 BNT162b vaccines protect rhesus macaques from SARS-CoV-2Annette 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 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 ()
Nature, 2021, vol. 592, issue 7853, 283-289 Abstract: 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 (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). Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:592:y:2021:i:7853:d:10.1038_s41586-021-03275-y Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-021-03275-y Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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