Discovery may aid vaccine design for common form of malaria

January 09, 2014

A form of malaria common in India, Southeast Asia and South America attacks human red blood cells by clamping down on the cells with a pair of proteins, new research at Washington University School of Medicine in St. Louis has revealed.

The study provides details that will help scientists design better vaccines and drug treatments for the strain, Plasmodium vivax.

"More people live at risk of infection by this strain of malaria than any other," said senior author Niraj Tolia, PhD, assistant professor of molecular microbiology and of biochemistry and molecular biophysics. "We now are using what we have learned to create vaccines tailored to stop the infectious process by preventing the parasite from attaching to red blood cells."

The finding appears Jan. 9 in PLOS Pathogens.

The World Health Organization estimates there were more than 200 million malaria cases in 2012. The deadliest form of malaria, Plasmodium falciparum, is most prevalent in Africa. But P. vivax can hide in the liver, re-emerging years later to trigger new infections, and is harder to prevent, diagnose and treat.

Earlier studies had suggested that one P. vivax protein binds to one protein on the surface of red blood cells. Tolia's new study reveals that the binding is a two-step process that involves two copies of a parasite protein coming together like tongs around two copies of a host protein.

"It's a very intricate and chemically strong interaction that was not easily understood before," Tolia said. "We have had hints that other forms of malaria, including the African strain, may be binding in a similar fashion to host cells, but this is one of the first definitive proofs of this kind of attack."

Tolia suspects blocking any of the proteins with drugs or vaccines will stop the infectious process.

"For example, some people have a mutation that eliminates the protein on red blood cell surfaces that P. vivax binds to, and they tend to be resistant to the parasite," he said. "This is why this strain isn't prevalent in Africa -- evolutionary pressure has caused most of the populations there to stop making this protein."

Tolia also found evidence that other people with immunity to P. vivax have developed naturally occurring antibodies that attach to a key part of the parasite's binding protein, preventing infection.

"The parasite protein is very large, and human antibodies bind to it at many different points along its length," Tolia explained. "We have observed that the ones that are most effective so far are the antibodies that bind to the protein at the region highlighted by our new research."
-end-
This research was made possible by funding from the National Institute for Allergy and Infectious Diseases of the National Institutes of Health (NIH) (R01 080792), the Edward Mallinckrodt, Jr. Foundation, an American Heart Association postdoctoral fellowship, and a National Science Foundation Graduate Research Fellowship (DGE-1143954).

Batchelor JD, Malpede BM, Omattage NS, DeKoster GT, Heinzler-Wildman KA, Tolia NH. Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC. PLOS Pathogens, online Jan. 9, 2014.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.