A rare variant of blood, found only in parts of East Africa, can help the body resist malaria even better than our best vaccines.
Now, scientists think they understand how this is possible and it is not a defense we have considered before.
Malaria is caused by five species of mosquito-borne plasmodic parasites, which cause the deaths of half a million people worldwide, many of whom are children.
The disease works by infiltrating our red blood cells, using a “lock and key” system. While much vaccine research has focused on changing the lock of our blood cells or hijacking the key, the Dantu gene variant eliminates the door itself.
“The Dantu variant actually increases the tension on the surface of the red blood cells slightly,”
“It’s as if the parasite still has the key to the lock, but the door is too heavy to open.”
The malaria vaccines we currently have are far from perfect, conferring only 35% protection against the deadliest forms of the disease. Drug developers know we can do better because there are humans who do it naturally.
In 2017, after sifting through thousands of genomes in Kenya, scientists discovered the Dantu blood variant, a genetic oddity related to human blood cells that appeared to provide incredible natural resistance to malaria.
In the coastal town of Kilifi, a single copy of the Dantu gene conferred up to 40% protection against all forms of severe malaria. And when individuals inherited two copies, one from each parent, resistance reached 74%.
It is almost on a par with the sickle cell trait, famous for its protection against malaria and the serious disease that can accompany multiple copies.
However, two copies of the Dantu gene do not appear to cause adverse health effects; they simply add more protection against malaria.
By analyzing blood samples from 42 healthy children in Kilifi, researchers have now tested how Dantu red blood cells respond Plasmodium falciparum, the deadliest form of malaria.
A microscopic time-lapse video reveals that Dantu red blood cells prevent this parasite from entering by creating a tighter cell membrane, a previously unknown defense.
We are still not sure what leads to this tighter membrane, but the authors think that by modifying the expression of some membrane proteins, the variant of the Dantu gene pulls the cell tense like a drum, eventually stopping the infection and further proliferation in the blood.
Analyzing blood samples at fine resolution, the team found many more parasites entangled in red blood cells with lower surface tensions.
This may explain why P. falciparum tends to prefer younger red blood cells, which generally have a lower voltage.
Even among children with zero copies of the Dantu gene, the researchers found that membrane tension had an effect on malaria infection.
If we can figure out how exactly the Dantu gene affects membrane tension, we might be able to build a vaccine that turns off the blocking mechanism in a similar way, providing far greater protection against this deadly parasite.
“The red blood cell membrane only needs to be slightly tighter than usual to block the entry of malaria parasites,” says biophysicist Viola Introini of the University of Cambridge.
“Developing a drug that emulates this increased tension could be a simple but effective way to prevent or treat malaria.”
The study was published in Nature.