Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
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Published:2022-11-26
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Durie Ian A., Tehrani Zahra R.ORCID, Karaaslan Elif, Sorvillo Teresa E.ORCID, McGuire Jack, Golden Joseph W.ORCID, Welch Stephen R.ORCID, Kainulainen Markus H.ORCID, Harmon Jessica R.ORCID, Mousa Jarrod J.ORCID, Gonzalez David, Enos Suzanne, Koksal Iftihar, Yilmaz Gurdal, Karakoc Hanife Nur, Hamidi Sanaz, Albay Cansu, Spengler Jessica R.ORCID, Spiropoulou Christina F., Garrison Aura R.ORCID, Sajadi Mohammad M., Bergeron ÉricORCID, Pegan Scott D.ORCID
Abstract
AbstractCrimean-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.
Funder
Military Infectious Disease Research Program U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases United States Department of Defense | Defense Threat Reduction Agency
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference57 articles.
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