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Shutting the door on Malaria offers new vaccine hope

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December 18, 2013

NTU Prof Peter Preiser and scientist Dr Annie Gao

NTU Prof Peter Preiser and scientist Dr Annie Gao

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A new discovery by scientists from Singapore’s Nanyang Technological University (NTU) holds promise for the development of a Malaria vaccine. The result of five years research, the breakthrough is based on the ability to block the invasion of red blood cells by the deadly parasite.

According to the World Health Organization, around half the world’s population, or 3.3 billion people, are at risk of malaria infection and around 627,000 fatalities were recorded in 2012.

No vaccine for Malaria currently exists, though scientists around the world are continuing to work toward that goal.

Unlike treatments that work by building up antibodies, the NTU research takes a different approach.

Red blood cells are targeted by the Malaria parasite, Plasmodium falciparum (P. falciparum), which then transport the virus to the host’s liver where it can mature and reproduce causing fever, headaches, nausea and in some cases death.

The process discovered by the NTU team prevents the parasite from binding with red blood cells in the first place. This disruption is achieved through blocking calcium signalling between the parasite and the host cell.

Of particular interest are two types of proteins, erythrocyte-binding-like proteins (EBLs) and reticulocyte-binding protein homologues (RHs). Both are used by P. falciparum early in the invasion process where specialized organelles known as rhoptries and micronemes bind with the host cell. This is followed by penetration of the host cell wall resulting in successful invasion. The research has shown that by disrupting the binding process the parasite can be stopped.

Monoclonal antibodies, identical antibodies produced by cloned immune cells, were used to disrupt the RH and EBL proteins. This was achieved by interrupting calcium signalling between PfRH1 (an RH protein identified in P. falciparum) and the host cell. It was found that this disruption also prevented engagement and discharge from EBL protein EBA175, which completely stopped the binding process.

“What we have identified is a region of the Malaria parasite which it uses to attach to a healthy blood cell then pushes itself into the cell,” says lead scientist Professor Peter Preiser.

“To prevent this invasion, we developed antibodies which can interfere with this invasion process. So imagine the parasite has the key to unlock a door to the red blood cell, but we muck the key up, so no matter how hard the parasite tries, the door just refuses to open,” he said.

The development of high-throughput fluorescence scanning was critical to achievements of the NTU researchers. This new technology allowed the team to quickly identify antibodies that were effective in preventing the malaria parasites from invading the red blood cells. While the study has been ongoing for the past five years the development of this new screening assay allowed the characterization of parasite signalling to be carried out much more rapidly than by conventional methods.

Prof Preiser believes the breakthrough could be instrumental in paving the way towards eradicating Malaria in the long run.

A paper detailing the research was recently published in the journal Nature Communications.

Source: NTU

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