qefts96

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?: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 States1-3. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).
?:creator	<https://research.tib.eu/covid-19/entity/Vogel%2C_Annette_B%3B_Kanevsky%2C_Isis%3B_Che%2C_Ye%3B_Swanson%2C_Kena_A%3B_Muik%2C_Alexander%3B_Vormehr%2C_Mathias%3B_Kranz%2C_Lena_M%3B_Walzer%2C_Kerstin_C%3B_Hein%2C_Stephanie%3B_G%C3%BCler%2C_Alptekin%3B_Loschko%2C_Jakob%3B_Maddur%2C_Mohan_S%3B_Ota-Setlik%2C_Ayuko%3B_Tompkins%2C_Kristin%3B_Cole%2C_Journey%3B_Lui%2C_Bonny_G%3B_Ziegenhals%2C_Thomas%3B_Plaschke%2C_Arianne%3B_Eisel%2C_David%3B_Dany%2C_Sarah_C%3B_Fesser%2C_Stephanie%3B_Erbar%2C_Stephanie%3B_Bates%2C_Ferdia%3B_Schneider%2C_Diana%3B_Jesionek%2C_Bernadette%3B_S%C3%A4nger%2C_Bianca%3B_Wallisch%2C_Ann-Kathrin%3B_Feuchter%2C_Yvonne%3B_Junginger%2C_Hanna%3B_Krumm%2C_Stefanie_A%3B_Heinen%2C_Andr%C3%A9_P%3B_Adams-Quack%2C_Petra%3B_Schlereth%2C_Julia%3B_Schille%2C_Stefan%3B_Kr%C3%B6ner%2C_Christoph%3B_de_la_Caridad_G%C3%BCimil_Garcia%2C_Ram%C3%B3n%3B_Hiller%2C_Thomas%3B_Fischer%2C_Leyla%3B_Sellers%2C_Rani_S%3B_Choudhary%2C_Shambhunath%3B_Gonzalez%2C_Olga%3B_Vascotto%2C_Fulvia%3B_Gutman%2C_Matthew_R%3B_Fontenot%2C_Jane_A%3B_Hall-Ursone%2C_Shannan%3B_Brasky%2C_Kathleen%3B_Griffor%2C_Matthew_C%3B_Han%2C_Seungil%3B_Su%2C_Andreas_A_H%3B_Lees%2C_Joshua_A%3B_Nedoma%2C_Nicole_L%3B_Mashalidis%2C_Ellene_H%3B_Sahasrabudhe%2C_Parag_V%3B_Tan%2C_Charles_Y%3B_Pavliakova%2C_Danka%3B_Singh%2C_Guy%3B_Fontes-Garfias%2C_Camila%3B_Pride%2C_Michael%3B_Scully%2C_Ingrid_L%3B_Ciolino%2C_Tara%3B_Obregon%2C_Jennifer%3B_Gazi%2C_Michal%3B_Carrion%2C_Ricardo%3B_Alfson%2C_Kendra_J%3B_Kalina%2C_Warren_V%3B_Kaushal%2C_Deepak%3B_Shi%2C_Pei-Yong%3B_Klamp%2C_Thorsten%3B_Rosenbaum%2C_Corinna%3B_Kuhn%2C_Andreas_N%3B_T%C3%BCreci%2C_%C3%96zlem%3B_Dormitzer%2C_Philip_R%3B_Jansen%2C_Kathrin_U%3B_Sahin%2C_Ugur>
?:doi	<https://research.tib.eu/covid-19/entity/10.1038/s41586-021-03275-y>
?:doi	10.1038/s41586-021-03275-y
?:journal	Nature
?:license	unk
?:pmid	<https://research.tib.eu/covid-19/entity/33524990>
?:pmid	33524990
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
?:source	Medline
?:title	Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2.
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:year	2021-02-01

Property

Value

?: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 States1-3. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).

?:creator