rabbit immunization revealed that the synthetic self-adjuvant glycopeptide could elicit substantial glycan-dependent antibodies that exhibited broader recognition of HIV-1 gp120s than the non-glycosylated V3 peptide. These results suggest that the self-adjuvant synthetic glycopeptides can serve as an important component to elicit glycan-specific antibodies in HIV vaccine design.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • December 2017

Published In

Volume / Issue

  • 24 / 12

Start / End Page

  • 1513 - 1522.e4

PubMed ID

  • 29107699

Pubmed Central ID

  • 29107699

Electronic International Standard Serial Number (EISSN)

  • 2451-9448

International Standard Serial Number (ISSN)

  • 2451-9456

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2017.09.005

Language

  • eng