Transmission blocking malaria vaccines
This year’s World Health Organisation (WHO) World Malaria Day (on 25th April) has the theme of ‘Defeat Malaria’. Nearly half the world’s population is at risk of contracting the disease, and millions are affected by malaria every year. As part of the effort to defeat malaria, researchers at the NDM have been developing vaccines to fight the disease.
Q. How do ‘transmission blocking’ vaccines try to prevent malaria?
Sumi Biswas: Transmission-blocking malaria vaccines aim to block the sexual development of the malaria parasite (Plasmodium falciparum) while it is inside the mosquitoes that transfer the parasite from infected to healthy humans.
When a mosquito bites a malaria-infected person it picks up the male and female malaria parasites in its blood meal. The parasites then completes several developmental stages (including fertilisation) within the mosquito, to get to the form that can cause an infection in humans.
The malaria parasite cannot complete its life-cycle without female Anopheles mosquitoes, so we are aiming to develop vaccines that induce immunity against the mosquito-infecting stages of the parasites. The goal is to induce antibodies in humans, which are then taken up by mosquitoes together with the parasites during a blood meal. These antibodies then interfere with the development of the malaria parasite inside the mosquito, blocking the transmission of the disease to a healthy person.
Q. How are you trying to achieve this goal?
SB: We are developing candidate vaccines that can induce antibodies against antigens expressed on the surface of the parasite and/or mosquito that are crucial for development of the parasite. .
We are testing a variety of vaccine platforms, like virus-like particles, nanoparticles and viral-vectors to induce the high levels of antibodies likely to be required against these antigens. We initially test these in pre-clinical models: we feed mosquitoes a mixture of blood containing parasites and the vaccine-induced antibodies, with the hope that the antibodies will ‘clear’ the parasite within the mosquito during the time that it usually completely its life-cycle within the mosquito.
We have already completed some of these pre-clinical trials, so the next step is clinical development and testing for promising candidates, by vaccinating humans. We will be conducting a Phase I human clinical trial in Oxford this year.
Q. How is this approach different to targeting other stages of the Plasmodium life cycle to prevent malaria?
SB: Traditionally vaccines target the liver and the blood stages of the parasite’s life cycle in humans, but transmission blocking vaccines aim to induce immunity against the stages of the parasites which infect mosquitoes. One way of targeting malaria has always been to prevent transmission of the parasite by using insecticide-treated bed nets, which prevent the mosquito from biting someone. With an effective transmission blocking vaccine, you could achieve the same thing by preventing malaria transmission, which is going to be important if we aim for malaria elimination/eradication. Recent work has already shown the biological feasibility of such vaccines, and models have shown their potential contribution to reducing overall transmission in malaria-endemic communities.
Q. What challenges do we still need to tackle to have an effective malaria vaccine?
SB: Malaria has spent a long time evolving ways to avoid our immune system: many antigens which are protective in pre-clinical models are not so effective in humans. So one of the major challenges has been to develop vaccine delivery platforms that can induce the required immune response to achieve protection in humans. After decades of research on malaria vaccines, we realise that one vaccine on its own is probably not going to be enough to combat this disease. We need to develop vaccines targeting multiple-stages of the parasites life cycle. For this we need to carefully select and combine protective antigens from the different stages: there are a lot (more than 5000 genes) to choose from!