A Cornell researcher is seeking to develop a vaccine against the hepatitis C virus by harnessing the body’s natural ability to clear the infection on its own, thanks to a grant from the Pew Charitable Trusts.
Andrew Flyak, assistant professor in the Department of Microbiology and Immunology in the College of Veterinary Medicine, has been named a 2026 Pew Scholar in the Biomedical Sciences. Flyak is one of 21 Pew Scholars this year to receive a four-year, $300,000 grant.
Andrew Flyak
“The Pew Biomedical Scholars program is an extremely powerful way to support young investigators by providing funding for research that has the potential to change current dogma, and it allows us to push bold projects forward,” Flyak said.
Hepatitis C infects an estimated 70 million people worldwide and causes irreversible liver damage. While an effective antiviral treatment exists, people who are unaware that they carry the virus and intravenous drug users without access to treatment complicate efforts to contain the disease.
“We have a population of people who are infected and spreading the virus,” Flyak said, “so that’s why we believe that in order to control infections, we need to combine treatments with a vaccine.”
Flyak and colleagues came up with the idea for a potential vaccine by investigating how 25% of people infected with hepatitis C virus clear it without any antiviral treatment.
“The immune system can clear the virus but we don’t know how to instruct it to do so reliably,” Flyak said. “The goal is to understand what those individuals’ immune systems are doing, and then replicate it through rational design.”
The hepatitis C virus uses a protein on its surface to bind to a receptor on the host cell. That protein is uniquely flexible and capable of multiple configurations. As a result, vaccine candidates have been hard to develop. Vaccines elicit an immune response in the host by creating antibodies that bind to a virus and block it from binding to host cells, but this becomes a challenge with hepatitis C’s shape-shifting protein, whose binding site becomes a moving target.
Researchers have known that the immune system builds antibodies from a large set of genes. Patients who spontaneously clear the hepatitis C virus had a class of antibodies circulating in their systems encoded by a gene called VH1-69, past studies have shown.
“What is interesting is that we believe these antibodies are themselves structurally plastic,” Flyak said. “We’re proposing to fight fire with fire. We believe that the immune system uses flexible VH1-69 antibodies to bind to a flexible part of the viral protein.”
The Pew grant will allow the team to use electron microscopy, X-ray crystallography, and molecular simulations to understand how VH1-69 antibodies are so good at neutralizing the hepatitis C virus. The researchers also plan to use generative artificial intelligence to help design vaccine candidates.
“The long-term vision is that this could be a general framework for designing vaccines against any target that is genetically diverse and flexible, including proteins involved in cancer,” Flyak said.
Flyak received a bachelor’s degree from Taras Shevchenko National University of Kyiv, Ukraine (2009) and a doctorate from Vanderbilt University (2016). Prior to joining Cornell in 2022, he was a postdoctoral researcher at the California Institute of Technology.
