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-Structure paper
| タイトル | Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 4817, Year 2021 |
| 掲載日 | 2021年8月10日 |
 著者 | Aleksandar Antanasijevic / Leigh M Sewall / Christopher A Cottrell / Diane G Carnathan / Luis E Jimenez / Julia T Ngo / Jennifer B Silverman / Bettina Groschel / Erik Georgeson / Jinal Bhiman / Raiza Bastidas / Celia LaBranche / Joel D Allen / Jeffrey Copps / Hailee R Perrett / Kimmo Rantalainen / Fabien Cannac / Yuhe R Yang / Alba Torrents de la Peña / Rebeca Froes Rocha / Zachary T Berndsen / David Baker / Neil P King / Rogier W Sanders / John P Moore / Shane Crotty / Max Crispin / David C Montefiori / Dennis R Burton / William R Schief / Guido Silvestri / Andrew B Ward /    |
| PubMed 要旨 | 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 ...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. |
 リンク | Nat Commun / PubMed:34376662 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.9 - 20.0 Å |
| 構造データ |  EMDB-23175:  EMDB-23176:  EMDB-23177:  EMDB-23178:  EMDB-23179:  EMDB-23180:  EMDB-23181:  EMDB-23182:  EMDB-23183:  EMDB-23184:  EMDB-23185:  EMDB-23186: EMDB-23218, PDB-7l7t: EMDB-23219, PDB-7l7u: EMDB-23222, PDB-7l85: EMDB-23223, PDB-7l86: EMDB-23224, PDB-7l87: EMDB-23225, PDB-7l88: EMDB-23226, PDB-7l89: EMDB-23227, PDB-7l8a: EMDB-23228, PDB-7l8b: EMDB-23229, PDB-7l8c: EMDB-23230, PDB-7l8d: EMDB-23231, PDB-7l8e: EMDB-23232, PDB-7l8f: EMDB-23233, PDB-7l8g:  EMDB-23234: EMDB-23235, PDB-7l8s: EMDB-23236, PDB-7l8t: EMDB-23237, PDB-7l8u: EMDB-23238, PDB-7l8w: EMDB-23239, PDB-7l8x: EMDB-23240, PDB-7l8y:  EMDB-23241: EMDB-23242, PDB-7l8z: EMDB-23243, PDB-7l90: |
| 化合物 |  ChemComp-NAG: |
| 由来 |
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 キーワード | VIRAL PROTEIN / HIV / vaccine design / protein design / nanoparticles / BG505 / DE NOVO PROTEIN / VIRAL PROTEIN/Immune System / Polyclonal antibodies / EMPEM / VIRAL PROTEIN-Immune System complex |
human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
macaca mulatta (アカゲザル)