Ebolavirus Chimerization for the Development of a Mouse Model for Screening of Bundibugyo-Specific Antibodies

Philipp A. Ilinykh; Jessica Graber; Natalia A. Kuzmina; Kai Huang; Thomas G. Ksiazek; James E. Crowe; Alexander Bukreyev

doi:10.1093/infdis/jiy423

Ebolavirus Chimerization for the Development of a Mouse Model for Screening of Bundibugyo-Specific Antibodies

Philipp A. Ilinykh, Jessica Graber, Natalia A. Kuzmina, Kai Huang, Thomas G. Ksiazek, James E. Crowe, Alexander Bukreyev

Pathology

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

2 Scopus citations

Abstract

Screening of monoclonal antibodies against ebolaviruses requires small-animal models. Wild-type mice require adaptation of ebolaviruses, whereas immunodeficient mice are still resistant to nonadapted Bundibugyo ebolavirus. Swapping of Ebola virus glycoprotein with that from Bundibugyo virus resulted in a replication-competent chimeric virus, which caused 100% lethal infection in STAT1 knockout mice. Monoclonal antibody BDBV223 isolated from a human survivor of Bundibugyo virus infection protected mice from challenge with the chimeric virus. These data demonstrate the suitability of the approach for in vivo screening of antibodies and suggest the greater contribution of internal Ebola proteins in pathogenesis compared to Bundibugyo virus proteins.

Original language	English (US)
Pages (from-to)	S418-S422
Journal	Journal of Infectious Diseases
Volume	218
DOIs	https://doi.org/10.1093/infdis/jiy423
State	Published - Nov 22 2018

Keywords

Bundibugyo virus
Ebola virus
glycoprotein
monoclonal antibodies
mouse model

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiy423

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title = "Ebolavirus Chimerization for the Development of a Mouse Model for Screening of Bundibugyo-Specific Antibodies",

abstract = "Screening of monoclonal antibodies against ebolaviruses requires small-animal models. Wild-type mice require adaptation of ebolaviruses, whereas immunodeficient mice are still resistant to nonadapted Bundibugyo ebolavirus. Swapping of Ebola virus glycoprotein with that from Bundibugyo virus resulted in a replication-competent chimeric virus, which caused 100% lethal infection in STAT1 knockout mice. Monoclonal antibody BDBV223 isolated from a human survivor of Bundibugyo virus infection protected mice from challenge with the chimeric virus. These data demonstrate the suitability of the approach for in vivo screening of antibodies and suggest the greater contribution of internal Ebola proteins in pathogenesis compared to Bundibugyo virus proteins.",

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AU - Ilinykh, Philipp A.

AU - Graber, Jessica

AU - Kuzmina, Natalia A.

AU - Huang, Kai

AU - Ksiazek, Thomas G.

AU - Crowe, James E.

AU - Bukreyev, Alexander

PY - 2018/11/22

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AB - Screening of monoclonal antibodies against ebolaviruses requires small-animal models. Wild-type mice require adaptation of ebolaviruses, whereas immunodeficient mice are still resistant to nonadapted Bundibugyo ebolavirus. Swapping of Ebola virus glycoprotein with that from Bundibugyo virus resulted in a replication-competent chimeric virus, which caused 100% lethal infection in STAT1 knockout mice. Monoclonal antibody BDBV223 isolated from a human survivor of Bundibugyo virus infection protected mice from challenge with the chimeric virus. These data demonstrate the suitability of the approach for in vivo screening of antibodies and suggest the greater contribution of internal Ebola proteins in pathogenesis compared to Bundibugyo virus proteins.

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Ebolavirus Chimerization for the Development of a Mouse Model for Screening of Bundibugyo-Specific Antibodies

Abstract

Keywords

ASJC Scopus subject areas

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