BNT162b vaccines protect rhesus macaques from SARS-CoV-2

Autor: Bernadette Jesionek, Charles Tan, Christoph Kröner, Jennifer Obregon, Stephanie Hein, Kathleen M. Brasky, Andreas Kuhn, Leyla Fischer, Guy Singh, Diana Schneider, Kathrin U. Jansen, Jane Fontenot, Seungil Han, Michal Gazi, Corinna Rosenbaum, Ingrid L. Scully, Pei Yong Shi, Parag Sahasrabudhe, Stefanie A. Krumm, Hanna Junginger, Camila R. Fontes-Garfias, Julia Schlereth, Bonny Gaby Lui, Mathias Vormehr, Andre P. Heinen, Alptekin Güler, Stephanie Fesser, Sarah C. Dany, Ellene H. Mashalidis, Danka Pavliakova, Shambhunath Choudhary, Mohan S. Maddur, Petra Adams-Quack, Yvonne Feuchter, Matthew C. Griffor, Ferdia Bates, Ramón de la Caridad Güimil Garcia, Tara Ciolino, Özlem Türeci, Stefan Schille, Kena A. Swanson, Kerstin C. Walzer, Alexander Muik, Jakob Loschko, Ayuko Ota-Setlik, Nicole L. Nedoma, Lena M. Kranz, Tompkins Kristin Rachael, Thorsten Klamp, Ugur Sahin, Ann Kathrin Wallisch, Warren Kalina, Olga Gonzalez, Fulvia Vascotto, Philip R. Dormitzer, Ye Che, Kendra J. Alfson, Ricardo Carrion, Thomas Ziegenhals, Shannan Hall-Ursone, Rani S. Sellers, Thomas Hiller, Isis Kanevsky, Matthew R. Gutman, Michael W. Pride, Stephanie Erbar, Bianca Sänger, Deepak Kaushal, Journey Cole, David Eisel, Andreas A.H. Su, Joshua A. Lees, Annette B. Vogel, Arianne Plaschke
Rok vydání: 2021
Předmět:
Zdroj: Nature
ISSN: 1476-4687
0028-0836
Popis: 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 USA1–3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728). BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.
Databáze: OpenAIRE
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