A combination of two human monoclonal antibodies cures symptomatic rabies.
immunotherapeutics
monoclonal antibody therapy
neglected diseases
neuroinfectious diseases
rabies virus
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
06 11 2020
06 11 2020
Historique:
received:
29
04
2020
revised:
26
08
2020
accepted:
27
08
2020
pubmed:
19
9
2020
medline:
19
8
2021
entrez:
18
9
2020
Statut:
ppublish
Résumé
Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post-exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case-fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of antibodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody-based therapeutic approach for symptomatic rabies.
Identifiants
pubmed: 32945125
doi: 10.15252/emmm.202012628
pmc: PMC7645379
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Rabies Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12628Subventions
Organisme : INFECT-ERA 2016
ID : INFECT-ERA 2016 ToRRENT
Organisme : Agence Nationale de la Recherche (ANR)
ID : 16-IFEC-0006-01
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : IZSVe RC 08/09
Organisme : VIR Biotechnology
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Lancet Infect Dis. 2019 Dec;19(12):1355-1362
pubmed: 31570311
Clin Infect Dis. 2018 Jan 18;66(3):387-395
pubmed: 29020321
Sci Rep. 2019 Aug 21;9(1):12171
pubmed: 31434934
J Med Virol. 2010 Jul;82(7):1255-65
pubmed: 20513093
Mol Genet Metab. 2018 Jul;124(3):184-188
pubmed: 29793829
EMBO Mol Med. 2016 Mar 31;8(4):407-21
pubmed: 26992832
J Vis Exp. 2008 Oct 06;(20):
pubmed: 19078946
Sci Rep. 2017 Feb 06;7:41889
pubmed: 28165503
Science. 2016 Aug 19;353(6301):823-6
pubmed: 27417494
Nat Methods. 2012 Jun 28;9(7):690-6
pubmed: 22743774
J Biol Chem. 2013 Dec 6;288(49):35452-65
pubmed: 24163366
J Psychopharmacol. 2007 Mar;21(2):134-5
pubmed: 17329288
PLoS Negl Trop Dis. 2013 Sep 19;7(9):e2375
pubmed: 24069466
Infect Disord Drug Targets. 2011 Jun;11(3):251-99
pubmed: 21488832
J Clin Microbiol. 2010 Nov;48(11):3970-8
pubmed: 20739489
Clin Infect Dis. 2020 Jun 17;:
pubmed: 32556113
Nat Commun. 2020 Jan 30;11(1):596
pubmed: 32001700
Front Cell Neurosci. 2020 Mar 20;14:65
pubmed: 32265666
Antiviral Res. 2014 Oct;110:132-41
pubmed: 25108172
PLoS Negl Trop Dis. 2010 Nov 30;4(11):e839
pubmed: 21152052
Pediatr Neurol. 2017 Feb;67:23-35
pubmed: 28089765
PLoS Negl Trop Dis. 2015 Apr 16;9(4):e0003709
pubmed: 25881058
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
Mol Biol Rep. 2019 Oct;46(5):5257-5272
pubmed: 31327120
Rev Sci Tech. 2018 Aug;37(2):569-580
pubmed: 30747124
J Pharm Pharmacol. 1968 Apr;20(4):302-4
pubmed: 4384609
N Engl J Med. 2005 Jun 16;352(24):2508-14
pubmed: 15958806
Trop Med Infect Dis. 2017 Mar 24;2(2):
pubmed: 30270864
Front Immunol. 2019 Jun 07;10:1296
pubmed: 31231397
J Neurol Sci. 2014 Apr 15;339(1-2):8-14
pubmed: 24582283
Can J Neurol Sci. 2016 Jan;43(1):44-51
pubmed: 26639059
Curr Opin Infect Dis. 2018 Feb;31(1):93-101
pubmed: 29293476
J Gen Virol. 2019 Aug;100(8):1171-1186
pubmed: 31237530
Vaccine. 2019 Oct 3;37 Suppl 1:A132-A139
pubmed: 30503659
Sci Rep. 2019 Mar 15;9(1):4658
pubmed: 30874605
PLoS Negl Trop Dis. 2009 Oct 06;3(10):e535
pubmed: 19806203
Neurosci Lett. 2009 Oct 16;464(1):29-33
pubmed: 19679164