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article imageEssential Science: Knockout blow to malaria by immune cells trap

By Tim Sandle     Oct 24, 2016 in Science
One way to stop malaria parasites from spreading around the body is to kill them in the liver. Researchers have found a way to trap malaria killing immune cells in the liver, so they can target the parasite effectively.
To achieve this, a research group have developed a vaccine that directly boosts immunity in the liver. The reason for focusing on this organ is because the liver hosts a key early stage in malaria parasite transmission.
Malaria is an infectious disease of humans (and other animals) caused by parasitic microbes of the genus Plasmodium; it is transmitted through a bite from an infected mosquito into the blood. Most forms of malaria produce dormant liver stage parasites. In the liver, the parasites infect the organ's building blocks, called hepatocytes. Here the parasites change form (metamorphosis) before entering the blood stream, which is when the symptoms of malaria are manifested. In addition, liver stages can reactivate and cause an occurrence of the disease months after the infective mosquito bite.
Glass representation of the parasite that causes malaria
Glass representation of the parasite that causes malaria
Luke Jerram
In the liver there are typically a low number of parasites (in the hundreds). By the time the parasites enter the bloodstream they number in the hundreds of millions. This makes the liver a logical target for anti-malaria treatment. This is not straightforward, since the low number of parasites actually makes them hard to detect. It is also difficult to differentiate parasites from the body’s hepatocytes.
Hepatocytes make up 70-85 percent of the liver's mass. The cells are involved with a number of important functions, including protein synthesis. This includes the proteins necessary for blood clotting (and which prevent a person from bleeding to death; those without these clotting factors are haemophiliacs – a genetic disease — and who need regular doses of blood product clotting factors, such as Factor VIII).
In the liver, malaria parasites enter hepatocytes and remain there for about seven days. During this time the parasites undergo a transformation and enter the bloodstream, where they spread around the body.
The malaria vaccine is aimed at young children -- the main victims of malaria -- and is being develo...
The malaria vaccine is aimed at young children -- the main victims of malaria -- and is being developed by the British pharmaceutical giant GlaxoSmithKline (GSK)
Tony Karumba, AFP/File
The body’s natural immune system can kill some of the parasites, but generally there are too many parasites and the parasites are too well hidden for the immune response to be effective. However, if a person survives malaria and is re-infected, then the immune system is more robust at dealing with the parasitic invaders. This is due to a class of immune cells called ‘memory cells’. These cells ‘recall’ the previous infection, identify it more quickly, and are more effective at killing the invader.
This ability for the immune system to ‘remember’ an infection is the basis of the new vaccine. The vaccine prompts memory cells to form against a fake infection. This is achieved by exposing the immune system to an inactivated parasite (an antigen). The outcome is that the vaccinated person has immune protection should they ever encounter the real parasite. With the new malaria vaccine, the focus is on tissue-resident memory T cells.
The vaccine has been developed by Professor Thomas Gebhardt, Dr Laura Mackay and Professor Frank Carbone, also from The University of Melbourne at the Doherty Institute.
The effectiveness of the vaccine has been demonstrated in mice. Here a dual-stage vaccination step was performed. Stage one (called ‘priming’) involved attracting immune cells to the liver; the second stage was to ensure the immune cells stayed in the organ, by delivering the malaria antigen specifically to the liver. This means the immune cells could attack the parasitic organism rapidly and before the parasites move into the blood stream.
The outcome indicates that it should be possible to create a vaccine that produces immune cells that can take permanent residence within the liver. The vaccine remains at an early developmental stage. The next part of the development involves identifying equivalent antigens in the human parasite, comparable to those used for the mouse vaccine.
The research findings are published in the journal Immunity. The research paper is titled “Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.”
This article is part of Digital Journal's regular Essential Science columns. Each week we explore a topical and important scientific issue. Last week we looked deep into the solar system to assess which planetary moons might contain underground oceans (and whether life could exist within these oceanic lakes.) The week before we considered how nanotechnology is improving the material used to make bulletproof clothing for combat personnel.
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