BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

Autor: Vogel AB; BioNTech, Mainz, Germany., Kanevsky I; Pfizer, Pearl River, NY, USA., Che Y; Pfizer, Groton, CT, USA., Swanson KA; Pfizer, Pearl River, NY, USA., Muik A; BioNTech, Mainz, Germany., Vormehr M; BioNTech, Mainz, Germany., Kranz LM; BioNTech, Mainz, Germany., Walzer KC; BioNTech, Mainz, Germany., Hein S; BioNTech, Mainz, Germany., Güler A; BioNTech, Mainz, Germany., Loschko J; Pfizer, Pearl River, NY, USA., Maddur MS; Pfizer, Pearl River, NY, USA., Ota-Setlik A; Pfizer, Pearl River, NY, USA., Tompkins K; Pfizer, Pearl River, NY, USA., Cole J; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Lui BG; BioNTech, Mainz, Germany., Ziegenhals T; BioNTech, Mainz, Germany., Plaschke A; BioNTech, Mainz, Germany., Eisel D; BioNTech, Mainz, Germany., Dany SC; BioNTech, Mainz, Germany., Fesser S; BioNTech, Mainz, Germany., Erbar S; BioNTech, Mainz, Germany., Bates F; BioNTech, Mainz, Germany., Schneider D; BioNTech, Mainz, Germany., Jesionek B; BioNTech, Mainz, Germany., Sänger B; BioNTech, Mainz, Germany., Wallisch AK; BioNTech, Mainz, Germany., Feuchter Y; BioNTech, Mainz, Germany., Junginger H; BioNTech, Mainz, Germany., Krumm SA; BioNTech, Mainz, Germany., Heinen AP; BioNTech, Mainz, Germany., Adams-Quack P; BioNTech, Mainz, Germany., Schlereth J; BioNTech, Mainz, Germany., Schille S; BioNTech, Mainz, Germany., Kröner C; BioNTech, Mainz, Germany., de la Caridad Güimil Garcia R; BioNTech, Mainz, Germany., Hiller T; BioNTech, Mainz, Germany., Fischer L; BioNTech, Mainz, Germany., Sellers RS; Pfizer, Pearl River, NY, USA., Choudhary S; Pfizer, Pearl River, NY, USA., Gonzalez O; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Vascotto F; TRON-Translational Oncology at the University Medical Centre of the Johannes Gutenberg University, Mainz, Germany., Gutman MR; VCA SouthPaws Veterinary Specialists and Emergency Center, Fairfax, VA, USA., Fontenot JA; New Iberia Research Center, New Iberia, LA, USA., Hall-Ursone S; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Brasky K; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Griffor MC; Pfizer, Groton, CT, USA., Han S; Pfizer, Groton, CT, USA., Su AAH; BioNTech, Mainz, Germany., Lees JA; Pfizer, Groton, CT, USA., Nedoma NL; Pfizer, Groton, CT, USA., Mashalidis EH; Pfizer, Groton, CT, USA., Sahasrabudhe PV; Pfizer, Groton, CT, USA., Tan CY; Pfizer, Pearl River, NY, USA., Pavliakova D; Pfizer, Pearl River, NY, USA., Singh G; Pfizer, Pearl River, NY, USA., Fontes-Garfias C; University of Texas Medical Branch, Galveston, TX, USA., Pride M; Pfizer, Pearl River, NY, USA., Scully IL; Pfizer, Pearl River, NY, USA., Ciolino T; Pfizer, Pearl River, NY, USA., Obregon J; Pfizer, Pearl River, NY, USA., Gazi M; Texas Biomedical Research Institute, San Antonio, TX, USA., Carrion R Jr; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Alfson KJ; Texas Biomedical Research Institute, San Antonio, TX, USA., Kalina WV; Pfizer, Pearl River, NY, USA., Kaushal D; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA., Shi PY; University of Texas Medical Branch, Galveston, TX, USA., Klamp T; BioNTech, Mainz, Germany., Rosenbaum C; BioNTech, Mainz, Germany., Kuhn AN; BioNTech, Mainz, Germany., Türeci Ö; BioNTech, Mainz, Germany., Dormitzer PR; Pfizer, Pearl River, NY, USA., Jansen KU; Pfizer, Pearl River, NY, USA., Sahin U; 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.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Apr; Vol. 592 (7853), pp. 283-289. Date of Electronic Publication: 2021 Feb 01.
DOI: 10.1038/s41586-021-03275-y
Abstrakt: 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 USA 1-3 , and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).
Databáze: MEDLINE
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