Simon Draper: Progress in Malaria Vaccine Research
The malaria parasite is a highly evolved and complex organism, a ‘master of disguise’. Whilst the development of a vaccine has proved difficult, targeting a pathway essential for the parasite has led to the neutralisation of all strains of Plasmodium falciparum. This is an important step towards developing a vaccine against one of the world’s major killers.
Q: Why is it proving such a challenge to develop a vaccine against malaria?
SD: There are a number of reasons why it has proved so challenging; most of the vaccines that we have already are based on bacteria and viruses, and in the past they have proved relatively successful. Malaria is actually caused by a parasite called Plasmodium, and the parasite is a highly evolved and complex organism. It is also a master of disguise - it changes its appearance at each step of the infectious process in the body so that is one of the reasons why it has proved very challenging. I think one of the others is that the classical way of making a vaccine is to take the whole organism, the whole bacterium or the virus and to inactivate it and to inject that as your vaccine. That can be done for malaria, and we can do that experimentally, but it has been very hard to deploy that into a product - it is actually even hard to grow the parasites in the lab - so that has not been possible and it has actually been challenging for scientists to find other ways of inducing protective responses.
Q: Is there an Achilles heel in the malaria parasite?
SD: Achilles heels are really the holy grails of research; you could define them as a function of the parasite that is absolutely critical to its survival. They are traditionally quite hard to find, but it doesn't mean they are not there if you don't look hard enough. My group actually works on vaccines that try to kill the parasite in the blood, when the parasite is replicating in someone's blood stream and that is when they become sick. Very recently a pathway has been described that appears to be essential for the parasite to get inside a red blood cell, and what we have shown is that antibodies against that pathway can neutralise that process, and it neutralises all strains of malaria parasite. That is a very exciting result, it is very promising and would represent an Achilles heel so to speak.
Q: What is the next step now?
SD: Our group is very much focused on translational research, we aim to take our most promising candidates from the laboratory and into the clinic. What we will look to do now is manufacture that vaccine as clinical grade material, and then we will aim to do a series of proof of concept clinical trials. We will vaccinate healthy adult volunteers here in Oxford, and first of all we will look at the safety of the vaccine. After that we will look at the immune responses induced by that vaccine, and primarily the antibody responses, and if those are looking good and they appear to kill the parasite in our experiments in the laboratory we would then go on to see if the vaccine is actually efficacious and whether it could kill malaria parasites in the blood.
Q: What are the most important lines of research that have developed over the past five to ten years?
SD: There are always a lot of lines of exciting research. I think one of the most exciting has been the expansion in genetics and in genomics: in the last ten years the malaria parasite genome was published and that revealed the parasite has over five thousand different genes. Now all of those encode a different protein, and in the past only a small handful, maybe ten to fifteen have been tested as vaccine candidates, so there is certainly a lot of exciting work to come in the future testing all those new possible proteins that have come from the genome. I think one of the other exciting areas has been the improvement in vaccine technologies: the technologies that we have today are actually capable of inducing immune responses that are much stronger than anything we have seen in the past, and that is both for antibodies and T cell or our white blood cell responses, so that is all looking extremely promising in terms of future vaccine development.
Q: Why does your line of research matter, why should we put money into it?
SD: Why do I think it's important? I think there are a number of reasons! First of all malaria continues to exert a huge burden on global public health, it affects hundreds of millions of people every year and leads to the death of just under a million individuals, primarily children under the age of five years in the developing world, so I think we have a humanitarian obligation to try and do something about that. Also if you look throughout history vaccines have made a huge impact in terms of reducing the burden of infectious diseases and they are highly cost effective, so I think they are certainly very worthwhile developing. I think that maybe a final reason is that we are fairly fortunate in malaria, we know that you can induce immunity to the parasite, we can do that experimentally, and after many years of exposure in the field people become naturally immune, so we know it can be done it has just been a challenge to develop a vaccine in a vial that you can then use to vaccinate people. But just because something is difficult I don't think we should give up, I think it is very important that we keep trying.
Q: How does your research fit into translational medicine within the department?
SD: My group is within the Jenner Institute which is the vaccine department of the University. There we work on a wide range of difficult infectious diseases, and as a group we focus on the development of vaccines that induce antibody responses. A lot of the technologies and vaccine delivery platforms that we have developed are actually now being used against other viral and bacterial diseases, so I think it is important within the department that people can learn from what we have developed just as much as we can learn from what the other groups are doing. I think one of the other important aspects is that we are very much focused on translational research, we want to take our best vaccine candidates from the laboratory and into the clinic, and undertaking clinical trials of the most promising approaches is certainly a very important aspect of doing translational medicine.