June 1, 2021—(BRONX, NY)—An international consortium of investigators in academia, industry, and government, led and coordinated by Albert Einstein College of Medicine scientists, has developed a monoclonal antibody-based therapy against Crimean-Congo hemorrhagic fever virus (CCHFV), a highly virulent tick-borne pathogen affecting eastern and southern Europe, Africa, the Middle East, India, and Central Asia. Up to 40% of CCHFV cases prove fatal and there are currently no treatments or vaccines. The drug was tested in mice and the results were described in a new study published online today in Cell.
In 2019, the consortium—the Prometheus Center for Excellence in Translational Research (Prometheus)—was awarded a five-year, $22 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to develop antibody-based therapies against CCHFV and three other highly lethal viruses for which there are no approved vaccines or treatments. Kartik Chandran, Ph.D., professor of microbiology & immunology and the Harold and Muriel Block Faculty Scholar in Virology at Einstein, is the principal investigator on the Prometheus grant. The high virulence of CCHFV, the increased frequency of outbreaks, and the continued expansion of its geographical reach have led the World Health Organization to prioritize research for treatments.
Although belonging to a different family of viruses, CCHFV bears some similarities to the coronavirus that causes COVID-19. The surfaces of both viruses contain spike glycoproteins used to infect human and animal cells, and infections trigger the immune system to produce antibodies that primarily target the spike glycoproteins. Using the CCHFV spike glycoprotein as “bait,” the Prometheus team fished for antibodies in blood donated by four Ugandan survivors of CCHFV infection. They discovered more than 350 different antibodies that target different parts of the CCHFV spike and screened them to identify antibodies that potently neutralized CCHFV infection.
The team paired up the most potent monoclonal antibodies to form bispecific antibodies: synthetic antibodies with two “business ends” that can bind to two different parts of CCHFV’s spike glycoprotein at the same time. A single dose of one of these bispecific antibodies protected mice from a lethal dose of CCHFV even when the therapy was administered 24 hours after the animals were infected.
Our international team was able to leverage our multidisciplinary strengths in basic science, engineering, and drug discovery to create antibody-based compounds with the potential to defeat an emerging and lethal infection.
Kartik Chandran, Ph.D.
“Our international team was able to leverage our multidisciplinary strengths in basic science, engineering, and drug discovery to create antibody-based compounds with the potential to defeat an emerging and lethal infection,” said Dr. Chandran. “The next step is to shepherd this through the drug-development process, which we hope will lead to a life-saving therapy for people infected by CCHFV.”
Other institutions participating in this Prometheus project were: Adimab, LLC; the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID); Mapp Biopharmaceutical, Inc.; the University of Texas Medical Branch at Galveston; the University of Texas at Austin; Institut Pasteur in Paris, France; Ben-Gurion University of the Negev in Beer-Sheva, Israel; and Uganda Virus Research Institute in Entebbe, Uganda. Laura M. Walker, Ph.D. (Adimab), John M. Dye, Ph.D. (USAMRIID), and Zachary A. Bornholdt, Ph.D. (Mapp) are co-senior authors together with Dr. Chandran. J. Maximilian Fels, Ph.D. (Einstein), Daniel Maurer (Adimab), and Andrew S. Herbert, Ph.D. (USAMRIID) are co-first authors. Additional Einstein authors include: Ariel S. Wirchnianski, Olivia Vergnolle, Ph.D., Jennifer Aguilan, Ph.D., Gregory Quevedo, Simone Sidoli, Ph.D., and Jonathan R. Lai, Ph.D. The paper is titled “Protective neutralizing antibodies from human survivors of Crimean-Congo hemorrhagic fever.” The NIAID grant (U19 AI142777) is titled Prometheus: A Platform for Rapid Development of Human Antibody-based Therapeutics and Prophylactics against Emerging Viral Threats.