A rare variety of blood found only in parts of East Africa can help the body resist malaria even better than our best vaccines.
Now scientists believe they figured out how to do this – and it’s not a defense we thought about before.
Malaria is caused by five types of mosquito-borne Plasmodium parasites that claim the lives of half a million people worldwide, many of whom are children.
The disease infiltrates our red blood cells using a “lock-and-key” system. While a lot of vaccine research has focused on changing the lock on our blood cells or hijacking the key, the Dantu gene variant does away with the door itself.
“The Dantu variant actually increases the tension on the surface of the red blood cells slightly,”
“It’s like 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, offering only 35 percent protection against the deadliest forms of the disease. Drug developers know we can do better – because there are people who do it naturally.
In 2017, after combing thousands of genomes in Kenya, scientists discovered the Dantu blood variant, a genetic trait associated with human blood cells that appeared to offer incredible natural resistance to malaria.
In the coastal town of Kilifi, a single copy of the Dantu gene offered up to 40 percent protection against all forms of severe malaria. And when individuals inherited two copies, one from each parent, that resistance reached 74 percent.
This is almost in line with the sickle cell trait known for its protection against malaria and the serious illness that can accompany multiple copies.
However, two copies of the Dantu gene appear to have no adverse health effects. They simply offer more protection against malaria.
When analyzing blood samples from 42 healthy children in Kilifi, researchers have now tested how Dantu’s red blood cells react Plasmodium falciparum, the deadliest form of malaria.
A microscopic time-lapse video shows that Dantu red blood cells prevent this parasite from entering by creating a tighter cell membrane – a previously unknown defense.
We’re still not sure what leads to this tighter membrane, but the authors believe that by altering the expression of certain membrane proteins, the Dantu gene variant pulls the cell taut like a drum and ultimately increases the infection and further proliferation in the blood stops.
When imaging blood samples at fine resolution, the team found significantly more parasites entangled in red blood cells with lower surface tension.
This could explain why P. falciparum favors younger red blood cells that are generally lower in tension.
Even in children with zero Dantu gene copies, the researchers found that the tightness of the membrane had an impact on malaria infection.
If we can figure out how exactly the Dantu gene affects membrane tension, we may be able to engineer a vaccine that similarly switches off the lock-and-key mechanism and offers far more protection against this deadly parasite.
“The red blood cell membrane just has to be a little tighter than usual to prevent malaria parasites from entering,” says Cambridge University biophysicist Viola Introini.
“Developing a drug that mimics this heightened tension could be a simple but effective way to prevent or treat malaria.”
The study was published in Nature.