Researchers identified four distinct antigenic sites on the Crimean-Congo hemorrhagic fever virus nucleocapsid protein using nine monoclonal antibodies, according to a study published in Nature Communications.
Crimean-Congo hemorrhagic fever virus is a tick-borne pathogen endemic across Africa, Asia, and expanding parts of Europe. The virus carries mortality rates approaching 40 percent, exhibits rising incidence, and currently lacks approved medical countermeasures. While the nucleocapsid protein is commonly used for diagnostics, prior work established that antibody 9D5 provides protective efficacy in animal models, establishing the protein as a target for antiviral treatments.
The study localized the four antigenic sites across the head and stalk domains of the nucleocapsid protein. Laboratory evaluations showed variable levels of in vivo protection across the nine tested antibodies. This protection operated independently of whether an antibody targeted the head or stalk domain.
The team solved three X-ray crystallography structures, including the nucleocapsid protein from strain Afg09-2990 bound to antibody 9D5, as well as two unbound protein structures. Structural work used beamline FMX 17-ID-2 at the National Synchrotron Light Source II operated by Brookhaven National Laboratory and the Stanford Synchrotron Radiation Lightsource at SLAC National Accelerator Laboratory. In vivo experiments used interferon alpha/beta receptor knockout mice procured from the Mutant Mouse Resource and Research Centers.
Vanessa Moresco of the University of California Riverside and Aura R. Garrison of the United States Army Medical Research Institute of Infectious Diseases contributed equally as lead authors. Garrison and co-author Joseph W. Golden previously filed U.S. provisional patent application 63/421,704 on November 22, 2022, covering the use of nucleocapsid-targeting antibodies 9D5 and 21B11 against the infection.
