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For the last ten years, the MVA85A Tuberculosis vaccine has been in development in the Jenner Institute and is now tested for efficacy in humans. It is undergoing a phase IIb clinical trial in South Africa and has the potential to provide a life changing vaccination against a disease which kills two million people annually.

Q: The Jenner Institute has recently developed a vaccine to enhance the efficacy of the BCG vaccine. Can you update us on your trial in South Africa?

HF: This is a really exciting time for us because at the end of 2012 we will know for the first time whether our MVA85A vaccine will actually protect infants from TB or not. The design of the trial is what we call a double-blind placebo-controlled trial. Half of the infants received our MVA85A vaccine and half of the infants received a placebo and neither the mother, nor the nurse who gave the vaccine, or the doctor who will be diagnosing any children who develop TB know whether the infants have the placebo or the MVA85A. What this means is that all of us until the trial is un-blinded in December this year, have no idea whether we are seeing any protection or not. It's the safest way to do a trial. It means that we can't influence what the results are but also nerve-racking for us after 10 years of developing this vaccine, it really is both exciting and nerve-racking.

Q: We know about the links between TB and HIV, are there links between TB and malaria?

HF: There aren't links between TB and malaria in the very direct way you that you see links between TB and HIV. TB is a disease that very much affects HIV patients and is the biggest killer in that population. TB tends to affect adults, young adults, whereas malaria affects children under the age of five. But where there is a link is in the type of immune response that's needed for protection from disease. Both of these pathogens hide within human cells so you need a cellular immune response to be able to gain access to where the pathogen is hiding and clear it from our bodies. In that way there is very much a link and when we are thinking about designing vaccines it means that the vaccines we are designing are actually quite similar for the two diseases. In our institute for example, in the Jenner Institute, we work side by side developing vaccines for the two diseases so we can share the same technology and learn from each other's approaches.

Q: What are the most important lines of research that have developed over the past 5 or 10 years?

HF: Ten years ago there were thousands of TB vaccines that had been developed in the laboratory but no vaccines were in clinical trials. Over the last 5 to 10 years we've seen a handful of TB vaccines actually go from the bench and into humans for the first time and that's been a huge step forward for the field and it's something that is very much a focus of our research here in Oxford.

Q: Why does your line of research matter, why should we put money into it?

HF: Having a handful of TB vaccines into clinical trials out of the thousands of potential candidates just isn't enough. This is a very complex disease. Two million people die each year of tuberculosis, a third of the world's population is infected. We know that a vaccine is the most effective tool for tackling infectious diseases world-wide. We need to get more of those vaccines from the bench through into the clinic. We also need to use the best science to really focus in and understand from these clinical trials what makes a good vaccine, what is not so good, so we can keep improving and move forward.

Q: How does your research fit into translational medicine within the department?

HF: In the Jenner Institute, we design vaccines in the laboratory. We do early testing in Vitro and then we actually take them forward into human trials and for me, that is translational medicine. You’re in the laboratory and going right through and seeing something in humans for the first time and then for example, with our MVA85A trial, all the way to see whether you actually get efficacy or not. So, this is the best example, I think of translational medicine - if you take a drug you can see very early on in patients whether you are having an effect or not and then a company can choose to develop that drug or not. Whereas with a vaccine, you are committed, you are going the whole way and so starting off at the bench, right through to the clinic and as a researcher being able to see the whole process, is incredibly rewarding.

Helen Fletcher

Tuberculosis Research

Dr Helen Fletcher works on multi-partner projects to discover biomarkers of protection from TB disease, develop clinical trials capacity in Africa, and develop new vaccines for TB. Dr Fletcher has also developed her own research programme on transcriptional profiling of immune responses following both TB and malaria vaccination.

This podcast presents the research done by Dr Fletcherwhilst working in the Nuffield Department of Medicine. Dr Helen Fletcher now works at the London School of Hygiene & Tropical Medicine.

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