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BNT162b vaccines protect rhesus macaques from SARS-CoV-2.
Nature. 2021 04; 592(7853):283-289.Nat

Abstract

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).

Authors+Show Affiliations

BioNTech, Mainz, Germany.Pfizer, Pearl River, NY, USA.Pfizer, Groton, CT, USA.Pfizer, Pearl River, NY, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.TRON-Translational Oncology at the University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.VCA SouthPaws Veterinary Specialists and Emergency Center, Fairfax, VA, USA.New Iberia Research Center, New Iberia, LA, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.Pfizer, Groton, CT, USA.Pfizer, Groton, CT, USA.BioNTech, Mainz, Germany.Pfizer, Groton, CT, USA.Pfizer, Groton, CT, USA.Pfizer, Groton, CT, USA.Pfizer, Groton, CT, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.University of Texas Medical Branch, Galveston, TX, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.Texas Biomedical Research Institute, San Antonio, TX, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.Texas Biomedical Research Institute, San Antonio, TX, USA.Pfizer, Pearl River, NY, USA.Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.University of Texas Medical Branch, Galveston, TX, USA.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.BioNTech, Mainz, Germany.Pfizer, Pearl River, NY, USA.Pfizer, Pearl River, NY, USA.BioNTech, Mainz, Germany. Ugur.Sahin@biontech.de. TRON-Translational Oncology at the University Medical Centre of the Johannes Gutenberg University, Mainz, Germany. Ugur.Sahin@biontech.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33524990

Citation

Vogel, Annette B., et al. "BNT162b Vaccines Protect Rhesus Macaques From SARS-CoV-2." Nature, vol. 592, no. 7853, 2021, pp. 283-289.
Vogel AB, Kanevsky I, Che Y, et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature. 2021;592(7853):283-289.
Vogel, A. B., Kanevsky, I., Che, Y., Swanson, K. A., Muik, A., Vormehr, M., Kranz, L. M., Walzer, K. C., Hein, S., Güler, A., Loschko, J., Maddur, M. S., Ota-Setlik, A., Tompkins, K., Cole, J., Lui, B. G., Ziegenhals, T., Plaschke, A., Eisel, D., ... Sahin, U. (2021). BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature, 592(7853), 283-289. https://doi.org/10.1038/s41586-021-03275-y
Vogel AB, et al. BNT162b Vaccines Protect Rhesus Macaques From SARS-CoV-2. Nature. 2021;592(7853):283-289. PubMed PMID: 33524990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BNT162b vaccines protect rhesus macaques from SARS-CoV-2. AU - Vogel,Annette B, AU - Kanevsky,Isis, AU - Che,Ye, AU - Swanson,Kena A, AU - Muik,Alexander, AU - Vormehr,Mathias, AU - Kranz,Lena M, AU - Walzer,Kerstin C, AU - Hein,Stephanie, AU - Güler,Alptekin, AU - Loschko,Jakob, AU - Maddur,Mohan S, AU - Ota-Setlik,Ayuko, AU - Tompkins,Kristin, AU - Cole,Journey, AU - Lui,Bonny G, AU - Ziegenhals,Thomas, AU - Plaschke,Arianne, AU - Eisel,David, AU - Dany,Sarah C, AU - Fesser,Stephanie, AU - Erbar,Stephanie, AU - Bates,Ferdia, AU - Schneider,Diana, AU - Jesionek,Bernadette, AU - Sänger,Bianca, AU - Wallisch,Ann-Kathrin, AU - Feuchter,Yvonne, AU - Junginger,Hanna, AU - Krumm,Stefanie A, AU - Heinen,André P, AU - Adams-Quack,Petra, AU - Schlereth,Julia, AU - Schille,Stefan, AU - Kröner,Christoph, AU - de la Caridad Güimil Garcia,Ramón, AU - Hiller,Thomas, AU - Fischer,Leyla, AU - Sellers,Rani S, AU - Choudhary,Shambhunath, AU - Gonzalez,Olga, AU - Vascotto,Fulvia, AU - Gutman,Matthew R, AU - Fontenot,Jane A, AU - Hall-Ursone,Shannan, AU - Brasky,Kathleen, AU - Griffor,Matthew C, AU - Han,Seungil, AU - Su,Andreas A H, AU - Lees,Joshua A, AU - Nedoma,Nicole L, AU - Mashalidis,Ellene H, AU - Sahasrabudhe,Parag V, AU - Tan,Charles Y, AU - Pavliakova,Danka, AU - Singh,Guy, AU - Fontes-Garfias,Camila, AU - Pride,Michael, AU - Scully,Ingrid L, AU - Ciolino,Tara, AU - Obregon,Jennifer, AU - Gazi,Michal, AU - Carrion,Ricardo,Jr AU - Alfson,Kendra J, AU - Kalina,Warren V, AU - Kaushal,Deepak, AU - Shi,Pei-Yong, AU - Klamp,Thorsten, AU - Rosenbaum,Corinna, AU - Kuhn,Andreas N, AU - Türeci,Özlem, AU - Dormitzer,Philip R, AU - Jansen,Kathrin U, AU - Sahin,Ugur, Y1 - 2021/02/01/ PY - 2020/09/01/received PY - 2021/01/20/accepted PY - 2021/2/2/pubmed PY - 2021/4/15/medline PY - 2021/2/1/entrez SP - 283 EP - 289 JF - Nature JO - Nature VL - 592 IS - 7853 N2 - A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728). SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33524990/BNT162b_vaccines_protect_rhesus_macaques_from_SARS_CoV_2_ L2 - https://doi.org/10.1038/s41586-021-03275-y DB - PRIME DP - Unbound Medicine ER -