Francis Ndungu: Immune response against malaria
Malaria vaccines created in Europe or America might work well for naïve individuals but not in endemic areas. Immune responses to malaria differ in naïve or exposed, or historically-exposed populations; in endemic regions some people become immune to malaria. Understanding naturally acquired immunity to malaria aims to inform the development of better malaria vaccines.
My name is Francis Ndungu and I am from the KEMRI Wellcome Trust Programme in Kenya. The Cellular Immunology Group includes scientists who are studying the cells of the human immune system and the products that they make, in order to understand how people become immune to diseases either following natural infection or immunisation. This group has people working with HIV and other viruses, it’s got people working with malaria, and there are also people working with malnutrition. I am personally interested in malaria and malaria vaccines. My work includes understanding naturally acquired immunity, and picking whatever lessons we can learn to develop a malaria vaccine.
Malaria immunology in Kilifi is based on two platforms: one platform is conducting long-term longitudinal studies in children, and the other platform is using experimental medicine where we infect people who have been exposed to malaria, in order to identify individuals who are immune to malaria. If we can identify people who are immune to malaria, and then we compare their immune responses to malaria with people who are not yet immune, then we can identify immune responses that can be used to identify antigens that we can include in vaccines.
Another way that my work would help in developing malaria vaccines is help understand why it is so difficult to immunise people who live in endemic areas. One of things we have learnt over the last few years is that if you develop a vaccine in Oxford or in America, those vaccines actually tend to work quite well in animal models and in malaria-naïve individuals. But when you move them to malaria-endemic areas they are not very immunogenic, and they are not as protective. It appears that prior exposure to malaria modifies the immune system, making it more difficult to immunise people. And my work is also trying to understand what that modification is and how it can be counteracted in delivering an effective vaccine.
One of the most exciting research projects we have conducted in Kilifi recently is comparing the immune response to malaria in individuals who are currently infected with malaria, people who are living with constant infections - these are people who are being persistently infected, or they have chronic infections. We also have another group of individuals who were exposed to malaria a long time ago, but they are no longer exposed to malaria because malaria has been controlled in the area where they live. In other words, it’s like comparing immune responses to malaria in individuals who are currently living with malaria and individuals who were historically infected a long time ago. We have found that current exposure interferes or impairs the ability of the cells in these individuals to respond to malaria antigens in the way we would expect.
In the last five to ten years, one of the great things that had happened is that funders like the Wellcome Trust have decided to support experimental human medicine. For infections like malaria, where it’s easy to treat the disease, you can infect people who are semi-immune to malaria in order to understand immunity to malaria. That is one of the things we do in Kenya at the moment. That is very exciting because the immuno-epidemiological studies that are happening in the field are confounded by many factors; that makes it had to make conclusive decisions on which antigens we can use for vaccines. Other things in the range of investigations that have come up in the last five to ten years is that we have seen improvement in high-throughput technology for screening antigens that can be included in vaccine. And in the world of immunology, people have learnt how to make human monoclonal antibodies. These human monoclonal antibodies, especially in the case of HIV and also immunity in cancer, are actually being considered as therapeutics, immuno-therapeutics. In some cases, in infectious diseases we can use these monoclonal antibodies in the discovery for antigens that could be used in vaccines today. And in some cases the same monoclonal antibodies can be used to block the undesirable immune responses that may result in the immune response causing disease or interfering with immunisation.
I think it is really important for us to understand naturally acquired immunity to malaria. Because malaria continues to be a major public health issue in the countries in Africa and in Southeast Asia. What we have seen in the last three years, even though we have effective drugs for treating malaria and insecticides for controlling malaria through killing mosquitos, is that the malaria control has stalled. We need new tools to be included, together with the current tools to drive malaria transmissions down further. My research will inform the design and the development of new vaccines and other therapeutics.
This interview was recorded in September 2019