Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
19
04
2020
accepted:
29
05
2020
pubmed:
28
6
2020
medline:
12
3
2021
entrez:
28
6
2020
Statut:
ppublish
Résumé
mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.
Identifiants
pubmed: 32591390
pii: jimmunol.2000429
doi: 10.4049/jimmunol.2000429
pmc: PMC7372317
mid: NIHMS1601246
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
648-660Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007031
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007038
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007039
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 AI000986
Pays : United States
Informations de copyright
Copyright © 2020 The Authors.
Références
Antimicrob Agents Chemother. 2018 Oct 24;62(11):
pubmed: 30150460
J Virol. 2002 May;76(9):4580-90
pubmed: 11932423
Hum Gene Ther. 2019 Apr;30(4):523-533
pubmed: 30860399
Science. 2009 Apr 10;324(5924):246-51
pubmed: 19251591
Vaccine. 2016 Oct 26;34(45):5442-5448
pubmed: 27622299
mBio. 2018 Apr 3;9(2):
pubmed: 29615508
Pathogens. 2014 Oct 21;3(4):845-74
pubmed: 25436508
J Virol. 2012 Dec;86(24):13397-406
pubmed: 23015719
Vet Pathol. 1995 Nov;32(6):648-60
pubmed: 8592800
Intervirology. 2000;43(4-6):258-72
pubmed: 11251381
Cell. 2019 May 16;177(5):1136-1152.e18
pubmed: 31100268
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
J Immunol. 2016 Jun 15;196(12):5014-23
pubmed: 27183611
EBioMedicine. 2019 Feb;40:574-582
pubmed: 30638863
Front Microbiol. 2018 Oct 31;9:2596
pubmed: 30429836
NPJ Vaccines. 2017 Jul 6;2:18
pubmed: 29263874
Vet Res. 2014;45:85
pubmed: 25163545
Intervirology. 2000;43(4-6):273-81
pubmed: 11251382
J Clin Invest. 2015 Jul 1;125(7):2631-45
pubmed: 26011643
Nat Struct Mol Biol. 2018 Feb;25(2):115-121
pubmed: 29396418
Science. 2012 Sep 14;337(6100):1343-8
pubmed: 22878502
Clin Infect Dis. 2015 Mar 1;60(5):693-702
pubmed: 25416753
Cell. 2016 Jul 28;166(3):596-608
pubmed: 27453466
Nature. 2012 Sep 27;489(7417):526-32
pubmed: 22982990
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
Virology. 2019 Aug;534:96-107
pubmed: 31226666
Mol Ther. 2019 May 8;27(5):974-985
pubmed: 30962164
JCI Insight. 2019 Apr 18;4(8):
pubmed: 30996140
Front Immunol. 2018 Apr 24;9:865
pubmed: 29740451
Vet Pathol. 2014 Mar;51(2):410-26
pubmed: 24363301
RNA Biol. 2012 Nov;9(11):1319-30
pubmed: 23064118
Science. 2011 Aug 12;333(6044):843-50
pubmed: 21737702
Nat Biotechnol. 2011 Feb;29(2):154-7
pubmed: 21217696
Nat Med. 2014 Feb;20(2):143-51
pubmed: 24412922
J Virol. 2005 Dec;79(23):14793-803
pubmed: 16282479
ILAR J. 2015;56(1):44-52
pubmed: 25991697
Vet Pathol. 2012 Nov;49(6):900-12
pubmed: 22461226
Methods Mol Biol. 2018;1836:401-430
pubmed: 30151585
Nat Commun. 2018 Oct 1;9(1):3999
pubmed: 30275522
Viruses. 2010;2(8):1530-1563
pubmed: 21442033
Science. 2011 Aug 12;333(6044):850-6
pubmed: 21798894
J Virol. 2020 Jan 31;94(4):
pubmed: 31748388
Cell Rep. 2018 Nov 13;25(7):1982-1993.e4
pubmed: 30428362
J Clin Invest. 2016 Feb;126(2):605-10
pubmed: 26731473
J Clin Virol. 2016 Jun;79:44-50
pubmed: 27085509
Lancet Infect Dis. 2018 Oct;18(10):e312-e322
pubmed: 29891332
Clin Pharmacokinet. 2018 Mar;57(3):367-377
pubmed: 28639229
mBio. 2016 Apr 19;7(2):e00417-16
pubmed: 27094330
J Exp Med. 2013 Jul 29;210(8):1493-500
pubmed: 23857983
mSphere. 2018 Sep 19;3(5):
pubmed: 30232169
Expert Opin Drug Discov. 2018 Dec;13(12):1131-1139
pubmed: 30362841
Pharm Res. 2019 Feb 5;36(3):47
pubmed: 30721414