Dr Ellie Barnes aims to develop a prophylactic and a therapeutic hepatitis C virus vaccine to combat a global epidemic currently infecting 170 million people worldwide. Many chronically infected patients silently develop complications of liver disease that can include hepatocellular cancer, liver cirrhosis and liver failure.
Inducing an antibody reaction to Hepatitis C does not work as it does in other vaccines as the antibodies target the outer surface of the Hepatitis C virus, which is very variable. Therefore efforts are being made to develop a vaccine which induces the T cell arm of the immune response, targeting the virus more effectively.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: Why do we need a vaccine against Hepatitis C?
EB: Hepatitis C is a massive problem worldwide; the World Health Organisation has estimated that there are 170 million people infected worldwide. In some parts of the world it is as high as 10% or 20% of the population, for example in parts of Asia. Here in the United Kingdom 0.5% of the population - that is 300,000 people - have Hepatitis C. And once you are infected, some people live with their virus without any problems but in others the virus over many years causes liver scarring, eventually liver cirrhosis, liver cancer and liver failure. It is actually one of the leading causes now for liver transplantation in the UK so obviously a vaccine that could prevent all that from happening would be a fantastic clinical asset.
Q: And why is it proving difficult to develop a vaccine?
EB: All the vaccines which we currently have that work, they work through inducing an antibody response, inducing the antibody arm of the immune response. The problem with Hepatitis C is that approach on its own is unlikely to work, and the reason is that the antibodies target the outer surface of the Hepatitis C virus which is very variable. So the antibodies are chasing something which is constantly able to alter itself and escape from that. Since the antibody approach alone is not going to work we are taking a different strategy, which is to induce the T cell arm of the immune response. We are using viral vectors, adenoviral vectors that contain large parts of the Hepatitis C virus genome itself to induce an immune response, a T cell immune response, against Hepatitis C.
Q: How would a prophylactic and therapeutic vaccine work?
EB: A prophylactic vaccine works by preventing infection in the first place and the idea here is that when you give someone a vaccine you induce the immune response so that it has a head start. Then when the person is exposed to the virus the immune system is already set in play. Whereas with a therapeutic vaccine you are trying to get rid of an infection that is already well established and that is much more difficult to do.
Q: How far away are we from a vaccine against Hepatitis C?
EB: We are still some years away, but progress is very fast at the moment. Here in Oxford at the moment we have one Phase-I study that has just finished and two that are currently in progress. We are using T cell vaccines that are the most potent described to date. Phase-II studies of one of those are just beginning in the United States. I think for a prophylactic vaccine there is real hope that is going to come in the next few years, a therapeutic vaccine will take longer. Most of the work to develop a T cell vaccine has been done against a particular genotype. There are six different genotypes which reflect differences in the structure of the virus. Within the UK many patients are not infected with genotype 1 strain, but genotype 3 and one of the other things that we are working on within our laboratory is trying to understand the immune system against genotype 3 infection. That will be particularly relevant to the UK population.
Q: What is the most important lines of research that have developed over the last five or ten years?
EB: Something we have been working on in our lab now for the past ten to fifteen years has been understanding the fundamental biology around the immune system and how that targets the virus. What is fascinating about this infection is that a significant minority of patients can get rid of the virus using their own immune response. We have been trying to work out what is it about the immune response in patients that can do that, to patients whose immune response can't, and explore those differences to try to use them in a strategy for developing a vaccine. That is one aspect. We have got some fantastic new drugs that are coming online in the next couple of years which have been bought into patient populations and that will increase the clearance rate in patient populations.
Q: How does your research fit into translational medicine within the department?
EB: We have moved our work foreword from a basic laboratory looking at basic T cell immunology to a situation where we are now giving new products to patients and that is very translational we are very excited about that.