• Nature · Apr 2021

    BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

    • 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, and Ugur Sahin.
    • BioNTech, Mainz, Germany.
    • Nature. 2021 Apr 1; 592 (7853): 283-289.

    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 (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 USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).

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