BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

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, 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

A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD ‘down,’ one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFNγ+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).