Isolation and Structure of an Antibody that Fully Neutralizes Isolate SIVmac239 Reveals Functional Similarity of SIV and HIV Glycan Shields.

Published

Journal Article

HIV- and SIV-envelope (Env) trimers are both extensively glycosylated, and antibodies identified to date have been unable to fully neutralize SIVmac239. Here, we report the isolation, structure, and glycan interactions of antibody ITS90.03, a monoclonal antibody that completely neutralized the highly neutralization-resistant isolate, SIVmac239. The co-crystal structure of a fully glycosylated SIVmac239-gp120 core in complex with rhesus CD4 and the antigen-binding fragment of ITS90.03 at 2.5-Å resolution revealed that ITS90 recognized an epitope comprised of 45% glycan. SIV-gp120 core, rhesus CD4, and their complex could each be aligned structurally to their human counterparts. The structure revealed that glycans masked most of the SIV Env protein surface, with ITS90 targeting a glycan hole, which is occupied in ∼83% of SIV strains by glycan N238. Overall, the SIV glycan shield appears to functionally resemble its HIV counterpart in coverage of spike, shielding from antibody, and modulation of receptor accessibility.

Full Text

Duke Authors

Cited Authors

  • Gorman, J; Mason, RD; Nettey, L; Cavett, N; Chuang, G-Y; Peng, D; Tsybovsky, Y; Verardi, R; Nguyen, R; Ambrozak, D; Biris, K; LaBranche, CC; Ramesh, A; Schramm, CA; Zhou, J; Bailer, RT; Kepler, TB; Montefiori, DC; Shapiro, L; Douek, DC; Mascola, JR; Roederer, M; Kwong, PD

Published Date

  • October 15, 2019

Published In

Volume / Issue

  • 51 / 4

Start / End Page

  • 724 - 734.e4

PubMed ID

  • 31586542

Pubmed Central ID

  • 31586542

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2019.09.007

Language

  • eng

Conference Location

  • United States