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Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and...

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Autores principales: Durie, Ian A., Tehrani, Zahra R., Karaaslan, Elif, Sorvillo, Teresa E., McGuire, Jack, Golden, Joseph W., Welch, Stephen R., Kainulainen, Markus H., Harmon, Jessica R., Mousa, Jarrod J., Gonzalez, David, Enos, Suzanne, Koksal, Iftihar, Yilmaz, Gurdal, Karakoc, Hanife Nur, Hamidi, Sanaz, Albay, Cansu, Spengler, Jessica R., Spiropoulou, Christina F., Garrison, Aura R., Sajadi, Mohammad M., Bergeron, Éric, Pegan, Scott D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701186/
https://www.ncbi.nlm.nih.gov/pubmed/36435827
http://dx.doi.org/10.1038/s41467-022-34923-0
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author Durie, Ian A.
Tehrani, Zahra R.
Karaaslan, Elif
Sorvillo, Teresa E.
McGuire, Jack
Golden, Joseph W.
Welch, Stephen R.
Kainulainen, Markus H.
Harmon, Jessica R.
Mousa, Jarrod J.
Gonzalez, David
Enos, Suzanne
Koksal, Iftihar
Yilmaz, Gurdal
Karakoc, Hanife Nur
Hamidi, Sanaz
Albay, Cansu
Spengler, Jessica R.
Spiropoulou, Christina F.
Garrison, Aura R.
Sajadi, Mohammad M.
Bergeron, Éric
Pegan, Scott D.
author_facet Durie, Ian A.
Tehrani, Zahra R.
Karaaslan, Elif
Sorvillo, Teresa E.
McGuire, Jack
Golden, Joseph W.
Welch, Stephen R.
Kainulainen, Markus H.
Harmon, Jessica R.
Mousa, Jarrod J.
Gonzalez, David
Enos, Suzanne
Koksal, Iftihar
Yilmaz, Gurdal
Karakoc, Hanife Nur
Hamidi, Sanaz
Albay, Cansu
Spengler, Jessica R.
Spiropoulou, Christina F.
Garrison, Aura R.
Sajadi, Mohammad M.
Bergeron, Éric
Pegan, Scott D.
author_sort Durie, Ian A.
collection PubMed
description Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.
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spelling pubmed-97011862022-11-28 Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus Durie, Ian A. Tehrani, Zahra R. Karaaslan, Elif Sorvillo, Teresa E. McGuire, Jack Golden, Joseph W. Welch, Stephen R. Kainulainen, Markus H. Harmon, Jessica R. Mousa, Jarrod J. Gonzalez, David Enos, Suzanne Koksal, Iftihar Yilmaz, Gurdal Karakoc, Hanife Nur Hamidi, Sanaz Albay, Cansu Spengler, Jessica R. Spiropoulou, Christina F. Garrison, Aura R. Sajadi, Mohammad M. Bergeron, Éric Pegan, Scott D. Nat Commun Article Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains. Nature Publishing Group UK 2022-11-26 /pmc/articles/PMC9701186/ /pubmed/36435827 http://dx.doi.org/10.1038/s41467-022-34923-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Durie, Ian A.
Tehrani, Zahra R.
Karaaslan, Elif
Sorvillo, Teresa E.
McGuire, Jack
Golden, Joseph W.
Welch, Stephen R.
Kainulainen, Markus H.
Harmon, Jessica R.
Mousa, Jarrod J.
Gonzalez, David
Enos, Suzanne
Koksal, Iftihar
Yilmaz, Gurdal
Karakoc, Hanife Nur
Hamidi, Sanaz
Albay, Cansu
Spengler, Jessica R.
Spiropoulou, Christina F.
Garrison, Aura R.
Sajadi, Mohammad M.
Bergeron, Éric
Pegan, Scott D.
Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title_full Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title_fullStr Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title_full_unstemmed Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title_short Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
title_sort structural characterization of protective non-neutralizing antibodies targeting crimean-congo hemorrhagic fever virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701186/
https://www.ncbi.nlm.nih.gov/pubmed/36435827
http://dx.doi.org/10.1038/s41467-022-34923-0
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