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.

doi:10.1038/s41467-022-34923-0

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

Journal Article · Sat Nov 26 00:00:00 EST 2022 · Nature Communications

DOI:https://doi.org/10.1038/s41467-022-34923-0· OSTI ID:2423642

Durie, Ian A. ^[1]; ^[2]; Karaaslan, Elif ^[3]; ^[4]; McGuire, Jack ^[5]; ^[6]; ^[4]; ^[4]; ^[4]; ^[7]; Gonzalez, David ^[5]; Enos, Suzanne ^[1]; Koksal, Iftihar ^[8]; Yilmaz, Gurdal ^[9]; Karakoc, Hanife Nur ^[10]; Hamidi, Sanaz ^[9]; Albay, Cansu ^[9]; ^[4]; Spiropoulou, Christina F. ^[4]; ^[6] more »

Univ. of Georgia, Athens, GA (United States)
Univ. of Maryland, Baltimore, MD (United States). School of Medicine
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Univ. of California, Riverside, CA (United States)
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
Univ. of California, Riverside, CA (United States)
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States)
Univ. of Georgia, Athens, GA (United States). College of Veterinary Medicine
Acibadem University Atakent Hospital, Istanbul (Turkey)
Karadeniz Technical University School of Medicine, Trabzon (Turkey)
Bitlis State Hospital (Turkey)
Univ. of Georgia, Athens, GA (United States); Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
Univ. of California, Riverside, CA (United States); United States Military Academy, West Point, NY (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423642

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 13; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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