Paper

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates

Kuhn, Andreas N, Kröner, Christoph, Schneider, Diana, Singh, Guy, Pride, Michael, Cole, Journey, Kranz, Lena M, Schlereth, Julia, Tan, Charles Y, Ziegenhals, Thomas, Dany, Sarah C, Erbar, Stephanie, Hein, Stephanie, Vogel, Annette B, Grif, Matthew C, Loschko, Jakob, Plaschke, Arianne, Brasky, Kathleen, Bates, Ferdia, Ciolino, Tara, Jansen, Kathrin U, Feuchter, Yvonne, Tompkins, Kristin, Mashalidis, Ellene H, Fesser, Stephanie, Maddur, Mohan S, Lui, Bonny G, Han, Seungil, Swanson, Kena A, Walzer, Kerstin C, Krumm, Stefanie A, Pei-Yong, Shi, Obregon, Jennifer, Kanevsky, Isis, Alfson, Kendra J, Jesionek, Bernadette, Türeci, Özlem, Klamp, Thorsten, Adams-Quack, Petra, Kalina, Warren V, Güler, Alptekin, Rosenbaum, Corinna, Heinen, André P, Lees, Joshua A, Sänger, Bianca, Eisel, David, Wallisch, Ann-Kathrin, Junginger, Hanna, Carrion, Ricardo, Fontes-Garfias, Camila, Scully, Ingrid L, Vormehr, Mathias, Sahasrabudhe, Parag V, Pavliakova, Danka, Ye Che, Sahin, Ugur, Muik, Alexander, Kaushal, Deepak, Hall-Ursone, Shannan, Gazi, Michal, Dormitzer, Philip R

2020

Overview

Abstract To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD ‘up’, two-RBD ‘down’ state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNγ+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (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.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.He., A.G., T.Z., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., A.P.H., P.A., J.S., C.K., 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.He., 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., 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.L., M.M., K.T., M.C.G., S.H., J.A.L.,E.H.M., P.V.S., C.Y.T., D.P., G.S., M.P., I.L.S., T.C., J.O., W.V.K., P.R.D. and 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; J.C., S.H.-U, K.B., R.C., jr., K.J.A. and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; no other relationships or activities that could appear to have influenced the submitted work.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Antiviral agents / Bronchopulmonary infection / CD4 antigen / CD8 antigen / Conformation / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 vaccines / Employees / Immunogenicity / Immunology / Lymphocytes T / mRNA / Pandemics / Patent applications / Population studies / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Vaccination / Vaccines / γ-Interferon