The World Health Organization just approved a new vaccine which, according to specialists, will be a game-changer in the fight against malaria, a disease which kills half a million people in Africa each year.
The tests showed that the R21/Matrix vaccine, developed by the University of Oxford in collaboration with the Serum Institute of India, reduces the number of symptomatic cases by up to 75%. It can be manufactured inexpensively and on a large scale. The Conversation spoke to Adrian Hill, chief investigator of the trials, who is also director of the Jenner Institute at the University of Oxford, about his very promising vaccine. Below you will find extracts from the podcast.
Why is the R21/Matrix vaccine a game changer?
We see an effectiveness of around 75% in reducing the number of malaria episodes over one year. The best vaccine used so far had an effectiveness of around 50% over one year, with effectiveness becoming lower over three years.
This is a concrete improvement, but it is not the main progress. The big difference is how to manufacture the vaccine at the scale that is truly needed to protect most of the children who need a malaria vaccine in Africa.
There are approximately 40 million children born each year in malarious areas of Africa who could benefit from a vaccine. Ours is a vaccine that is injected in four doses over a 14-month period, which means that approximately 160 million doses are needed. We can achieve this.
The Serum Institute of India, our partner for the manufacturing and marketing of this vaccine, can produce hundreds of millions of doses each year, while the previous vaccine could only be manufactured at a rate of six million doses per year. between 2023 and 2026, according to information from Unicef.
The third real advantage of this vaccine lies in its cost. We knew full well that we couldn't produce a vaccine for $100 (the equivalent of 94 euros, editor’s note). This would not have been acceptable to international agencies financing the purchase and distribution of the vaccine in very low-income countries.
So we arrived at a price that will vary depending on the scale at which it is manufactured, but should be around $5 (a little less than 5 euros, editor’s note) the dose for production at a large volume.
Why has developing a malaria vaccine been so difficult?
We have been trying to develop vaccines against malaria for over 100 years. More than a hundred vaccines have been the subject of clinical trials in humans. Very, very few of them gave good results.
Malaria is neither a virus nor a bacteria. It is a protozoan parasite, several thousand times larger than a classic virus. The number of genes it has is a good indicator. Covid has 13 genes, malaria has around 5. This is one of the reasons why malaria is extremely complex.
The malaria parasite takes many forms. The initial forms are injected by the mosquito into the skin and quickly travel to the liver. They multiply in the liver for a week before entering the bloodstream. During these different stages, the forms of the parasite are extremely different. They grow actively, multiplying ten times per 48 hours.
When the parasite density becomes very high, you are very ill. If you're unlucky, you'll die, usually from brain symptoms, coma, or severe anemia because the parasites break down red blood cells.
Another stage follows during which the parasite transforms again. It takes the form that will allow the mosquito to absorb it during its next bite. By then going to infect someone else, the mosquito will continue the life cycle of the parasite.
We see how complex the life cycle of infectious pathogens is.
Malaria generally goes through four life cycles, all of which are different. If we manage to develop a very good vaccine that targets one of them, we break the cycle of transmission. That's what we're trying to do.
We strive to target the forms of the parasite called “sporozoites”, which correspond to the forms of the parasite that the mosquito inoculates in the skin. We are trying to trap these sporozoite forms before they reach the liver and continue their life cycle.
Fortunately, there are no symptoms of malaria at this stage. Malaria is a silent infection until the parasite enters the bloodstream and begins to multiply inside red blood cells.
The sporozoite form is therefore a natural target to try to kill the parasite before it begins to actively multiply.
Tell us about past attempts to develop a malaria vaccine
Very early in the history of vaccination, attempts were made to use the whole microbe, in the same way that vaccination pioneer Edward Jenner used the whole virus to vaccinate against smallpox. Then the French microbiologist Louis Pasteur arrived with bacterial vaccines, and so on. Around 1943, a candidate vaccine against the entire malaria parasite was tested in New York but was ineffective. This discouraged scientists for a while.
It wasn't until the 1980s, when we were able to begin sequencing the parasite's genes, that new vaccine candidates emerged. Within ten years, we had 5 vaccine candidates, because all the teams hoped that the gene they had sequenced could be a malaria vaccine. And of course, almost all of these vaccines have failed.
Why are whole parasite vaccines not effective against malaria?
The explanation is the same as that which helps to understand why having been infected with malaria for the first time does not protect you against the next infection.
In malaria areas where we test our vaccines in Africa, some children have up to eight episodes of malaria in three or four months. They are very ill during the first episode, then three weeks later, they have a second episode of malaria, and so on. Natural immunity does not work until you have experienced a lot of different infections. This is why adults are generally protected against malaria and are less sick.
Those who die from malaria in endemic regions are the young children who may never have been infected before. They die during their first infection at the age of one year, or when they have perhaps already experienced one or two episodes of malaria. But this was not enough to give them sterilizing immunity.
Malaria has existed for tens of millions of years. Not only in humans, but also in the species that we were before becoming humans.
It is a very cunning parasite that has developed all kinds of immune escape mechanisms.
When you try to vaccinate, you suddenly understand that it is only when the vaccinated person's body reaches extraordinarily high levels of antibodies – levels of antibodies that the parasite has never encountered before and against which the evolution has not prepared him – for the vaccine to become effective.
Will we one day be able to completely eradicate malaria?
Malaria is very high on the list of diseases we want to eradicate. I don't think this will happen in five or ten years, but rather in around fifteen years. 2040 would therefore be a reasonable objective.
No one is suggesting we stop what we are currently doing in the fight against malaria, using mosquito nets, sprays and medicines. But today we have a new tool that could be individually more protective than any of the tools we currently use.