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

View ORCID ProfileAnnette 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, 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, Christoph Kröner, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, View ORCID ProfileSeungil Han, Joshua A. Lees, 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 Jr., 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, Ugur Sahin
doi: https://doi.org/10.1101/2020.09.08.280818
Annette B. Vogel
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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  • ORCID record for Annette B. Vogel
Isis Kanevsky
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Ye Che
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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Kena A. Swanson
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Alexander Muik
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Mathias Vormehr
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Lena M. Kranz
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Kerstin C. Walzer
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Stephanie Hein
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Alptekin Güler
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Jakob Loschko
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Mohan S. Maddur
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Kristin Tompkins
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Journey Cole
4Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr, San Antonio, TX 78227, United States
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Bonny G. Lui
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Thomas Ziegenhals
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Arianne Plaschke
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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David Eisel
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Sarah C. Dany
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Stephanie Fesser
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Stephanie Erbar
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Ferdia Bates
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Diana Schneider
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Bernadette Jesionek
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Bianca Sänger
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Ann-Kathrin Wallisch
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Yvonne Feuchter
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Hanna Junginger
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Stefanie A. Krumm
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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André P. Heinen
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Petra Adams-Quack
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Julia Schlereth
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Christoph Kröner
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Shannan Hall-Ursone
4Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr, San Antonio, TX 78227, United States
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Kathleen Brasky
4Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr, San Antonio, TX 78227, United States
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Matthew C. Griffor
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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Seungil Han
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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  • ORCID record for Seungil Han
Joshua A. Lees
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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Ellene H. Mashalidis
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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Parag V. Sahasrabudhe
3Pfizer, 280 Shennecossett Rd., Groton, CT 06340, United States
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Charles Y. Tan
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Danka Pavliakova
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Guy Singh
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Camila Fontes-Garfias
5University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States
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Michael Pride
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Ingrid L. Scully
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Tara Ciolino
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Jennifer Obregon
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Michal Gazi
6Texas Biomedical Research Institute, 8715 W Military Dr, San Antonio, TX 78227, United States
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Ricardo Carrion Jr.
4Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr, San Antonio, TX 78227, United States
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Kendra J. Alfson
6Texas Biomedical Research Institute, 8715 W Military Dr, San Antonio, TX 78227, United States
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Warren V. Kalina
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Deepak Kaushal
4Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr, San Antonio, TX 78227, United States
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Pei-Yong Shi
5University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States
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Thorsten Klamp
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Corinna Rosenbaum
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Andreas N. Kuhn
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Özlem Türeci
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
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Philip R. Dormitzer
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Kathrin U. Jansen
2Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, United States
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Ugur Sahin
1BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
7TRON gGmbH – Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Freiligrathstraße 12, 55131 Mainz, Germany
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  • For correspondence: Ugur.Sahin@biontech.de
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
Annette 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, 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, Christoph Kröner, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Joshua A. Lees, 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 Jr., 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, Ugur Sahin
bioRxiv 2020.09.08.280818; doi: https://doi.org/10.1101/2020.09.08.280818
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A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
Annette 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, 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, Christoph Kröner, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Joshua A. Lees, 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 Jr., 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, Ugur Sahin
bioRxiv 2020.09.08.280818; doi: https://doi.org/10.1101/2020.09.08.280818

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