WEHI researchers have identified how natural human antibodies can prevent malaria parasites from entering red blood cells, potentially indicating how new protective therapies could be developed against this globally significant disease.
Research is helping to better understand how antibodies block the entry of Plasmodium vivax malaria parasites into young red blood cells called reticulocytes. It builds on an earlier finding that the P. vivax locks onto the transferrin 1 receptor (TfR1) to enter cells.
The research, led by Associate Professor Wai-Hong Tham and PhD student Li-Jin Chan of WEHI, alongside Professor Christopher King of Case Western University, USA, has been published in Nature Communications.
In one look
- By examining antibodies from people with a history of malaria infection, the researchers observed that natural antibodies can prevent Plasmodium vivax from attaching to transferrin receptor 1 on reticulocytes.
- One of the ways the antibodies work is to prevent the parasite’s proteins from getting close enough to the cell for the parasite to enter.
- This discovery opens new avenues for the development of antibody-based therapies against malaria.
- Shedding light on pathogen blocking antibodies
Plasmodium vivax is the most common malaria parasite in the world and the predominant cause of malaria in the vast majority of countries outside Africa. It is also the main parasite responsible for recurrent malaria infections.
The malaria parasite is a complex, single-celled organism with various proteins that help it invade red blood cells, reproduce, and spread. Adhesives on the parasite’s surface are key-like proteins that “unlock” cells, allowing the parasite to enter.
Previous studies in Papua New Guinea, Thailand and Brazil have shown antibodies against P. vivax adhesins were correlated with protection against infection and disease, Associate Professor Tham said.
“We wanted to understand how these human antibodies in natural infection prevent the parasite from entering. By extracting and testing antibodies from people who have had P. vivax infections, we have identified the different ways in which human antibodies P. vivax job. One way is to prevent parasitic adhesins from getting too close to the reticulocyte membrane, which prevents the entry of the parasite, ”she said.
This discovery opens the door to potential prevention not only P. vivax malaria, but also P. falciparum malaria, another major cause of death in the world.
“Although this is a vivax study, we believe the implications are that a broadly neutralizing antibody could be created to target both P. vivax and P. falciparum malaria infections, ”said Associate Professor Tham.
Improve detection of recurrent malaria
Professor WEHI Ivo Mueller said that beyond understanding how antibodies can block infection, there is also a crucial need to understand the development of immunity and how this could be used to detect P. vivax infections in endemic populations.
“We are currently using this information to develop diagnostic tests that will be used in the field to identify and treat people with a hidden Vivax infection in their liver and spleen.” This is a key step towards eliminating malaria, preventing those infected silently from re-infecting their communities. ,” he said.
This work was made possible with funding from the National Board of Health and Medical Research, the European Research Council and the Government of Victoria.
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