A rare blood variant, found only in parts of East Africa, can help the body resist malaria even better than our best vaccines.
Now, scientists think they’ve figured out how this is possible – and it’s not a defence we’ve considered before.
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 on our blood cells or hijacking the key, the Dantu gene variant does away with the door itself.
“The Dantu variant actually slightly increases the tension of the red blood cell surface,” explains geneticist Silvia Kariuki of the KEMRI-Wellcome Trust Research Programme in Kenya.
“It’s like the parasite still has the key to the lock, but the door is too heavy for it to open.”
The malaria vaccines we currently have are far from perfect, conferring only 35 percent protection against the deadliest forms of the illness. Drug developers know we can do better – because there are humans who do so naturally.
In 2017, after combing through thousands of genomes in Kenya, scientists discovered the Dantu blood variant, a genetic quirk related to human blood cells which seemed to provide incredible natural resistance to malaria.
In the coastal town of Kilifi, a single copy of the Dantu gene conferred 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.
That’s nearly on par with the sickle-cell trait, which is famous for its protection against malaria and the serious illness that can accompany multiple copies.
Two copies of the Dantu gene, however, don’t seem to cause any adverse health effects; they simply add more protection against malaria.
Analysing blood samples from 42 healthy children in Kilifi, researchers have now tested how Dantu red blood cells respond to Plasmodium falciparum, the deadliest form of malaria.
A microscopic time-lapse video reveals Dantu red blood cells stop this parasite from entering by creating a tighter cell membrane – a previously unknown defence.
We’re still not sure what leads to this tighter membrane, but the authors think that by changing the expression of certain membrane proteins, the Dantu gene variant pulls the cell taut like a drum, ultimately stopping infection and further proliferation in the blood.
Imaging blood samples at fine resolution, the team found considerably more parasites entangled in red blood cells with lower surface tensions.
This might explain why P. falciparum tends to prefer younger red blood cells, which have lower tension in general.
Even among children with zero Dantu gene copies, researchers found membrane tautness had an effect on malaria infection.
If we can figure out how exactly the Dantu gene impacts membrane tension, we might be able to construct a vaccine that shuts down the lock-and-key mechanism in a similar way, providing far more protection against this deadly parasite.
“The red cell membrane only needs to be slightly more tense than usual to block malaria parasites from entering,” says biophysicist Viola Introini from 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.