Professor Arturo Reyes-Sandoval aims to develop a novel malaria vaccine against Plasmodium vivax, one of the four malaria parasites that affect humans. P. vivax is found in Africa, Asia, Latin America and the Western Pacific: 40% of the world’s population is exposed to the disease that is responsible for around 130-350 million clinical cases every year.
P. vivax is difficult to eradicate since the parasite can evolve into a hypnozoite, a small structure that can hide dormant in the liver of an infected person for a long time. Dr Reyes-Sandoval uses recombinant viral vectors which stimulate antibodies as well as T cell responses, to prevent and treat 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: Can you tell us about the different types of malaria parasites?
A.R: Malaria is caused by the Plasmodium parasite. There are around 200 species of this parasite and they can infect a wide variety of animals including birds, reptiles, rodents and primates. Of these 200, only 4 are generally considered able to infect humans and cause malaria. These are known as Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale and Plasmodium malariae. Plasmodium vivax is the most widely distributed form of malaria in the world and it can be present not only in Africa but also in the Western Pacific, and importantly in highly populated areas of Latin America and Asia, where it is a big problem. Plasmodium falciparum is mainly present in Africa and is responsible for high levels of mortality, mainly in children. Malariae and ovale are two species which are less prevalent around the world.
Q: What challenges does Plasmodium vivax pose?
A.R: The main challenge of this form of malaria is called hypnozoite. This is a very small structure that the parasite evolves into and it uses it to hide inside the liver of an infected person. The parasite can remain dormant for days, weeks, months or even years. The fact that the parasite can hide inside a person without being recognized makes it extremely difficult to eliminate from the places where it is present. To give you an example, there have been places, countries where malaria has been attempted to be eliminated. These are places where both falciparum and vivax co-exist. After different attempts for elimination only Plasmodium falciparum could be eliminated but vivax remained, and this is because it forms this kind of structure but falciparum does not.
Q: How far away are we from a vaccine?
A.R: This is very difficult to predict. Vivax vaccine development is in the early stages of development in comparison to Plasmodium falciparum which is more advanced. For falciparum for instance, in the 1980s it was considered that by 1990 there would be a vaccine already and it has been more than thirty years and so far there is no vaccine available for falciparum malaria or for any other parasitic disease. So it’s quite difficult to know. In my case I’m planning to develop a vaccine and test it in humans within five years. If everything goes well and we succeed, we will be able to test it in field trials within ten years.
Q: Can your research help develop other vaccines?
A.R: Absolutely. The kind of tools that we have available work in a different way compared to traditional vaccines. Traditional vaccines can stimulate mainly or only one arm of the adaptive immune responses which are called antibodies, whereas viral-vectors can induce not only antibodies but also T cell responses or cytotoxic lymphocytes. This type of cells can eliminate other infected cells when a parasite or a virus goes inside a cell. For certain diseases this kind of T cell inducing vaccine could be very important in their ability to prevent it. For instance Chagas disease, which is a neglected tropical disease caused by another parasite, Trypanosoma cruzi, can be highly benefited by T cell inducing vaccine. Another example I am thinking of is dengue.
Q: What are the most important lines of research that have developed over the past 5 or 10 years?
A.R: In my opinion it is our ability to produce genetically modified micro-organisms. One example, for instance, is the recombinant viral vectors that we use as vaccines. At the Jenner Institute, the vector core facility has been able to produce nearly 400 recombinant viruses in the last three to four years, and all of them can be used as vaccines. Another field of great interest to me is our ability to create recombinant parasites. One of my favourites is a malaria parasite that can express transgene or a protein from the fire-fly; it can produce light and we can follow up the infection in real-time.
Q: Why does your line of research matter? Why should we put money into it?
A.R: Because vivax malaria is a human tragedy. We are talking about a disease that is responsible for around 130-350 million clinical cases every year, and nearly 40% of the human population is exposed to this disease. It mainly affects children or young people of working age, so this disease leads to poverty. We are now very fortunate to have tools that can induce extraordinary immune responses that we have never been able to achieve, and I think it will be desirable to use these tools to eliminate this disease.
Q: How does your research fit into translational medicine within the department?
A.R: The Nuffield Department of Medicine has a great tradition in vaccinology. It hosts groups that are making major progress in the development of vaccines against HIV, malaria, tuberculosis, and influenza to name just a few. I believe that vaccine development is one of the best examples of translational medicine because we, as vaccinologists, are aiming at developing one product that can be used in animals or humans to prevent a disease.