PropertyValue
?:abstract
  • A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD ‘down,’ one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFNγ+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1101/2020.12.11.421008
?:externalLink
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pdf_json_files
  • document_parses/pdf_json/3d00ff4c8f676918f1b0375f3f6a35bf0bb7219b.json
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • BioRxiv; WHO
?:title
  • BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2
?:type
?:year
  • 2020-12-11

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