Oligomannose Glycopeptide Conjugates Elicit Antibodies Targeting the Glycan Core Rather than Its Extremities.

Published

Journal Article

Up to ∼20% of HIV-infected individuals eventually develop broadly neutralizing antibodies (bnAbs), and many of these antibodies (∼40%) target a region of dense high-mannose glycosylation on gp120 of the HIV envelope protein, known as the "high-mannose patch" (HMP). Thus, there have been numerous attempts to develop glycoconjugate vaccine immunogens that structurally mimic the HMP and might elicit bnAbs targeting this conserved neutralization epitope. Herein, we report on the immunogenicity of glycopeptides, designed by in vitro selection, that bind tightly to anti-HMP antibody 2G12. By analyzing the fine carbohydrate specificity of rabbit antibodies elicited by these immunogens, we found that they differ from some natural human bnAbs, such as 2G12 and PGT128, in that they bind primarily to the core structures within the glycan, rather than to the Manα1 → 2Man termini (2G12) or to the whole glycan (PGT128). Antibody specificity for the glycan core may result from extensive serum mannosidase trimming of the immunogen in the vaccinated animals. This finding has broad implications for vaccine design aiming to target glycan-dependent HIV neutralizing antibodies.

Full Text

Duke Authors

Cited Authors

  • Nguyen, DN; Xu, B; Stanfield, RL; Bailey, JK; Horiya, S; Temme, JS; Leon, DR; LaBranche, CC; Montefiori, DC; Costello, CE; Wilson, IA; Krauss, IJ

Published Date

  • February 27, 2019

Published In

Volume / Issue

  • 5 / 2

Start / End Page

  • 237 - 249

PubMed ID

  • 30834312

Pubmed Central ID

  • 30834312

International Standard Serial Number (ISSN)

  • 2374-7943

Digital Object Identifier (DOI)

  • 10.1021/acscentsci.8b00588

Language

  • eng

Conference Location

  • United States