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BNT162b vaccines protect rhesus macaques from SARS-CoV-2
Nature (London), 2021-04, Vol.592 (7853), p.283-289
[Peer Reviewed Journal]
Copyright Nature Publishing Group Apr 8, 2021 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-021-03275-y ;PMID: 33524990
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Title:
BNT162b vaccines protect rhesus macaques from SARS-CoV-2
Author:
Vogel, Annette B
;
Kanevsky, Isis
;
Che, Ye
;
Swanson, Kena A
;
Muik, Alexander
;
Vormehr, Mathias
;
Kranz, Lena M
;
Walzer, Kerstin C
;
Hein, Stephanie
;
Güler, Alptekin
;
Loschko, Jakob
;
Maddur, Mohan S
;
Ota-Setlik, Ayuko
;
Tompkins, Kristin
;
Cole, Journey
;
Lui, Bonny G
;
Ziegenhals, Thomas
;
Plaschke, Arianne
;
Eisel, David
;
Dany, Sarah C
;
Fesser, Stephanie
;
Erbar, Stephanie
;
Bates, Ferdia
;
Schneider, Diana
;
Jesionek, Bernadette
;
Sänger, Bianca
;
Wallisch, Ann-Kathrin
;
Feuchter, Yvonne
;
Junginger, Hanna
;
Krumm, Stefanie A
;
Heinen, André P
;
Adams-Quack, Petra
;
Schlereth, Julia
;
Schille, Stefan
;
Kröner, Christoph
;
de la Caridad Güimil Garcia, Ramón
;
Hiller, Thomas
;
Fischer, Leyla
;
Sellers, Rani S
;
Choudhary, Shambhunath
;
Gonzalez, Olga
;
Vascotto, Fulvia
;
Gutman, Matthew R
;
Fontenot, Jane A
;
Hall-Ursone, Shannan
;
Brasky, Kathleen
;
Griffor, Matthew C
;
Han, Seungil
;
Su, Andreas A H
;
Lees, Joshua A
;
Nedoma, Nicole L
;
Mashalidis, Ellene H
;
Sahasrabudhe, Parag V
;
Tan, Charles Y
;
Pavliakova, Danka
;
Singh, Guy
;
Fontes-Garfias, Camila
;
Pride, Michael
;
Scully, Ingrid L
;
Ciolino, Tara
;
Obregon, Jennifer
;
Gazi, Michal
;
Carrion, Jr, Ricardo
;
Alfson, Kendra J
;
Kalina, Warren V
;
Kaushal, Deepak
;
Shi, Pei-Yong
;
Klamp, Thorsten
;
Rosenbaum, Corinna
;
Kuhn, Andreas N
;
Türeci, Özlem
;
Dormitzer, Philip R
;
Jansen, Kathrin U
;
Sahin, Ugur
Subjects:
ACE2
;
Aging - immunology
;
Angiotensin-converting enzyme 2
;
Animals
;
Antibodies
;
Antibodies, Neutralizing - immunology
;
Antibodies, Viral - immunology
;
Antibody response
;
Antigens
;
Antigens, Viral - chemistry
;
Antigens, Viral - genetics
;
Antigens, Viral - immunology
;
Avidity
;
Binding sites
;
BNT162 Vaccine
;
CD4 antigen
;
CD8 antigen
;
Cell Line
;
Clinical Trials as Topic
;
Conformation
;
Coronaviruses
;
COVID-19
;
COVID-19 - blood
;
COVID-19 - immunology
;
COVID-19 - prevention & control
;
COVID-19 - therapy
;
COVID-19 - virology
;
COVID-19 Serotherapy
;
COVID-19 Vaccines - administration & dosage
;
COVID-19 Vaccines - chemistry
;
COVID-19 Vaccines - genetics
;
COVID-19 Vaccines - immunology
;
Disease Models, Animal
;
Female
;
Glycoproteins
;
Humans
;
Immunization
;
Immunization, Passive
;
Internationality
;
Lipids
;
Lymphocytes
;
Lymphocytes T
;
Macaca mulatta - immunology
;
Macaca mulatta - virology
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Microscopy
;
Models, Molecular
;
mRNA
;
mRNA Vaccines
;
Nanoparticles
;
Pandemics
;
Proline
;
Protein Multimerization
;
Respiratory System - immunology
;
Respiratory System - virology
;
Respiratory tract
;
RNA, Viral - analysis
;
SARS-CoV-2 - chemistry
;
SARS-CoV-2 - genetics
;
SARS-CoV-2 - immunology
;
Severe acute respiratory syndrome
;
Severe acute respiratory syndrome coronavirus 2
;
Solubility
;
Spike glycoprotein
;
Spike Glycoprotein, Coronavirus - chemistry
;
Spike Glycoprotein, Coronavirus - genetics
;
Spike Glycoprotein, Coronavirus - immunology
;
T-Lymphocytes - immunology
;
Trimers
;
Vaccination
;
Vaccines
;
Vaccines, Synthetic - administration & dosage
;
Vaccines, Synthetic - chemistry
;
Vaccines, Synthetic - genetics
;
Vaccines, Synthetic - immunology
;
Viral diseases
;
Viruses
Is Part Of:
Nature (London), 2021-04, Vol.592 (7853), p.283-289
Description:
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 , and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).
Publisher:
England: Nature Publishing Group
Language:
English
Identifier:
ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/s41586-021-03275-y
PMID: 33524990
Source:
ProQuest One Psychology
MEDLINE
ProQuest Central
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