Sumi Biswas: Can we block malaria transmission
Since an effective vaccine is not yet available for malaria, Dr Biswas works on a vaccine that could block malaria transmission. Vaccinated individuals would produce antibodies that prevent the parasite from developing within the mosquito host, which is then unable to transmit the parasite to another individual.
Q: What are transmission-blocking malaria vaccines?
SB: The malaria parasite Plasmodium requires two hosts to complete its life cycle: a human host, and the female anopheles mosquito. The female anopheles mosquito transmits the parasite from one infected individual to another. When one is infected, initially the parasite reaches the liver and causes what we call the 'liver stage infection'. After about 7 to 10 days in the liver the parasite enters the blood stream and multiplies within the red blood cells – during this phase the symptoms of malaria are evident in humans. During the blood stage infection the male and female forms of the parasite are also developing in the blood and these circulate in the blood stream. When a mosquito bites an individual who is infected with malaria, it picks up the male and the female forms of the parasite in its blood meal. The male and the female parasite will then go into the mosquito's midgut, and as soon as they reach the midgut they will activate and fertilise to form the next stage of the parasite. The parasite will then go through several sexual development stages within the mosquito, to get to the stage where it can cause an infection in humans. Traditionally vaccines target the liver stage and the blood stage of the parasite, which are the stages that affect humans, but transmission blocking vaccines aim to prevent the development of the parasite within the mosquito. The aim is to vaccinate humans, so that the antibodies generated in humans can be taken up together with the parasites and they will prevent the parasite from developing within the mosquito – then the mosquito can't transmit the parasite to another individual.
Q: What stage is the research at currently?
SB: At the Jenner Institute we have generated several candidate vaccines, which in pre-clinical studies have shown that we can induce antibodies, which can then be taken up by the mosquito in a blood meal. We have shown that these antibodies can block the development of the parasite in the mosquito, so the mosquito is unable to transmit the parasite to another individual. We do this by actually rearing anopheles mosquitoes, which is the mosquito species responsible for transmitting malaria. We have an insectary where we grow these mosquitoes and then we feed the mosquitoes a mixture of the malaria parasite, as well as the antibodies that we have generated, by vaccination. The hope is that after leaving the mosquito for the time required for the parasite to develop, there will eventually be no parasite in the mosquito. We know from proof of concept studies in pre-clinical models that this can be achieved in the lab.
Q: What is the next step now?
SB: Once we've established proof of concept the next step will be to vaccinate humans, so in Oxford we would look into doing Phase I human clinical trials. We would manufacture the vaccines as clinical grade material then use them to vaccinate humans. Once we are ready, we will recruit volunteers in Oxford and vaccinate them. The primary aim of these Phase I trials is to look at the safety of the vaccines first of all; from previous experience with similar kinds of vaccines, we know these vaccines are safe, however, with every new vaccine we must do a Phase I study to assess its safety. Once we assess the safety, we will collect blood samples from these volunteers and we will look to see if we have been able to generate antibodies in humans. We will then use the same feeding assay to test if the blood serum from the volunteers is capable of blocking the development of the parasite in the mosquito. So in the Phase I studies, if we can show that we can replicate what we have seen in the lab, in humans, and the results are promising, the next step would be to test the vaccine in a malaria endemic area.
Q: What are the most important lines of research that have developed in the past 5 or 10 years?
SB: Importantly, the malaria parasite genome has been sequenced and we have gained more and more knowledge over time about the biology of the parasite, and the way the parasite interacts with its host, whether it is the mosquito or the human. This information will help us to design better vaccines. I think vaccine strategies and vaccine technologies have also improved over time, so now we have a varied range of technology that can be used to induce better immune responses, which have clearly helped vaccinology a lot. In terms of having lots of candidates to choose from, different labs have worked to develop new assays, which are now being standardised across the field. These assays help us to choose the best candidates to be translated to humans and tested in humans.
Q: Why does your line of research matter, why should we put money into it?
SB: Malaria is a huge public health burden. We know the most advanced malaria vaccine called RTS,S is in Phase III clinical trials and has been recently in the news, with early indications showing that the efficacy of the vaccine is only about 25 to 30%. In the field we realise that this vaccine on its own is not going to be enough, so we need to work on other vaccines, or better vaccines, that we could use alone or maybe in combination with RTS,S. One way of targeting malaria has always been to prevent transmission of the parasite by either using insecticide treated bed nets, which prevent the mosquito from biting someone, or with an effective transmission blocking vaccine, you could achieve the same thing by stopping malaria transmission, which is going to be very important if we are ever going to achieve the goal of elimination, or even eradicating malaria.
Q: How does your research fit into Translational Medicine within the Department?
SB: The Jenner Institute aims to develop vaccines against a variety of infectious diseases, and the field of vaccinology isn't complete without translating the ideas that we develop in the lab into the clinic. This is why the ideas that we develop in the lab are tested in human clinical trials in Oxford and then later in other parts of the world. My research group also work to look at other ways and technologies to improve antibody responses. These technologies can then also be applied to a number of different vaccine applications throughout different diseases.