8TYE

Lassa GPC (strain Josiah) bound to rabbit polyclonal fusion-peptide-targeting antibody FP-1

8TYE の概要

• エントリーDOI: 10.2210/pdb8tye/pdb
• EMDBエントリー: 41715
• 分子名称: Polyclonal Fv heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, Polyclonal Fv light chain, ... (10 entities in total)
• 機能のキーワード: lassa virus glycoprotein complex, gpc, immune complex, antibody, polyclonal antibody, base antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Lassa virus (strain Mouse/Sierra Leone/Josiah/1976); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 252445.84

構造登録者

Perrett, H.R.,Brouwer, P.J.M.,Ward, A.B. (登録日: 2023-08-25, 公開日: 2024-09-11, 最終更新日: 2024-09-25)

主引用文献

Brouwer, P.J.M.,Perrett, H.R.,Beaumont, T.,Nijhuis, H.,Kruijer, S.,Burger, J.A.,Bontjer, I.,Lee, W.H.,Ferguson, J.A.,Schauflinger, M.,Muller-Krauter, H.,Sanders, R.W.,Strecker, T.,van Gils, M.J.,Ward, A.B.
Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses.
Cell Rep, 43:114708-114708, 2024

PubMed Abstract: Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.

PubMed: 39243373
DOI: 10.1016/j.celrep.2024.114708

実験手法

ELECTRON MICROSCOPY (3.8 Å)