Using a technique devised at the Wellcome Trust Sanger Institute, researchers found that the malaria parasite uses a unique receptor to gain entry and infect human red blood cells. They hope their discovery, which they describe in a study published online in Nature this week, opens a promising new route to the successful development of an anti-malaria vaccine.
Senior co-author Dr Gavin Wright, from the UK’s Wellcome Trust Sanger Institute near Cambridge, told the press they may have found the malaria parasite’s “Achilles’ heel” in how it invades red blood cells:
“Our findings were unexpected and have completely changed the way in which we view the invasion process.”
Malaria is a disease transmitted by bites from mosquitoes carrying Plasmodium parasites. The disease kills around a million people every year, mostly very young children in sub-Saharan Africa.
Once in the human bloodstream, Plasmodium invades red blood cells. This is the stage of the parasite’s life-cycle that leads to symptoms and malaria-related deaths.
At present there is no licensed vaccine against malaria, despite many years of research to find a way to stop the parasite getting into red blood cells. This is not made easy by the fact Plasmodium is highly adaptable; scientists have identified many potential receptors, but none was shown to be unique in that when one was blocked, the parasite switched to another one to gain entry into the cells.
A receptor is a protein that behaves like a gatekeeper. It sits on the surface of cells and only lets in agents that have the correct “key” or ligand, a molecule with a unique shape that binds only with that receptor.
But in this study, the researchers found one particular receptor for which the parasite appears to have no alternative to switch to.
Senior co-author Dr Julian Rayner, also of the Sanger Institute, said:
“By identifying a single receptor that appears to be essential for parasites to invade human red blood cells, we have also identified an obvious and very exciting focus for vaccine development. The hope is that this work will lead towards an effective vaccine based around the parasite protein.”
Wright, Rayner and colleagues used a technique they developed at the Sanger Institute, called AVEXIS, which is short for “Avidity-based Extracellular Interaction Screen”. The technique is designed to detect the type of receptor-ligand encounter that occurs with the malaria parasite.
The researchers found the interaction and showed that disrupting it completely stopped the parasite from being able to get into the red blood cell.
And not only this, they also showed this was true of all the parasite strains they tested, which would suggest this receptor is a universally unique entry pathway.
They write in their paper:
“By systematically screening a library of … proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth …. invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested.”
For a vaccine to be effective, it has to pass a lot of hurdles, not just in the lab, but also in the field, both scientifically and economically. It has to be cost-effective, simple to administer, and capable of creating immunity in the majority of those who receive it.
Professor Adrian Hill, Wellcome Trust Senior Investigator at the Jenner Institute, Oxford, said while recent reports of vaccine trials already taking place in Africa are encouraging, we will still need more effective ones, if we are ever to eradicate malaria completely:
“The discovery of a single receptor that can be targeted to stop the parasite infecting red blood cells offers the hope of a far more effective solution.”
Written by Catharine Paddock PhD