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Page 1 — “I expect we will have eliminated malaria in 30 years”
Page 2 — “African researchers ask: Where the hell is the vaccine?” Page 3 — “We could imagine that it would become a travel vaccination”
Hardly any current invention is likely to save as many lives as the malaria vaccine that Adrian Hill helped develop. How does the vaccine work and what happens next with the infectious disease that still kills hundreds of thousands of children every year?
TIME ONLINE:
Mr. Hill, do you still remember your first malaria patient?
Adrian Hill:
I worked in Gambia for the first time in 1988. I don’t remember a single patient, there were so many. Most were still babies. Many were unconscious, only waking up now and then. A lot of people died. In the following two years I was there again during the rainy season and each time it was the same disaster.
TIME ONLINE:
What did you do in Gambia?
Adrian Hill
is an Irish vaccine researcher. He has been dedicated to finding a vaccination against malaria for decades. Hill heads the renowned Jenner Institute at the University of Oxford. He was also instrumental in the development of the AstraZeneca vaccine against Covid-19. In 2023 he received the highest British civil award for his research.
Hill:
I wanted to research why some children become seriously ill with malaria and others don’t. At that time, we managed to demonstrate that certain genes that control the immune response influence this risk (Nature: Hill et al., 1991). I was fascinated by malaria immunology. Vaccinations were the next logical step. In 1993 I began working on a first vaccine candidate, and in the 30 years since then I have developed countless others. I not only wanted to understand malaria, but also to ensure that we finally defeat this cruel disease. I can now say: Malaria should not be with us for another 30 years; I assume that we will have wiped it out before then.
Malaria
What is Malaria?
Malaria is a parasitic disease. The pathogens, so-called Plasmodiumare transmitted via mosquito bites and go through different stages in the human bodyespecially in the Leber and in red blood cells. Typical symptoms are flu-like symptoms, Gastrointestinal problems and Fever, that comes and goes. Later it can lead to kidney failure, clots throughout the body and destruction of blood cells, leading to anemia. There was no vaccination until the middle of last year.
According to the World Health Organization (WHO), 608,000 people died of malaria in 2022, most of them Children under five years old. Sub-Saharan Africa is most affectedhalf of all deaths worldwide were recorded in just four countries: Nigeria, the Democratic Republic of Congo, Niger and Tanzania.
TIME ONLINE:
About 20 years ago, around a million children worldwide died of malaria every year. Various measures, such as bed nets, controlling mosquitoes with pesticides and the use of preventive medication, have succeeded in reducing this number by around a third.
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Hill:
But that is not enough. It was clear that malaria could not be controlled without an effective vaccination. And children must receive this vaccination in their first year of life. Most children die of malaria in their first year of life.
TIME ONLINE: A first malaria vaccine called RTS,S from GlaxoSmithKline has recently been rolled out in Africa. However, experts have particularly high hopes for the protein vaccine R21/Matrix-M, which you played a leading role in developing and which the WHO also recommended in the autumn. It should be used this year. Why could he of all people bring about the turning point?
Hill: RTS,S is already much more effective than previous vaccine candidates. But I am convinced that our R21 vaccine is significantly better. We are the only ones to have cracked the goal of 75 percent effectiveness that the WHO set ten years ago.
TIME ONLINE:
So is your vaccine a breakthrough in the fight against malaria?
Hill:
The idea for a malaria vaccine is more than a hundred years old. But it was only in the 1980s that it was possible, using molecular biology, to identify antigens on the malaria parasite against which it was hoped to be able to vaccinate. One of these antigens looked so promising that it was announced at the time that there would be a vaccine in five years. We now know that five years was too optimistic. But the antigen was the right one. It is in both the RTS,S and our R21 vaccine.
TIME ONLINE:
You don’t like the word “breakthrough,” do you?
Hill:
Science doesn’t work in breakthroughs. Insights always build on previous insights and the work of other people. But in terms of effectiveness, R21 and RTS,S are certainly a breakthrough compared to all previous malaria vaccines.
Malaria vaccines
The new malaria vaccines
The first malaria vaccine recommended by the WHO war Mosquirix or RTS,S/AS01 from GlaxoSmithKline. It is already being used in various countries. However, he is In short supplya total of only 18 million doses will be available by 2025.
In autumn 2023, the WHO finally recommended the vaccine that Adrian Hill helped develop, R21/Matrix M. Hill and colleagues demonstrated its effectiveness in a study with around 5,000 babies and toddlers in five countries (Lancet Preprint: Datoo et al., 2023).
Both vaccines contain a protein from the surface of the parasite Plasmodium falciparumwho the causes malaria tropicathe form of malaria, which has the highest number of illnesses and deaths in the world caused.
TIME ONLINE:
Why did it take so long to find an effective vaccine against malaria?
Hill:
The malaria pathogen is at least 30 million years old and has probably been infecting humans for as long as they have existed. He has always found ways to evade our immune system. This is especially true for Plasmodium falciparum, the causative agent of the most dangerous form of malaria. The parasite changes its surface as the infection progresses. So it constantly looks different to the human immune system and it has difficulty grasping it. This makes it significantly more difficult than with Sars-CoV-2, for example, to find the antigen against which you want to vaccinate. With the coronavirus, it was obvious that you had to take the spike protein with which it docks to the cells. There is no such thing with malaria. The parasite’s genome includes 5,000 genes, and experts have argued for decades about what could be the key to the malaria vaccination. I and many other researchers have worked on countless vaccine candidates, but their antigens ultimately proved unsuitable.
TIME ONLINE:
Both RTS,S and R21 use the so-called circumsporozoite protein (CSP) as a target, which is important during the early phase of the infection, i.e. after the parasite enters the blood through a mosquito bite and before it infects the liver.
Hill: CSP has been the hottest candidate over the decades. But to protect against malaria, a vaccination must produce extremely high levels of antibodies against CSP. Much higher than anything known from corona vaccinations.
TIME ONLINE: Because the antibodies have to catch the parasites before they infect the liver?
Hill: Exactly. You only have minutes for them to reach your liver! After the mosquito bite, the parasites usually travel from the skin through the blood to the liver within ten minutes. Only 20 or 30 parasites are transmitted per bite. But the problem is: if even a single one of them makes it to the liver, it can be fatal. Because when one parasite attacks the liver cell, 20,000 new ones emerge seven days later. This is at a stage of development against which the vaccination is ineffective.
Hardly any current invention is likely to save as many lives as the malaria vaccine that Adrian Hill helped develop. How does the vaccine work and what happens next with the infectious disease that still kills hundreds of thousands of children every year?
TIME ONLINE:
Mr. Hill, do you still remember your first malaria patient?
Adrian Hill:
I worked in Gambia for the first time in 1988. I don’t remember a single patient, there were so many. Most were still babies. Many were unconscious, only waking up now and then. A lot of people died. In the following two years I was there again during the rainy season and each time it was the same disaster.