Chimeric Filoviruses for Identification and Characterization of Monoclonal Antibodies

Journal of Virology
Philipp A IlinykhAlexander Bukreyev

Abstract

Recent experiments suggest that some glycoprotein (GP)-specific monoclonal antibodies (MAbs) can protect experimental animals against the filovirus Ebola virus (EBOV). There is a need for isolation of MAbs capable of neutralizing multiple filoviruses. Antibody neutralization assays for filoviruses frequently use surrogate systems such as the rhabdovirus vesicular stomatitis Indiana virus (VSV), lentiviruses or gammaretroviruses with their envelope proteins replaced with EBOV GP or pseudotyped with EBOV GP. It is optimal for both screening and in-depth characterization of newly identified neutralizing MAbs to generate recombinant filoviruses that express a reporter fluorescent protein in order to more easily monitor and quantify the infection. Our study showed that unlike neutralization-sensitive chimeric VSV, authentic filoviruses are highly resistant to neutralization by MAbs. We used reverse genetics techniques to replace EBOV GP with its counterpart from the heterologous filoviruses Bundibugyo virus (BDBV), Sudan virus, and even Marburg virus and Lloviu virus, which belong to the heterologous genera in the filovirus family. This work resulted in generation of multiple chimeric filoviruses, demonstrating the ability of filovi...Continue Reading

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Citations

Jun 9, 2016·FEMS Microbiology Reviews·Robin BurkJens H Kuhn
Aug 24, 2018·PLoS Pathogens·Philipp A IlinykhAlexander Bukreyev
Apr 25, 2019·The Journal of General Virology·Lennart KämperThomas Hoenen
Mar 6, 2019·Nature Structural & Molecular Biology·Brandyn R WestErica Ollmann Saphire
Apr 19, 2019·Nature Communications·Liam B KingErica Ollmann Saphire
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Nina G BozhanovaJens Meiler
Mar 27, 2021·Nature Communications·Robert W CrossThomas W Geisbert
Jun 28, 2021·The Lancet Infectious Diseases·Philipp A Ilinykh, Alexander Bukreyev

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