Challenges Developing a Hepatitis C Vaccine

Segment Description: Andrea L. Cox, MD, PhD, Professor of Medicine at Johns Hopkins University, discusses some of the challenges in developing a vaccine for hepatitis C and details the results of a vaccine trial.

Interview Transcript (modified slightly for readability):

Cox: Because hepatitis C doesn't replicate well in culture, including in animal cells, it's very difficult to make a live-attenuated or even a killed vaccine. So, the strategy employed here was to use viral vectors, specifically chimpanzee adenovirus 3 and modified vaccinia ankara, not capable of replicating but encoding Hepatitis C virus nonstructural proteins.

The point of the vaccine was to induce robust T cell responses not neutralizing antibodies because the envelope component of the virus isn't in the vaccine. And that was the strategy employed. The first vaccine was the chimpanzee adenovirus 3 given initially or placebo.

Then 8 weeks later, the second dose of placebo or the modified vaccinia Ankara, both chimpanzee adenovirus and modified vaccinia ankara, encoding the nonstructural proteins of Hep C.

This is the first ever trial that could look at efficacy of a Hepatitis C virus vaccine. We've not attempted in the past to test any vaccine against hepatitis C to see if it could modulate the course of disease.

Because the vaccine didn't contain envelope and wasn't predicted to induce neutralizing antibodies or reduce incidence, the primary outcome was to look at a reduction in the development of chronic infection. It's really chronic infection that mediates the vast majority, almost all, disease from hepatitis C. And the idea was that if we could reduce the risk upon exposure of the development of chronic infection that would have a big impact both on transmission of disease because people wouldn't remain persistently infected, and also would reduce the likelihood of developing disease at later stages.

The vaccines were well tolerated and did induce T cell responses, although less robustly then in healthy volunteers. The vaccine trial took place in people who are actively injecting drugs, and we're not certain if that patient population or other factors led to the slightly less robust responses seen, but in the end, there was a blunting of peak HCV RNA by about six-fold in vaccinees. We saw lower geometric mean peak HCV RNA levels, but finally, that did not result in either a reduction of incidence or in progression to chronic infection.