James Merson, chief scientific officer at the Vaccines Research Unit at Pfizer, talks about the future of vaccines, from Alzheimer’s drugs to cancer cures.
The Future of Vaccine Development Now this is the next great frontier. We’ve done pretty well over the last century or so to generate prophylactic vaccines, that is vaccines that prevent infectious diseases and smallpox has been pretty much eradicated throughout the world. Polio is almost nonexistent, mumps, rubella. They really are diseases of the past, but what we’ve now learned about how the immune system works, are we in a position to ask the immune system to recognize what we would call a self protein that is one that doesn’t belong to an infectious organism? Our body generates proteins all the time, but our immune system has evolved as we grow up to recognize those proteins as self and doesn’t mount an immune response against them. However, one can envisage being able to trick the immune system to recognize some of these proteins as being foreign. So proteins that we associate with disease we may want to remove from the body via the immune system. Come examples would be as you mentioned Alzheimer’s disease. We know that in Alzheimer’s disease there are proteins which are made or cause the disease, which we would called aberrant proteins. They’ve been somehow changed from the normal type of protein and because they’ve been changed, the immune system can now see that they are different from normal, physically bind to those proteins and remove them from circulation. Indeed, there have been clinical studies targeting Alzheimer’s-causing proteins and indeed there has been clinical benefit derived from the reduction of these aberrant proteins as a result of the vaccine. So whereas it might sound a little bit farfetched because people associate vaccines with pediatric or infective infant disease and preventing infectious diseases, we can envisage how we could harness the immune system to manage certain diseases which are causing real problems in the developed world. Another area that we are looking at, doing what we call therapeutic vaccines, that is to treat the disease as opposed to prevent the disease and that would be in cancer. A cancer has some similarities to infectious disease because cancers arise from the genetic changes that are ongoing in our bodies all the time, which generate what we call tumor antigens that are associated with tumor cells. And cancers are effectively arising from cells where their normal state is no longer maintained and they grow uncontrollably and these uncontrolled cells are associated with known tumor antigens. By targeting these tumor antigens for the immune system, viral vaccine, we can see that the immune system can kill these tumor cells and treat the cancer, so whereas during early days in the realms of cancer we do see encouraging progress being made in the clinic. We’ve had 20 odd years of abject failure in cancer vaccines, but once again, as we understand how tumors are able to evade the immune system and how we can now more specifically up-regulate the immune system, we believe that we can help the immune system also cure us from cancer. So vaccines have been with us for hundreds of years when we look back to smallpox vaccines. They really have been the spine, the main route for public health management. Vaccines prevent infectious diseases and do so very efficiently. However, there are still some infectious diseases which have been resistant to us to be able to generate a vaccine. Some of the ones that you’re all familiar with like HIV, tuberculosis, malaria, each of those organisms have managed to generate mechanisms with which to evade the human immune system. And yet these diseases have tremendous toll on human life and morbidity, so whereas we have been successful for many infectious diseases, at least those three diseases still require very innovative and different ways of thinking about generating a vaccine and for each of those areas encouraging progress is being made both at the research level and also the clinical development level. Whether those clinical development programs are being run by pharmaceutical companies or by non-government organizations encouraging progress is being made certainly against malaria and certainly against TB. Now if we move beyond infectious diseases and preventative vaccines for those and start to think about therapeutic vaccines and vaccines to treat disease then that opens up a whole new vista and what we have learned about the immune system certainly gives you encouragement that we can generate very specific and hopefully expectantly safe ways of being able to harness the immune system to take out aberrant proteins that are associate with disease. And again, there is encouraging progress on this front. Only last year a vaccine to manage hypertension showed very encouraging results in the clinic where a vaccine generated against a protein called angiotensin II was successfully reduced in its concentrations in the circulation system and as a result blood pressure reduction was achieved. So very encouraging progress that we can target human proteins, self proteins, reduce their concentration and generate the desired clinical benefit. So I think there is great scope for therapeutic vaccines as an alternative modality for managing disease in the future. That’s a really difficult question because there are so many diseases which have such high mortality, such high morbidity. HIV is still a tragic disease. Malaria has some of the highest mortality rates for any disease in the world. Tuberculosis. But then you look at Alzheimer’s and the morbidity associated with that. Rheumatoid arthritis, all those diseases require cost effective easily accessible means of better disease management and certainly one can envisage vaccines playing an important role in managing those diseases in a different way than we can currently. So if I were to pick one I probably would have to go with malaria, simply because the death toll from that on a weekly basis far outweighs any of the other diseases.