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

• Published in: Nature communications Vol. 13; no. 1; p. 7298
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 631/250/2152/2153/1291; 631/326/596/2557; 631/535/1266; 64/60; 82/1; 82/103; 82/83; Amino acids; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Binding; Crimean hemorrhagic fever; Epitopes; Fever; Glycoproteins; Hemorrhage; Hemorrhagic Fever Virus, Crimean-Congo - chemistry; Hemorrhagic Fever, Crimean - prevention & control; Humanities and Social Sciences; Humans; Infectious diseases; Mice; Monoclonal antibodies; multidisciplinary; Neutralizing; Public health; Science; Science & Technology - Other Topics; Science (multidisciplinary); Strains (organisms); Structural analysis; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34923-0

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. There are currently no approved treatments for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infection. In this study, the authors structurally characterize the epitope targeted by protective non-neutralizing mouse and human antibodies and provide insights into their broad range potential against various CCHFV strains.