TY - JOUR T1 - BNT162b vaccines protect rhesus macaques from SARS-CoV-2. AU - Vogel,Annette B, AU - Kanevsky,Isis, AU - Che,Ye, AU - Swanson,Kena A, AU - Muik,Alexander, AU - Vormehr,Mathias, AU - Kranz,Lena M, AU - Walzer,Kerstin C, AU - Hein,Stephanie, AU - Güler,Alptekin, AU - Loschko,Jakob, AU - Maddur,Mohan S, AU - Ota-Setlik,Ayuko, AU - Tompkins,Kristin, AU - Cole,Journey, AU - Lui,Bonny G, AU - Ziegenhals,Thomas, AU - Plaschke,Arianne, AU - Eisel,David, AU - Dany,Sarah C, AU - Fesser,Stephanie, AU - Erbar,Stephanie, AU - Bates,Ferdia, AU - Schneider,Diana, AU - Jesionek,Bernadette, AU - Sänger,Bianca, AU - Wallisch,Ann-Kathrin, AU - Feuchter,Yvonne, AU - Junginger,Hanna, AU - Krumm,Stefanie A, AU - Heinen,André P, AU - Adams-Quack,Petra, AU - Schlereth,Julia, AU - Schille,Stefan, AU - Kröner,Christoph, AU - de la Caridad Güimil Garcia,Ramón, AU - Hiller,Thomas, AU - Fischer,Leyla, AU - Sellers,Rani S, AU - Choudhary,Shambhunath, AU - Gonzalez,Olga, AU - Vascotto,Fulvia, AU - Gutman,Matthew R, AU - Fontenot,Jane A, AU - Hall-Ursone,Shannan, AU - Brasky,Kathleen, AU - Griffor,Matthew C, AU - Han,Seungil, AU - Su,Andreas A H, AU - Lees,Joshua A, AU - Nedoma,Nicole L, AU - Mashalidis,Ellene H, AU - Sahasrabudhe,Parag V, AU - Tan,Charles Y, AU - Pavliakova,Danka, AU - Singh,Guy, AU - Fontes-Garfias,Camila, AU - Pride,Michael, AU - Scully,Ingrid L, AU - Ciolino,Tara, AU - Obregon,Jennifer, AU - Gazi,Michal, AU - Carrion,Ricardo,Jr AU - Alfson,Kendra J, AU - Kalina,Warren V, AU - Kaushal,Deepak, AU - Shi,Pei-Yong, AU - Klamp,Thorsten, AU - Rosenbaum,Corinna, AU - Kuhn,Andreas N, AU - Türeci,Özlem, AU - Dormitzer,Philip R, AU - Jansen,Kathrin U, AU - Sahin,Ugur, Y1 - 2021/02/01/ PY - 2020/09/01/received PY - 2021/01/20/accepted PY - 2021/2/2/pubmed PY - 2021/4/15/medline PY - 2021/2/1/entrez SP - 283 EP - 289 JF - Nature JO - Nature VL - 592 IS - 7853 N2 - 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). SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33524990/BNT162b_vaccines_protect_rhesus_macaques_from_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -