anyone open this up10 Sep 2020 14:56
A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
Annette Vogel, Isis Kanevsky, Ye Che, Kena Swanson, Alexander Muik, Mathias Vormehr, Lena Kranz, Kerstin Walzer, Stephanie Hein, Alptekin Gueler, Jakob Loschko, Mohan Maddur, Kristin Tompkins, Journey Cole, Bonny Gaby Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah Dany, Stephanie Fesser, Stephanie Erbar, ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Saenger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie Krumm, Andre Heinen, Petra Adams-Quack, Julia Schlereth, Christoph Kroener, Shannan Hall-Ursone, Kathleen Brasky, Matthew C Griffor, Seungil Han, Joshua Lees, Ellene Mashalidis, Parag Sahasrabudhe, Charles Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid Scully, tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion, Kendra Alfson, Warren Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas Kuhn, Oezlem Tuereci, Philip Dormitzer, Kathrin Jansen, Ugur Sahin
bioRxiv 2020.09.08.280818; doi: https://doi.org/10.1101/2020.09.08.280818
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 IFNy+ 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).