Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap

Philipp A. Ilinykh, Rodrigo I. Santos, Bronwyn M. Gunn, Natalia A. Kuzmina, Xiaoli Shen, Kai Huang, Pavlo Gilchuk, Andrew I. Flyak, Patrick Younan, Galit Alter, James E. Crowe, Alexander Bukreyev

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recent studies suggest that some monoclonal antibodies (mAbs) specific for ebolavirus glycoprotein (GP) can protect experimental animals against infections. Most mAbs isolated from ebolavirus survivors appeared to target the glycan cap or the stalk region of the viral GP, which is the envelope protein and the only antigen inducing virus-neutralizing antibody response. Some of the mAbs were demonstrated to be protective in vivo. Here, a panel of mAbs from four individual survivors of ebolavirus infection that target the glycan cap or stem region were selected for investigation of the mechanisms of their antiviral effect. Comparative characterization of the inhibiting effects on multiple steps of viral replication was performed, including attachment, post-attachment, entry, binding at low pH, post-cleavage neutralization of virions, viral trafficking to endosomes, cell-to-cell transmission, viral egress, and inhibition when added early at various time points post-infection. In addition, Fc-domain related properties were characterized, including activation and degranulation of NK cells, antibody-dependent cellular phagocytosis and glycan content. The two groups of mAbs (glycan cap versus stem) demonstrated very different profiles of activities suggesting usage of mAbs with different epitope specificity could coordinate inhibition of multiple steps of filovirus infection through Fab- and Fc-mediated mechanisms, and provide a reliable therapeutic approach.

Original languageEnglish (US)
Article numbere1007204
JournalPLoS Pathogens
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Ebolavirus
Antiviral Agents
Polysaccharides
Glycoproteins
Monoclonal Antibodies
Antibodies
Infection
Endosomes
Neutralizing Antibodies
Phagocytosis
Natural Killer Cells
Virion
Antibody Formation
Epitopes
Viruses
Antigens

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap. / Ilinykh, Philipp A.; Santos, Rodrigo I.; Gunn, Bronwyn M.; Kuzmina, Natalia A.; Shen, Xiaoli; Huang, Kai; Gilchuk, Pavlo; Flyak, Andrew I.; Younan, Patrick; Alter, Galit; Crowe, James E.; Bukreyev, Alexander.

In: PLoS Pathogens, Vol. 14, No. 8, e1007204, 01.08.2018.

Research output: Contribution to journalArticle

Ilinykh, PA, Santos, RI, Gunn, BM, Kuzmina, NA, Shen, X, Huang, K, Gilchuk, P, Flyak, AI, Younan, P, Alter, G, Crowe, JE & Bukreyev, A 2018, 'Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap', PLoS Pathogens, vol. 14, no. 8, e1007204. https://doi.org/10.1371/journal.ppat.1007204
Ilinykh, Philipp A. ; Santos, Rodrigo I. ; Gunn, Bronwyn M. ; Kuzmina, Natalia A. ; Shen, Xiaoli ; Huang, Kai ; Gilchuk, Pavlo ; Flyak, Andrew I. ; Younan, Patrick ; Alter, Galit ; Crowe, James E. ; Bukreyev, Alexander. / Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap. In: PLoS Pathogens. 2018 ; Vol. 14, No. 8.
@article{1e1d7b0f6ce644f588ac2e4ac8c110cd,
title = "Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap",
abstract = "Recent studies suggest that some monoclonal antibodies (mAbs) specific for ebolavirus glycoprotein (GP) can protect experimental animals against infections. Most mAbs isolated from ebolavirus survivors appeared to target the glycan cap or the stalk region of the viral GP, which is the envelope protein and the only antigen inducing virus-neutralizing antibody response. Some of the mAbs were demonstrated to be protective in vivo. Here, a panel of mAbs from four individual survivors of ebolavirus infection that target the glycan cap or stem region were selected for investigation of the mechanisms of their antiviral effect. Comparative characterization of the inhibiting effects on multiple steps of viral replication was performed, including attachment, post-attachment, entry, binding at low pH, post-cleavage neutralization of virions, viral trafficking to endosomes, cell-to-cell transmission, viral egress, and inhibition when added early at various time points post-infection. In addition, Fc-domain related properties were characterized, including activation and degranulation of NK cells, antibody-dependent cellular phagocytosis and glycan content. The two groups of mAbs (glycan cap versus stem) demonstrated very different profiles of activities suggesting usage of mAbs with different epitope specificity could coordinate inhibition of multiple steps of filovirus infection through Fab- and Fc-mediated mechanisms, and provide a reliable therapeutic approach.",
author = "Ilinykh, {Philipp A.} and Santos, {Rodrigo I.} and Gunn, {Bronwyn M.} and Kuzmina, {Natalia A.} and Xiaoli Shen and Kai Huang and Pavlo Gilchuk and Flyak, {Andrew I.} and Patrick Younan and Galit Alter and Crowe, {James E.} and Alexander Bukreyev",
year = "2018",
month = "8",
day = "1",
doi = "10.1371/journal.ppat.1007204",
language = "English (US)",
volume = "14",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap

AU - Ilinykh, Philipp A.

AU - Santos, Rodrigo I.

AU - Gunn, Bronwyn M.

AU - Kuzmina, Natalia A.

AU - Shen, Xiaoli

AU - Huang, Kai

AU - Gilchuk, Pavlo

AU - Flyak, Andrew I.

AU - Younan, Patrick

AU - Alter, Galit

AU - Crowe, James E.

AU - Bukreyev, Alexander

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Recent studies suggest that some monoclonal antibodies (mAbs) specific for ebolavirus glycoprotein (GP) can protect experimental animals against infections. Most mAbs isolated from ebolavirus survivors appeared to target the glycan cap or the stalk region of the viral GP, which is the envelope protein and the only antigen inducing virus-neutralizing antibody response. Some of the mAbs were demonstrated to be protective in vivo. Here, a panel of mAbs from four individual survivors of ebolavirus infection that target the glycan cap or stem region were selected for investigation of the mechanisms of their antiviral effect. Comparative characterization of the inhibiting effects on multiple steps of viral replication was performed, including attachment, post-attachment, entry, binding at low pH, post-cleavage neutralization of virions, viral trafficking to endosomes, cell-to-cell transmission, viral egress, and inhibition when added early at various time points post-infection. In addition, Fc-domain related properties were characterized, including activation and degranulation of NK cells, antibody-dependent cellular phagocytosis and glycan content. The two groups of mAbs (glycan cap versus stem) demonstrated very different profiles of activities suggesting usage of mAbs with different epitope specificity could coordinate inhibition of multiple steps of filovirus infection through Fab- and Fc-mediated mechanisms, and provide a reliable therapeutic approach.

AB - Recent studies suggest that some monoclonal antibodies (mAbs) specific for ebolavirus glycoprotein (GP) can protect experimental animals against infections. Most mAbs isolated from ebolavirus survivors appeared to target the glycan cap or the stalk region of the viral GP, which is the envelope protein and the only antigen inducing virus-neutralizing antibody response. Some of the mAbs were demonstrated to be protective in vivo. Here, a panel of mAbs from four individual survivors of ebolavirus infection that target the glycan cap or stem region were selected for investigation of the mechanisms of their antiviral effect. Comparative characterization of the inhibiting effects on multiple steps of viral replication was performed, including attachment, post-attachment, entry, binding at low pH, post-cleavage neutralization of virions, viral trafficking to endosomes, cell-to-cell transmission, viral egress, and inhibition when added early at various time points post-infection. In addition, Fc-domain related properties were characterized, including activation and degranulation of NK cells, antibody-dependent cellular phagocytosis and glycan content. The two groups of mAbs (glycan cap versus stem) demonstrated very different profiles of activities suggesting usage of mAbs with different epitope specificity could coordinate inhibition of multiple steps of filovirus infection through Fab- and Fc-mediated mechanisms, and provide a reliable therapeutic approach.

UR - http://www.scopus.com/inward/record.url?scp=85053077471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053077471&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1007204

DO - 10.1371/journal.ppat.1007204

M3 - Article

VL - 14

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1007204

ER -