Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pntd.0006209
Title: Neutralization of antibody-enhanced dengue infection by VIS513, a pan serotype reactive monoclonal antibody targeting domain III of the dengue E protein
Authors: Budigi Y.
Ong E.Z. 
Robinson L.N.
Ong L.C. 
Rowley K.J.
Winnett A.
Tan H.C. 
Hobbie S.
Shriver Z.
Babcock G.J.
Alonso S. 
Ooi E.E. 
Keywords: dengue E protein
monoclonal antibody
neutralizing antibody
unclassified drug
viral protein
vis513
antiserum
epitope
monoclonal antibody
recombinant protein
virus antibody
virus antigen
virus envelope protein
animal cell
animal experiment
animal model
Article
C6/36 cell line
controlled study
dengue
Dengue virus
Dengue virus 1
Dengue virus 2
Dengue virus 3
Dengue virus 4
female
gene mutation
immobilized metal affinity chromatography
male
mouse
mutational analysis
nonhuman
polymerase chain reaction
reverse transcription polymerase chain reaction
serotype
virus load
virus neutralization
virus strain
animal
blood
cell line
chemistry
Chlorocebus aethiops
cross reaction
dengue
Dengue virus
disease model
genetics
human
immunology
immunotherapy
in vitro study
mutation
pathogenicity
protein conformation
serodiagnosis
structural model
THP-1 cell line
Vero cell line
viral plaque assay
Animals
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
Cell Line
Cercopithecus aethiops
Cross Reactions
Dengue
Dengue Virus
Disease Models, Animal
Epitopes
Female
Humans
Immune Sera
Immunotherapy
In Vitro Techniques
Mice
Models, Structural
Mutation
Neutralization Tests
Protein Conformation
Recombinant Proteins
Serogroup
THP-1 Cells
Vero Cells
Viral Envelope Proteins
Viral Plaque Assay
Issue Date: 2018
Publisher: Public Library of Science
Citation: Budigi Y., Ong E.Z., Robinson L.N., Ong L.C., Rowley K.J., Winnett A., Tan H.C., Hobbie S., Shriver Z., Babcock G.J., Alonso S., Ooi E.E. (2018). Neutralization of antibody-enhanced dengue infection by VIS513, a pan serotype reactive monoclonal antibody targeting domain III of the dengue E protein. PLoS Neglected Tropical Diseases 12 (2) : e0006209. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pntd.0006209
Abstract: Dengue virus (DENV) infection imposes enormous health and economic burden worldwide with no approved treatment. Several small molecules, including lovastatin, celgosivir, balapiravir and chloroquine have been tested for potential anti-dengue activity in clinical trials; none of these have demonstrated a protective effect. Recently, based on identification and characterization of cross-serotype neutralizing antibodies, there is increasing attention on the potential for dengue immunotherapy. Here, we tested the ability of VIS513, an engineered cross-neutralizing humanized antibody targeting the DENV E protein domain III, to overcome antibody-enhanced infection and high but brief viremia, which are commonly encountered in dengue patients, in various in vitro and in vivo models. We observed that VIS513 efficiently neutralizes DENV at clinically relevant viral loads or in the presence of enhancing levels of DENV immune sera. Single therapeutic administration of VIS513 in mouse models of primary infection or lethal secondary antibody-enhanced infection, reduces DENV titers and protects from lethal infection. Finally, VIS513 administration does not readily lead to resistance, either in cell culture systems or in animal models of dengue infection. The findings suggest that rapid viral reduction during acute DENV infection with a monoclonal antibody is feasible. © 2018 Budigi et al.
Source Title: PLoS Neglected Tropical Diseases
URI: https://scholarbank.nus.edu.sg/handle/10635/165622
ISSN: 19352727
DOI: 10.1371/journal.pntd.0006209
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pntd_0006209.pdf6.93 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

3
checked on Sep 26, 2020

Page view(s)

37
checked on Sep 25, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.