Details

Autor(en) / Beteiligte

• Vogel, Annette B
• Kanevsky, Isis
• Che, Ye
• Swanson, Kena A
• Muik, Alexander
• Vormehr, Mathias
• Kranz, Lena M
• Walzer, Kerstin C
• Hein, Stephanie
• Güler, Alptekin
• Loschko, Jakob
• Maddur, Mohan S
• Ota-Setlik, Ayuko
• Tompkins, Kristin
• Cole, Journey
• Lui, Bonny G
• Ziegenhals, Thomas
• Plaschke, Arianne
• Eisel, David
• Dany, Sarah C
• Fesser, Stephanie
• Erbar, Stephanie
• Bates, Ferdia
• Schneider, Diana
• Jesionek, Bernadette
• Sänger, Bianca
• Wallisch, Ann-Kathrin
• Feuchter, Yvonne
• Junginger, Hanna
• Krumm, Stefanie A
• Heinen, André P
• Adams-Quack, Petra
• Schlereth, Julia
• Schille, Stefan
• Kröner, Christoph
• de la Caridad Güimil Garcia, Ramón
• Hiller, Thomas
• Fischer, Leyla
• Sellers, Rani S
• Choudhary, Shambhunath
• Gonzalez, Olga
• Vascotto, Fulvia
• Gutman, Matthew R
• Fontenot, Jane A
• Hall-Ursone, Shannan
• Brasky, Kathleen
• Griffor, Matthew C
• Han, Seungil
• Su, Andreas A H
• Lees, Joshua A
• Nedoma, Nicole L
• Mashalidis, Ellene H
• Sahasrabudhe, Parag V
• Tan, Charles Y
• Pavliakova, Danka
• Singh, Guy
• Fontes-Garfias, Camila
• Pride, Michael
• Scully, Ingrid L
• Ciolino, Tara
• Obregon, Jennifer
• Gazi, Michal
• Carrion, Jr, Ricardo
• Alfson, Kendra J
• Kalina, Warren V
• Kaushal, Deepak
• Shi, Pei-Yong
• Klamp, Thorsten
• Rosenbaum, Corinna
• Kuhn, Andreas N
• Türeci, Özlem
• Dormitzer, Philip R
• Jansen, Kathrin U
• Sahin, Ugur

Titel

BNT162b vaccines protect rhesus macaques from SARS-CoV-2

Ist Teil von

• Nature (London), 2021-04, Vol.592 (7853), p.283-289

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 IFNγ CD8 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).