Researchers identified a viral protein as a target for antiviral and vaccine development, as well as an antibody that might benefit the immunocompromised.
Epstein-Barr Virus (EBV) is one of the most common human viruses in the world. It is the major cause of infectious mononucleosis and is associated with approximately 200,000 new cases of cancer every year. And people infected with EBV, according to a recent study, might be more likely to develop multiple sclerosis, a debilitating neurological disease. Given the potential impacts on human health, research into the treatment and prevention of EBV is of great importance.
A team that includes researchers from the National Institutes of Health (NIH) and the Walter Reed Army Institute of Research has made a critical discovery in the race to find effective EBV antibody treatments and vaccines. With the aid of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory, the researchers were able to examine the structures of the virus’s proteins along with antibodies.
The APS, one of the most productive X-ray light sources in the world, allowed them to identify a specific protein found on the viral cell’s surface, known as a glycoprotein, as a target for antiviral and vaccine development. Results of the research were published in the journal Immunity.
“With Argonne’s help, we were able to figure out at the atomic level exactly how those antibodies bind to the glycoprotein.” — Jeffrey Cohen, chief of the Laboratory of Infectious Diseases at the National Institutes of Health
The researchers also identified six potent neutralizing monoclonal antibodies, which were isolated from blood donors who displayed high levels of antibodies to combat EBV. These antibodies fight off infection and are typically administered to high-risk patients intravenously in order to attack viruses and prevent them from invading cells. At Argonne, using a method called X-ray crystallography, the researchers aimed a high-intensity X-ray beam at lab-generated crystals of the antibodies bound to five distinct sites on one of the EBV’s glycoproteins. They were then able to inspect the bonds formed between them.
“With Argonne’s help, we were able to figure out at the atomic level exactly how those antibodies bind to the glycoprotein,” said Jeffrey Cohen, chief of the Laboratory of Infectious Diseases at NIH and a principal investigator in the study. “Knowing which are the critical regions of the protein becomes very important in developing antibody therapy and designing vaccines.”
One of the monoclonal antibodies, the researchers found, provided near complete protection against viral infection and lymphatic cancers in laboratory tests with “humanized” mice engineered to have a human immune system.
“If we give EBV to normal humanized mice, half of those mice will get EBV lymphomas,” Cohen explained. “But if we give one of the monoclonal antibodies to the humanized mice and challenge them with EBV, almost none of them developed lymphomas.”
Those experiments allowed the researchers to conclude that the antibody might be useful to give to people who are immunocompromised and at a high risk of developing EBV lymphomas, including recipients of organ and bone marrow transplants.
“We wouldn’t be working with X-ray crystallographers if we didn’t think it was important for patients,” Cohen said. “Argonne’s APS has been incredibly helpful in moving research into EBV antibodies and vaccines further along.”
The work was performed at the Southeast Regional Collaborative Access Team beamline at the APS, operated by the University of Georgia, and the Northeastern Collaborative Access Team (NE-CAT) beamline, which is managed by Cornell University.
“It’s gratifying to be able to play a role in helping make these discoveries possible,” said Frank Murphy, co-director of NE-CAT. “This kind of research is only possible at a facility with the capabilities of the APS, and it shows why the APS is critical scientific infrastructure for human health.”
About the Advanced Photon Source
The U. S. Department of Energy Office of Science’s Advanced Photon Source (APS) at Argonne National Laboratory is one of the world’s most productive X-ray light source facilities. The APS provides high-brightness X-ray beams to a diverse community of researchers in materials science, chemistry, condensed matter physics, the life and environmental sciences, and applied research. These X-rays are ideally suited for explorations of materials and biological structures; elemental distribution; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injector sprays, all of which are the foundations of our nation’s economic, technological, and physical well-being. Each year, more than 5,000 researchers use the APS to produce over 2,000 publications detailing impactful discoveries, and solve more vital biological protein structures than users of any other X-ray light source research facility. APS scientists and engineers innovate technology that is at the heart of advancing accelerator and light-source operations. This includes the insertion devices that produce extreme-brightness X-rays prized by researchers, lenses that focus the X-rays down to a few nanometers, instrumentation that maximizes the way the X-rays interact with samples being studied, and software that gathers and manages the massive quantity of data resulting from discovery research at the APS.
This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.
The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.
