COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Neutralizing
/ administration & dosage
Antiviral Agents
/ administration & dosage
COVID-19
/ blood
Disease Models, Animal
Drug Evaluation, Preclinical
Female
Humans
Lung
/ metabolism
Macaca fascicularis
Male
Mesocricetus
Mice
Mice, Transgenic
SARS-CoV-2
/ immunology
Tissue Distribution
Viral Load
COVID-19 Drug Treatment
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 10 2021
20 10 2021
Historique:
received:
15
02
2021
accepted:
24
09
2021
entrez:
21
10
2021
pubmed:
22
10
2021
medline:
3
11
2021
Statut:
epublish
Résumé
Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.
Identifiants
pubmed: 34671037
doi: 10.1038/s41467-021-26354-0
pii: 10.1038/s41467-021-26354-0
pmc: PMC8528857
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antiviral Agents
0
COVA1-18
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6097Subventions
Organisme : NIAID NIH HHS
ID : R21 AI157606
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-002022
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-11-INBS-0008
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : R21AI157606
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1170236
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-004923
Organisme : Department of Defense
ID : W81XWH-20-1-0270
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2021. The Author(s).
Références
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Nature. 2020 Aug;584(7819):120-124
pubmed: 32454512
Nat Med. 2021 Apr;27(4):622-625
pubmed: 33654292
N Engl J Med. 2021 Jan 21;384(3):229-237
pubmed: 33113295
Cell. 2020 Aug 6;182(3):744-753.e4
pubmed: 32553273
Cell. 2020 Aug 20;182(4):812-827.e19
pubmed: 32697968
PLoS Comput Biol. 2021 Mar 17;17(3):e1008785
pubmed: 33730053
PLoS Comput Biol. 2021 Mar 1;17(3):e1008752
pubmed: 33647008
N Engl J Med. 2021 Jan 21;384(3):238-251
pubmed: 33332778
Nature. 2020 Aug;584(7821):443-449
pubmed: 32668443
Front Immunol. 2020 Dec 18;11:614256
pubmed: 33391285
Science. 2021 Feb 19;371(6531):850-854
pubmed: 33495308
Emerg Microbes Infect. 2020 Dec;9(1):2433-2445
pubmed: 33073694
Nature. 2021 Apr;592(7852):116-121
pubmed: 33106671
Cell. 2021 Aug 5;184(16):4203-4219.e32
pubmed: 34242577
Nat Med. 2020 Sep;26(9):1422-1427
pubmed: 32651581
Cell. 2020 Jul 9;182(1):73-84.e16
pubmed: 32425270
Cell. 2021 Jan 7;184(1):64-75.e11
pubmed: 33275900
Front Microbiol. 2020 Sep 04;11:2020
pubmed: 33013745
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32692348
Cell. 2021 Mar 4;184(5):1188-1200.e19
pubmed: 33577765
Euro Surveill. 2020 Jan;25(3):
pubmed: 31992387
Nature. 2020 Oct;586(7830):509-515
pubmed: 32967005
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):
pubmed: 34417349
Cell Host Microbe. 2021 Apr 14;29(4):529-539.e3
pubmed: 33705729
Nature. 2020 May;581(7809):465-469
pubmed: 32235945
Front Microbiol. 2020 Apr 24;11:658
pubmed: 32390971
Science. 2020 Aug 21;369(6506):1014-1018
pubmed: 32540904
Sci Adv. 2021 Apr 16;7(16):
pubmed: 33863729
Clin Imaging. 2021 Feb;70:101-110
pubmed: 33142125
Science. 2020 Nov 27;370(6520):1110-1115
pubmed: 33037066
Immunity. 2020 Dec 15;53(6):1272-1280.e5
pubmed: 33242394
Nature. 2020 Sep;585(7826):584-587
pubmed: 32698191
Front Immunol. 2019 Jun 07;10:1296
pubmed: 31231397
Proc Natl Acad Sci U S A. 2021 Feb 23;118(8):
pubmed: 33536313
Lancet Infect Dis. 2020 Jun;20(6):697-706
pubmed: 32224310
Cell Rep. 2021 Mar 23;34(12):108890
pubmed: 33713594
Sci Transl Med. 2021 May 12;13(593):
pubmed: 33820835
N Engl J Med. 2021 Mar 11;384(10):905-914
pubmed: 33356051
Cell. 2020 Oct 29;183(3):739-751.e8
pubmed: 32991842
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Nature. 2021 May;593(7857):130-135
pubmed: 33684923
Clin Pharmacol Ther. 2008 Nov;84(5):548-58
pubmed: 18784655
Radiology. 2020 Jun;295(3):715-721
pubmed: 32053470
Nat Commun. 2020 Nov 13;11(1):5752
pubmed: 33188207