Rodents Provide Possible Breakthrough Toward Hepatitis C Vaccine

New research may pave the way for a hepatitis C virus (HCV) vaccination, thanks to a method developed to mimic the liver-attacking disease in rodents.

Until now, the search for an HCV vaccine has been hampered by a lack of animal models to study the interaction between the virus and the immune system, according to research from New York City-based Rockefeller University.

“It is not possible to model all aspects of this complex host-virus interaction with cell culture models,’’ Charles M. Rice (pictured), PhD, a virology professor at the university, said.

An “in-vivo model with an intact immune system” is necessary to understand and probe pathogenesis of HCV and similar viruses, Rice said.

To accomplish that goal, researchers in Rice’s lab injected four-week old mice with a version of HCV that had previously been identified in New York City rats. The hepacivirus, (Norway rat hepacivirus, NrHV) mimicked immunological features similar to those seen in human viral hepatitis, according to the team.

Unlike HCV in people, the researchers discovered that mice with a healthy immune system experience the acute form of the disease and then recover. In addition, mice infected with varying amounts of the virus cleared it with similar kinetics.

Most humans, in contrast, progress to a chronic form of HCV that will continue to affect them unless they’re treated.

While today’s direct-acting antiviral (DAA) drugs can produce close to universal cure rates, developing a vaccine is key to eliminating the disease worldwide, Rice said.

“While we have effective treatments that can cure the virus in most of those treated, cost and other aspects of implementing these advances are slow and often difficult in high risk groups,” Rice said. “Even ardent therapy fans admit that a vaccine that prevents chronic infection would be useful in efforts to control and eliminate this virus on a global scale.”

The researchers are using their new animal models to gain insight into how HCV infection progresses and to understand how the body reacts.

“‘We plan to test various vaccine and immunomodulatory platforms in the contact of acute and chronic infection,” Rice said.

The team is especially interested in possible parallels in treating cancer.

“The chronic infection model is particularly intriguing given that the inability of the immune system to eliminate the virus in many ways mimics the situation with cancer,” Rice said. “Understanding how to stimulate a “stunned" immune system to recognize foreign antigens has implications not only for chronic viral infection but also cancer immunotherapy.”

The study, “Mouse models of acute and chronic hepacivirus infection,” was published online in the journal Science last month.

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