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Basic Characteristics of Mutations
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Mutation Site
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V987P |
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Mutation Site Sentence
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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)). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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33524990
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Title
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BNT162b vaccines protect rhesus macaques from SARS-CoV-2
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Author
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Vogel AB,Kanevsky I,Che Y,Swanson KA,Muik A,Vormehr M,Kranz LM,Walzer KC,Hein S,Guler A,Loschko J,Maddur MS,Ota-Setlik A,Tompkins K,Cole J,Lui BG,Ziegenhals T,Plaschke A,Eisel D,Dany SC,Fesser S,Erbar S,Bates F,Schneider D,Jesionek B,Sanger B,Wallisch AK,Feuchter Y,Junginger H,Krumm SA,Heinen AP,Adams-Quack P,Schlereth J,Schille S,Kroner C,de la Caridad Guimil Garcia R,Hiller T,Fischer L,Sellers RS,Choudhary S,Gonzalez O,Vascotto F,Gutman MR,Fontenot JA,Hall-Ursone S,Brasky K,Griffor MC,Han S,Su AAH,Lees JA,Nedoma NL,Mashalidis EH,Sahasrabudhe PV,Tan CY,Pavliakova D,Singh G,Fontes-Garfias C,Pride M,Scully IL,Ciolino T,Obregon J,Gazi M,Carrion R Jr,Alfson KJ,Kalina WV,Kaushal D,Shi PY,Klamp T,Rosenbaum C,Kuhn AN,Tureci O,Dormitzer PR,Jansen KU,Sahin U
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Journal
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Nature
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Journal Info
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2021 Apr;592(7853):283-289
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Abstract
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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 IFNgamma(+)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 8.2-18.2x 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).
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Sequence Data
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-
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