Prof. Sir Andrew McMichael is working on human immunology and vaccines, first looking at flu virus and now HIV. His current lines of research include analysing early molecular events in HIV infection, T cell immune response to HIV and the use of vaccination to control HIV infection.
Although we know a lot more about HIV, the infection keeps spreading and there is a real need for a vaccine. Various strategies are investigated: either prevent the infection by stimulating really good antibodies, or control it by harnessing the cellular immune response that could prevent the disease.
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: Do we understand HIV any better than 5 or 10 years ago?
AM: We certainly do. We know a lot more about the virus, about how it avoids immune responses and how it establishes itself in the body. We know a lot about the envelope, which is the target for antibodies and vaccines, and we know much more about how to treat it effectively.
Q: What are the major lines of research today?
AM: There is a huge effort going into vaccine development. Despite the treatment there are still 2 million people being infected every year and more people being infected than actually start treatment currently. Although the treatment is being rolled out to Africa and Asia, it is not reaching enough people and it probably never will, so there is a real need for a vaccine.
For most vaccines there is some evidence that, with most viruses, people who are affected are protected from re-infections. If you have had measles you won't get it again, or if you have had chicken pox you won't get it again. With HIV we don't really have that evidence, we don't have examples of people who have cleared HIV and are then totally resistant for evermore. However we do know that a lot of people control the virus infection much better than other people. Some people have survived twenty or thirty years without needing any treatment and they are controlling the virus really pretty well, although they haven't cleared it completely. Others might progress to infection in about a year or even less, and then progress very rapidly. The keys to that really are coming in the very first stages of infection. So the very first immune response people make can determine the whole outcome - whether they will progress rapidly because that response was totally inadequate, or whether it was so good that they actually control the virus very well. One of our aims for the vaccine is to try and mimic the latter. It is not as good as completely preventing infection which is what an antibody might do, but because that is so difficult, and some might say it is almost impossible to get an antibody to neutralise all the variety of HIV viruses that there are out there, this is an alternative way to go to try and make sure the immune responses people make are better and they are less likely to develop disease.
Q: How far are we from a vaccine that prevents HIV infection?
AM: We are a little way closer than we used to be, but we are still a long way off I think. There was a recent trial two years ago in Thailand which took about 5 years to do. It showed that there was a 30% reduction in infection in people who are vaccinated. For a flu vaccine for example we would hope for 100% protection, so 30% is not terribly good but is a lot better than nothing. And if that result can be repeated, and that is a big if, but if it is repeated then I think we have opened the door slightly. I think that it will be possible to improve on that 30% and get it up to 50%, 60%, 70% and then we really would have a vaccine. But that whole process would probably take at least 5 years to get to that more efficient vaccine, and then another 5 years to roll out to give to large numbers, we are talking millions of people.
Q: Why does your line of research matter, why should we put money into it?
AM: My line of research is to try and develop the vaccine. I am not the only person doing that, I am part of many groups around the world who are trying to design vaccines, and there are two kinds of approaches; one is to find something that will stimulate really good antibodies that will neutralise the virus. The other is to either back that up or cover an alternative strategy which is to harness the cellular immune response, or the T cell immune response, which controls virus infected cells and controls infections in the body. It might not prevent infection but it could prevent disease. That is really where our work is going and of course it is important because the infection is so important.
Q: How does your research fit into translational medicine within the department?
AM: Our research, or my research, has been looking at immune responses in humans for longer than I care to remember, I think around 30 years! We started working on flu and looking at ways in which we could use that immune response possibly to develop flu vaccines - Adrian Hill and Sarah Gilbert are now in the department doing that. But my main attention switched to HIV when it became a real problem in the mid 1980s. We have looked at the nature of immune response to HIV, how it works, what controls the virus, and that has led us to developing our vaccine strategy. We now have a new type of vaccine approach that Tomas Hanke and I in the department are trying to develop, also working with Lucy Dorrell, to test that in the very early trials in volunteers in Oxford, and if that looks promising and gets the immune response we want then we will join up with other teams around the world to roll that out into bigger and bigger trials. If everything goes really smoothly we could try it in order to see whether it really prevents infection or controls infection probably in about 10 years time.