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

• Published in: bioRxiv
• Main Authors: Vogel, Annette B, Kanevsky, Isis, Ye Che, 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, Ramón De La Caridad Güimil Garcia, Hiller, Thomas, Fischer, Leyla, Sellers, Rani S, Choudhary, Shambhunath, Gonzalez, Olga, Vascotto, Fulvia, Gutman, Matthew R, Fontenot, Jane A, Hall-Ursone, Shannan, Brasky, Kathleen, Grif, Matthew C, Han, Seungil, Andreas Ah Su, 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, Pei-Yong, Shi, Klamp, Thorsten, Rosenbaum, Corinna, Kuhn, Andreas N, Türeci, Özlem, Dormitzer, Philip R, Jansen, Kathrin U, Sahin, Ugur
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.12.2020; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: ACE2; Angiotensin-converting enzyme 2; Antibody response; Avidity; CD4 antigen; CD8 antigen; Compensation; Conformation; Coronaviruses; COVID-19; COVID-19 vaccines; Employees; Glycoproteins; Immunogenicity; Immunology; Lymphocytes T; mRNA; Nanoparticles; Patent applications; Radiography; Respiratory tract; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Trimers; Vaccines; γ-Interferon; United States > US; Germany
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2020.12.11.421008

Abstract 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). Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.H., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.H., A.G., T.Z., F.B., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., S.S., A.P.H., P.A., J.S., A.A.H.S., C.K., R.d.l.C.G.G., L.F. and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.H., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A. J.S., A.A.H.S., T.H., L.F., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S. J.A.L. M.S.M., K.T., A,O.-S., J.A.F., M.C.G., S.H., J.A.L., E.H.M., N.L.N., P.V.S., C.Y.T., D.P., W.V.K., J.O., R.S.S., S,C., T.C., I.L.S., M.W.P., G.S., and P.R.D., K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; M.R.G. received compensation from Pfizer to read and interpret radiographs and CT scans. J.C., S.H.-U, K.B., R.C., Jr., K.J.A. O.G., and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; M.G. is an employee of Texas Biomedical Research Institute, which received compensation from Pfizer to conduct the RT-qPCR viral load quantification; no other relationships or activities that could appear to have influenced the submitted work.