Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model.
Animals
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Neutralizing
/ administration & dosage
Antibodies, Viral
/ administration & dosage
Cricetinae
Disease Models, Animal
Epitopes
/ immunology
Female
Orthohantavirus
/ immunology
Hantavirus Infections
/ immunology
Mice
Mice, Inbred BALB C
Viral Envelope Proteins
/ immunology
Andes virus
MAb
Sin Nombre virus
hantavirus
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
24 03 2020
24 03 2020
Historique:
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
13
3
2021
Statut:
epublish
Résumé
Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyén, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyén outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian hamster model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action.
Identifiants
pubmed: 32209676
pii: mBio.00028-20
doi: 10.1128/mBio.00028-20
pmc: PMC7157512
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007647
Pays : United States
Informations de copyright
Copyright © 2020 Duehr et al.
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