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RESEARCH PRODUCT

BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

Oezlem TuereciArianne PlaschkeTompkins Kristin RachaelAndre P. HeinenJoshua A. LeesStefan SchilleKena A. SwansonDeepak KaushalKathrin U. JansenCorinna RosenbaumDanka PavliakovaUgur SahinShannan Hall-ursoneRani S. SellersJourney ColeParag SahasrabudheStefanie A. KrummFerdia BatesStephanie ErbarIsis KanevskyBianca SaengerMichal GaziAnnette B. VogelKathleen M. BraskyMatthew R. GutmanHanna JungingerSarah C. DanyNicole L. NedomaLena M. KranzCamila R. Fontes-garfiasJulia SchlerethShambhunath ChoudharyAndreas A.h. SuRamon De La Caridad Gueimil GarciaSeungil HanThorsten KlampAyuko Ota-setlikBonny Gaby LuiMichael W. PrideFulvia VascottoAnn-kathrin WallischIngrid L. ScullyStephanie HeinDavid EiselCharles TanPei Yong ShiMathias VormehrPhilip R. DormitzerOlga GonzalezKendra J. AlfsonThomas HillerBernadette JesionekThomas ZiegenhalsStephanie FesserJennifer ObregonPetra Adams-quackMatthew C. GrifforAlptekin GuelerYvonne FeuchterAlexander MuikJakob LoschkoJane FontenotChristoph KroenerRicardo CarrionLeyla FischerWarren KalinaAndreas N. KuhnYe CheGuy SinghDiana SchneiderMohan S. MaddurKerstin C. WalzerTara CiolinoEllene H. Mashalidis

subject

Vaccinationchemistry.chemical_classificationMessenger RNACoronavirus disease 2019 (COVID-19)chemistryHigh aviditySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologyGlycoproteinVirologyCD8Transmembrane protein

description

AbstractA 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).

yearjournalcountryeditionlanguage
2020-12-11
https://doi.org/10.1101/2020.12.11.421008