Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection.
Adult
Aerosols
/ administration & dosage
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antigens, Viral
/ immunology
Cryoelectron Microscopy
Disease Models, Animal
Encephalitis Virus, Eastern Equine
/ immunology
Encephalomyelitis, Equine
/ immunology
Epitopes
/ chemistry
Female
Glycoproteins
/ immunology
Humans
Mice
Models, Molecular
Mutagenesis
/ genetics
Neutralization Tests
Protein Binding
Protein Domains
Recombinant Proteins
/ immunology
Sindbis Virus
/ immunology
Virion
/ immunology
Virus Internalization
Eastern equine
aerosol
encephalitis
human antibodies
monoclonal
neutralizing
prophylaxis
therapy
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
23 12 2020
23 12 2020
Historique:
received:
24
07
2020
revised:
23
09
2020
accepted:
06
11
2020
pubmed:
11
12
2020
medline:
19
5
2021
entrez:
10
12
2020
Statut:
ppublish
Résumé
Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has recently shown an increase in human cases. Here, we characterize human monoclonal antibodies (mAbs) isolated from a survivor of natural EEEV infection with potent (<20 pM) inhibitory activity of EEEV. Cryo-electron microscopy reconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solved in complex with chimeric Sindbis/EEEV virions to 7.2 Å and 8.3 Å, respectively. The mAbs recognize two distinct antigenic sites that are critical for inhibiting viral entry into cells. EEEV-33 and EEEV-143 protect against disease following stringent lethal aerosol challenge of mice with highly pathogenic EEEV. These studies provide insight into the molecular basis for the neutralizing human antibody response against EEEV and can facilitate development of vaccines and candidate antibody therapeutics.
Identifiants
pubmed: 33301709
pii: S0092-8674(20)31528-2
doi: 10.1016/j.cell.2020.11.011
pmc: PMC7806206
mid: NIHMS1652421
pii:
doi:
Substances chimiques
Aerosols
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Antigens, Viral
0
Epitopes
0
Glycoproteins
0
Recombinant Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1884-1900.e23Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095436
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142790
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL069765
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI145189
Pays : United States
Organisme : NIH HHS
ID : S10 OD021737
Pays : United States
Organisme : NIH HHS
ID : S10 OD020011
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests M.S.D. is consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals, is on the Scientific Advisory Boards of Moderna and Immunome, and is a recipient of grants from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as consultant for Eli Lilly and Sanofi, is on Scientific Advisory Boards of CompuVax and Meissa Vaccines, is recipient of research grants from Moderna and Sanofi, and is Founder of IDBiologics, Inc. Vanderbilt University has applied for patents that are related to this work.