Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 26, 2022
- Source ID
- 10.1038/s41467-022-34923-0
Entities
People
- Aura Garrison
- Cansu Albay
- Christina F Spiropoulou
- David Gonzalez
- Elif Karaaslan
- Eric Bergeron
- Gurdal Yilmaz
- Hanife Nur Karakoc
- Ian A. Durie
- Iftihar Koksal
- Jack Mcguire
- Jarrod J. Mousa
- Jessica R Harmon
- Jessica R. Spengler
- Joseph W. Golden
- Markus H. Kainulainen
- Mohammad M Sajadi
- Sanaz Hamidi
- Scott D Pegan
- Stephen R Welch
- Suzanne Enos
- Teresa E Sorvillo
- Zahra Rikhtegaran Tehrani
Organizations
- Defense Threat Reduction Agency
- National Institute of Allergy and Infectious Diseases
- United States Department of Health and Human Services