Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.

Published

Journal Article

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

Full Text

Duke Authors

Cited Authors

  • Zhou, T; Doria-Rose, NA; Cheng, C; Stewart-Jones, GBE; Chuang, G-Y; Chambers, M; Druz, A; Geng, H; McKee, K; Kwon, YD; O'Dell, S; Sastry, M; Schmidt, SD; Xu, K; Chen, L; Chen, RE; Louder, MK; Pancera, M; Wanninger, TG; Zhang, B; Zheng, A; Farney, SK; Foulds, KE; Georgiev, IS; Joyce, MG; Lemmin, T; Narpala, S; Rawi, R; Soto, C; Todd, J-P; Shen, C-H; Tsybovsky, Y; Yang, Y; Zhao, P; Haynes, BF; Stamatatos, L; Tiemeyer, M; Wells, L; Scorpio, DG; Shapiro, L; McDermott, AB; Mascola, JR; Kwong, PD

Published Date

  • April 25, 2017

Published In

Volume / Issue

  • 19 / 4

Start / End Page

  • 719 - 732

PubMed ID

  • 28445724

Pubmed Central ID

  • 28445724

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.04.013

Language

  • eng

Conference Location

  • United States