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TitleBNT162b vaccines protect rhesus macaques from SARS-CoV-2.
Journal, issue, pagesNature, Vol. 592, Issue 7853, Page 283-289, Year 2021
Publish dateFeb 1, 2021
AuthorsAnnette 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 /
PubMed AbstractA 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).
External linksNature / PubMed:33524990
MethodsEM (single particle)
Resolution3.24 - 3.29 Å
Structure data

23211

7l7f

EMDB-23211, PDB-7l7f:
Cryo-EM structure of human ACE2 receptor bound to protein encoded by vaccine candidate BNT162b1
Method: EM (single particle) / Resolution: 3.24 Å

23215

7l7k

EMDB-23215, PDB-7l7k:
Cryo-EM structure of protein encoded by vaccine candidate BNT162b2
Method: EM (single particle) / Resolution: 3.29 Å

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / SARS-CoV-2 / COVID19 / BNT162b1 / BNT162b2

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