Crimean-Congo hemorrhagic fever virus (CCHFV), a highly lethal tickborne disease, kills up to 40% of people it infects. Those infections occur through tick bites or by handling the carcasses of infected sheep, goats, and cattle. No vaccines or drugs are available for preventing or treating the disease, which causes increasingly frequent and widespread hemorrhagic-fever outbreaks in Africa, Europe, and Asia. Infected cells release the viral glycoprotein GP38, considered a promising target for protective vaccines and antibodies because antibodies specific for GP38 protect against severe disease in animal models. But a lack of knowledge about GP38—what it does and why blocking it is protective—has hampered efforts to develop countermeasures.

Now, research led by Kartik Chandran, Ph.D., Eva Harris, Ph.D., of the University of California-Berkeley, and Andrew Herbert, Ph.D., of the U.S. Army Medical Research Institute of Infectious Diseases has yielded insights into why GP38 is a good antiviral target. Using a mouse model, the scientists found that CCHFV infection—as well as GP38 alone—causes blood to leak from blood vessels, allowing the virus to spread to organs such as the liver and spleen where it can multiply. Using a panel of monoclonal antibodies targeting different regions of GP38, the researchers identified the most effective antibodies in protecting mice against lethal CCHFV challenge. The findings emphasize the importance of including GP38 in designing CCHFV vaccines and provide a starting point for rationally designing antibodies for anti-CCHFV therapy. The results were published online on February 19 in Science Translational Medicine—the first publication from the PROVIDENT consortium, a multi-institute, National Institutes of Health-supported collaboration aimed at developing vaccines and treatments against CCHFV and other viral threats.

Dr. Chandran is professor of microbiology & immunology, the Gertrude and David Feinson Chair in Medicine, and the Harold and the Muriel Block Faculty Scholar in Virology at Einstein.