Antibody protects mice from deadly tick-borne virus

In a mouse study, one antibody stood between laboratory animals and a lethal infection with Crimean-Congo hemorrhagic fever virus. Called 9D5, it protected the animals and recognized a part of the virus shared across several strains, giving Scott Pegan's team at the University of California, Riverside, a new route toward a treatment for a disease that can kill up to 40% of infected people.

The target is the virus's nucleocapsid protein, or NP, an internal component that has mainly been used to detect infection rather than treat it. Using X-ray imaging, the researchers mapped how 9D5 binds to the NP's head region. They also identified four antibody-binding areas, spread across the protein's head and stalk, and found that protection was possible whichever region the antibody recognized.

The mechanism is different from the familiar approach of blocking a virus before it enters a cell. NP can appear on the surface of infected cells, the researchers say, allowing antibodies to attach there or to free-floating NP. The material can then be taken inside the cell and interact with TRIM21, an intracellular protein that helps the cell present viral fragments to immune cells capable of clearing the infection.

That matters because Crimean-Congo hemorrhagic fever has no widely approved, highly effective treatment or vaccine. The virus is mainly spread by Hyalomma ticks and can also pass from person to person, especially in health care settings. Pegan's team says changing environmental conditions have helped the ticks expand into new regions, including areas closer to dense populations.

So what changes in practice? Not patient care yet. 9D5 is a mouse antibody, so the team must identify human or humanized versions and test them in preclinical studies and clinical trials. The four binding sites could support antibody cocktails aimed at several parts of the virus or infected cells. Pegan estimates that a treatment could potentially reach patients in about five years, depending on the success of that work.