7L7F

Cryo-EM structure of human ACE2 receptor bound to protein encoded by vaccine candidate BNT162b1

7L7F の概要

• エントリーDOI: 10.2210/pdb7l7f/pdb
• EMDBエントリー: 23211
• 分子名称: Angiotensin-converting enzyme 2, Spike glycoprotein, Envelope glycoprotein fusion (2 entities in total)
• 機能のキーワード: sars-cov-2, covid19, bnt162b1, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 244093.95

構造登録者

Lees, J.A.,Han, S. (登録日: 2020-12-28, 公開日: 2021-02-24, 最終更新日: 2024-11-20)

主引用文献

Vogel, A.B.,Kanevsky, I.,Che, Y.,Swanson, K.A.,Muik, A.,Vormehr, M.,Kranz, L.M.,Walzer, K.C.,Hein, S.,Guler, A.,Loschko, J.,Maddur, M.S.,Ota-Setlik, A.,Tompkins, K.,Cole, J.,Lui, B.G.,Ziegenhals, T.,Plaschke, A.,Eisel, D.,Dany, S.C.,Fesser, S.,Erbar, S.,Bates, F.,Schneider, D.,Jesionek, B.,Sanger, B.,Wallisch, A.K.,Feuchter, Y.,Junginger, H.,Krumm, S.A.,Heinen, A.P.,Adams-Quack, P.,Schlereth, J.,Schille, S.,Kroner, C.,de la Caridad Guimil Garcia, R.,Hiller, T.,Fischer, L.,Sellers, R.S.,Choudhary, S.,Gonzalez, O.,Vascotto, F.,Gutman, M.R.,Fontenot, J.A.,Hall-Ursone, S.,Brasky, K.,Griffor, M.C.,Han, S.,Su, A.A.H.,Lees, J.A.,Nedoma, N.L.,Mashalidis, E.H.,Sahasrabudhe, P.V.,Tan, C.Y.,Pavliakova, D.,Singh, G.,Fontes-Garfias, C.,Pride, M.,Scully, I.L.,Ciolino, T.,Obregon, J.,Gazi, M.,Carrion Jr., R.,Alfson, K.J.,Kalina, W.V.,Kaushal, D.,Shi, P.Y.,Klamp, T.,Rosenbaum, C.,Kuhn, A.N.,Tureci, O.,Dormitzer, P.R.,Jansen, K.U.,Sahin, U.
BNT162b vaccines protect rhesus macaques from SARS-CoV-2.
Nature, 592:283-289, 2021

PubMed Abstract: A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4 and IFNγCD8 T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).

PubMed: 33524990
DOI: 10.1038/s41586-021-03275-y

実験手法

ELECTRON MICROSCOPY (3.24 Å)