7L85

Designed tetrahedral nanoparticle T33-31 presenting BG505 SOSIP trimers

7L85 の概要

• エントリーDOI: 10.2210/pdb7l85/pdb
• EMDBエントリー: 23222
• 分子名称: BG505 SOSIP-T33-31B, BG505 SOSIP-T33-31A (2 entities in total)
• 機能のキーワード: hiv, vaccine design, protein design, nanoparticles, bg505, viral protein, de novo protein
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 304537.52

構造登録者

Antanasijevic, A.,Sewall, L.M.,Ward, A.B. (登録日: 2020-12-31, 公開日: 2021-08-04, 最終更新日: 2024-05-29)

主引用文献

Antanasijevic, A.,Sewall, L.M.,Cottrell, C.A.,Carnathan, D.G.,Jimenez, L.E.,Ngo, J.T.,Silverman, J.B.,Groschel, B.,Georgeson, E.,Bhiman, J.,Bastidas, R.,LaBranche, C.,Allen, J.D.,Copps, J.,Perrett, H.R.,Rantalainen, K.,Cannac, F.,Yang, Y.R.,de la Pena, A.T.,Rocha, R.F.,Berndsen, Z.T.,Baker, D.,King, N.P.,Sanders, R.W.,Moore, J.P.,Crotty, S.,Crispin, M.,Montefiori, D.C.,Burton, D.R.,Schief, W.R.,Silvestri, G.,Ward, A.B.
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
Nat Commun, 12:4817-4817, 2021

PubMed Abstract: Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.

PubMed: 34376662
DOI: 10.1038/s41467-021-25087-4

実験手法

ELECTRON MICROSCOPY (2.9 Å)