|Entry||Database: PDB / ID: 7l7k|
|Title||Cryo-EM structure of protein encoded by vaccine candidate BNT162b2|
|Keywords||VIRAL PROTEIN / SARS-CoV-2 / COVID19 / BNT162b2|
|Function / homology|
Function and homology information
suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / host cell surface receptor binding / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / viral entry into host cell / fusion of virus membrane with host endosome membrane / viral envelope ...suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / host cell surface receptor binding / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / viral entry into host cell / fusion of virus membrane with host endosome membrane / viral envelope / go:0009405: / host cell plasma membrane / virion membrane / integral component of membrane / identical protein binding
Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / in:ipr027400: / Spike glycoprotein S2, coronavirus / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Spike receptor binding domain superfamily, coronavirus / Spike glycoprotein S2 superfamily, coronavirus / Coronavirus spike glycoprotein S1, C-terminal
|Biological species||Severe acute respiratory syndrome coronavirus 2|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.29 Å|
|Authors||Lees, J.A. / Han, S.|
|Citation||Journal: Nature / Year: 2021|
Title: BNT162b vaccines protect rhesus macaques from SARS-CoV-2.
Authors: Annette B Vogel / Isis Kanevsky / Ye Che / Kena A Swanson / Alexander Muik / Mathias Vormehr / Lena M Kranz / Kerstin C Walzer / Stephanie Hein / Alptekin Güler / Jakob Loschko / Mohan S ...Authors: Annette B Vogel / Isis Kanevsky / Ye Che / Kena A Swanson / Alexander Muik / Mathias Vormehr / Lena M Kranz / Kerstin C Walzer / Stephanie Hein / Alptekin Güler / Jakob Loschko / Mohan S Maddur / Ayuko Ota-Setlik / Kristin Tompkins / Journey Cole / Bonny G Lui / Thomas Ziegenhals / Arianne Plaschke / David Eisel / Sarah C Dany / Stephanie Fesser / Stephanie Erbar / Ferdia Bates / Diana Schneider / Bernadette Jesionek / Bianca Sänger / Ann-Kathrin Wallisch / Yvonne Feuchter / Hanna Junginger / Stefanie A Krumm / André P Heinen / Petra Adams-Quack / Julia Schlereth / Stefan Schille / Christoph Kröner / Ramón de la Caridad Güimil Garcia / Thomas Hiller / Leyla Fischer / Rani S Sellers / Shambhunath Choudhary / Olga Gonzalez / Fulvia Vascotto / Matthew R Gutman / Jane A Fontenot / Shannan Hall-Ursone / Kathleen Brasky / Matthew C Griffor / Seungil Han / Andreas A H Su / Joshua A Lees / Nicole L Nedoma / Ellene H Mashalidis / Parag V Sahasrabudhe / Charles Y Tan / Danka Pavliakova / Guy Singh / Camila Fontes-Garfias / Michael Pride / Ingrid L Scully / Tara Ciolino / Jennifer Obregon / Michal Gazi / Ricardo Carrion / Kendra J Alfson / Warren V Kalina / Deepak Kaushal / Pei-Yong Shi / Thorsten Klamp / Corinna Rosenbaum / Andreas N Kuhn / Özlem Türeci / Philip R Dormitzer / Kathrin U Jansen / Ugur Sahin /
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 ...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).
SummaryFull reportAbout validation report
|Structure viewer||Molecule: |
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B: Spike glycoprotein
C: Spike glycoprotein
A: Spike glycoprotein
Mass: 141263.344 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
|Component||Name: Protein encoded by vaccine candidate BNT162b2 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT|
|Molecular weight||Experimental value: NO|
|Source (natural)||Organism: Severe acute respiratory syndrome coronavirus 2|
|Source (recombinant)||Organism: Homo sapiens (human)|
|Buffer solution||pH: 7.5|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 50.22 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Software||Name: PHENIX / Version: dev_3594: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Symmetry||Point symmetry: C3 (3 fold cyclic)|
|3D reconstruction||Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58295 / Symmetry type: POINT|
|Refine LS restraints|
-Aug 12, 2020. New: Covid-19 info
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-Mar 5, 2020. Novel coronavirus structure data
Novel coronavirus structure data
- International Committee on Taxonomy of Viruses (ICTV) defined the short name of the 2019 coronavirus as "SARS-CoV-2".
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 - nature microbiology
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