Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

Caleb D. Marceau; Surendra S. Negi; Humberto Hernandez; Julie Callison; Andrea Marzi; Viktoriya Borisevich; Werner Braun; Jody Berry; Heinz Feldmann; Barry Rockx

doi:10.1016/j.trivac.2014.04.002

Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

Caleb D. Marceau, Surendra S. Negi, Humberto Hernandez, Julie Callison, Andrea Marzi, Viktoriya Borisevich, Werner Braun, Jody Berry, Heinz Feldmann, Barry Rockx

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP). The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV) glycoprotein (GP) has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs), termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV), respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP₁ subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

Original language	English (US)
Pages (from-to)	89-94
Number of pages	6
Journal	Trials in Vaccinology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.trivac.2014.04.002
State	Published - 2014
Externally published	Yes

Keywords

Animal model
Filovirus
Neutralizing antibody
Prophylaxis

ASJC Scopus subject areas

Microbiology
Immunology
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.trivac.2014.04.002

Cite this

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title = "Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges",

abstract = "Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP). The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV) glycoprotein (GP) has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs), termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV), respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.",

keywords = "Animal model, Filovirus, Neutralizing antibody, Prophylaxis",

author = "Marceau, {Caleb D.} and Negi, {Surendra S.} and Humberto Hernandez and Julie Callison and Andrea Marzi and Viktoriya Borisevich and Werner Braun and Jody Berry and Heinz Feldmann and Barry Rockx",

note = "Funding Information: This work was supported by start-up funds from the Department of Pathology and Institute for Human Infections and Immunity at UTMB to B.R. and the Intramural Research Program of the NIAID, NIH. Funding Information: We{\textquoteright}d like the thank Robyn Cassan, Marelle Montanez, Bethany Tiner and Tierra Farris for technical assistance. The study was financially supported through start-up funds from the Department of Pathology and the Institute of Human Infections and Immunity, UTMB to B.R. and by the Intramural Research Program of the NIAID, NIH .",

year = "2014",

doi = "10.1016/j.trivac.2014.04.002",

language = "English (US)",

volume = "3",

pages = "89--94",

journal = "Trials in Vaccinology",

issn = "1879-4378",

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T1 - Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

AU - Marceau, Caleb D.

AU - Negi, Surendra S.

AU - Hernandez, Humberto

AU - Callison, Julie

AU - Marzi, Andrea

AU - Borisevich, Viktoriya

AU - Braun, Werner

AU - Berry, Jody

AU - Feldmann, Heinz

AU - Rockx, Barry

N1 - Funding Information: This work was supported by start-up funds from the Department of Pathology and Institute for Human Infections and Immunity at UTMB to B.R. and the Intramural Research Program of the NIAID, NIH. Funding Information: We’d like the thank Robyn Cassan, Marelle Montanez, Bethany Tiner and Tierra Farris for technical assistance. The study was financially supported through start-up funds from the Department of Pathology and the Institute of Human Infections and Immunity, UTMB to B.R. and by the Intramural Research Program of the NIAID, NIH .

PY - 2014

Y1 - 2014

N2 - Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP). The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV) glycoprotein (GP) has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs), termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV), respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

AB - Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP). The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV) glycoprotein (GP) has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs), termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV), respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

KW - Animal model

KW - Filovirus

KW - Neutralizing antibody

KW - Prophylaxis

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JO - Trials in Vaccinology

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ER -

Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

Abstract

Keywords

ASJC Scopus subject areas

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