Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. T...

Full description

Bibliographic Details
Main Authors: Benjamin Gutjahr, Markus Keller, Melanie Rissmann, Felicitas von Arnim, Susanne Jäckel, Sven Reiche, Reiner Ulrich, Martin H Groschup, Martin Eiden
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-03-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0008143
id doaj-8fa9ac3b6c004272ba698ed98c42a5d2
record_format Article
spelling doaj-8fa9ac3b6c004272ba698ed98c42a5d22021-03-03T07:54:57ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-03-01143e000814310.1371/journal.pntd.0008143Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.Benjamin GutjahrMarkus KellerMelanie RissmannFelicitas von ArnimSusanne JäckelSven ReicheReiner UlrichMartin H GroschupMartin EidenRift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.https://doi.org/10.1371/journal.pntd.0008143
collection DOAJ
language English
format Article
sources DOAJ
author Benjamin Gutjahr
Markus Keller
Melanie Rissmann
Felicitas von Arnim
Susanne Jäckel
Sven Reiche
Reiner Ulrich
Martin H Groschup
Martin Eiden
spellingShingle Benjamin Gutjahr
Markus Keller
Melanie Rissmann
Felicitas von Arnim
Susanne Jäckel
Sven Reiche
Reiner Ulrich
Martin H Groschup
Martin Eiden
Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
PLoS Neglected Tropical Diseases
author_facet Benjamin Gutjahr
Markus Keller
Melanie Rissmann
Felicitas von Arnim
Susanne Jäckel
Sven Reiche
Reiner Ulrich
Martin H Groschup
Martin Eiden
author_sort Benjamin Gutjahr
title Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
title_short Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
title_full Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
title_fullStr Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
title_full_unstemmed Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
title_sort two monoclonal antibodies against glycoprotein gn protect mice from rift valley fever challenge by cooperative effects.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2020-03-01
description Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.
url https://doi.org/10.1371/journal.pntd.0008143
work_keys_str_mv AT benjamingutjahr twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT markuskeller twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT melanierissmann twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT felicitasvonarnim twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT susannejackel twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT svenreiche twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT reinerulrich twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT martinhgroschup twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
AT martineiden twomonoclonalantibodiesagainstglycoproteingnprotectmicefromriftvalleyfeverchallengebycooperativeeffects
_version_ 1714827028609368064