Rats lead researchers to a hepatitis C vaccine breakthrough

Researchers at The Rockefeller University and Columbia University have devised an animal model that can be used to study the interaction between hepatitis C and the human body’s immune system. The findings are published in the journal Science.

While hepatitis C can be cured, a vaccine is highly desirable, as many patients do not show outward signs of the disease. More than 80% of those with the virus go undiagnosed.

Charlie Rice, PhD, the Maurice R. and Corinne P. Greenberg Professor in Virology at The Rockefeller University, has been working for decades to develop a vaccine, but his efforts have been stymied by a lack of animal models. Dr Rice’s previous research led to the development of the cure for hepatitis C infection that first became available in 2015.

Recently, Dr. Rice and his colleagues have discovered a method to mimic the disease in rodents using a virus that is closely related to hepatitis C but is able to infect rats and mice. The researchers found that this new animal model is similar to the human disease—a breakthrough that should accelerate research into a viable vaccine.

Hepatitis C is a highly specific virus. It infects only humans and chimpanzees. As such, researchers must rely on blood samples and liver biopsies from infected patients. The samples are limited and infrequent, and they provide only partial information about how the disease progresses and make it difficult to test new vaccines.

"We need to use animals to watch the disease develop over time and monitor how the immune system responds," explains Eva Billerbeck, PhD, a Research Associate in Dr. Rice’s lab and lead author of the new research. "This hasn't been feasible for the hepatitis C virus, which has made our work very difficult."

A breakthrough came in 2014. Ian Lipkin, MD, a Professor at Columbia University discovered a rodent hepacivirus that infected common rats in New York City. The virus is in the same family as hepatitis C. Dr. Lipkin and his colleague Amit Kapoor, PhD, quickly shared the virus with the Rice lab, hoping that it would enable them to create a rodent version of the disease.

Mouse models have a host of genetic tools and techniques that make mechanistic studies possible, so they are the preferred animal model for much of modern biological research. Dr. Rice and his team, including researchers in Copenhagen, investigated whether the rat virus could also infect mice.

They isolated the hepacivirus from rats and successfully exposed standard laboratory mice to the disease. The mice developed a hepacivirus infection that mimicked many of the features of human hepatitis C, with one notable difference.

"In human patients, hepatitis C virus infection has two outcomes," Dr. Billerbeck explains. "Initially, it is acute, and a small percentage of patients fully recover from infection. However, most people progress to a chronic form of the disease that will continue to affect them unless they are treated."

The team found that mice with a healthy immune system have the acute form of the disease and then recover, while immune-compromised animals become chronically infected and remain infected even after their immune systems are restored.

Dr. Rice and his team are now using the new model to see how the body reacts to hepatitis C, and how the infection progresses.

"This research will help unravel mechanisms of liver infection, virus clearance, and disease mechanisms," Dr. Rice says. "[It] should prove valuable as we work to develop and test hepatitis C vaccines that can help to finally eradicate the disease around the world."

To read more about this study, click here.