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Scientists Found One of the Most Promising Malaria Vaccine Targets to Date

Scientists Found One of the Most Promising Malaria Vaccine Targets to Date. Science & Technology World Website

In spite of a decade of intense research, we still don't have a commercially available vaccine for malaria.

While a candidate vaccine is being piloted next year, scientists have found a potentially more promising target in the bridge malaria makes with our red blood cells, which could lead to a more effective, cheaply made vaccine.

There are half a dozen species of the plasmodium parasite responsible for causing malaria in humans, with P. vivax and the extra nasty P. falciparum being the two most common. They are all spread through the bite of infected mosquitos, affecting 97 countries and territories world-wide. 

In 2015, plasmodium made 212 million people sick and took roughly 430 thousand lives, mostly children under the age of 15.

If these numbers seem big, we've seen a marked improvement over the past 15 years. Mosquito netting and insecticides have helped reduce the number of cases since 2000 by 22 percent, while fatalities have been halved.

The World Health Organisation's Global Technical Strategy for Malaria has set a goal to wipe the disease out completely in at least 10 countries by 2020, and reduce cases by 40 percent in all other countries where the disease is endemic.

Yet we still have far to go if we're to eradicate what is considered to be one of the deadliest diseases that's threatening our modern world.

A powerful weapon in the fight against the parasite would be a cheap, stable vaccine which could be distributed through the world's remote, poorer populations.

One promising candidate is the RTS,S vaccine - also known as Mosquirix - which will be piloted in Africa next year. If it works as hope, it could cut down infections in young children by half.

Yet the search is still on for even more effective tools capable of providing solid immunity against the blood-invading parasite.

With that in mind, a team of researchers at the Wellcome Trust Sanger Institutehas turned its focus a chemical the pathogen uses to link itself to the host's red blood cells. 

The molecule, dubbed RH5, was found in previous research to connect a red blood cell receptor called basigin, somehow sticking the two cells together. Another two proteins, CyRPA and RIPR, were found to form a complex with RH5. The details, however, were still hazy.

Now the researchers have discovered precisely how this process works.

Scientists Found One of the Most Promising Malaria Vaccine Targets to Date. Science & Technology World Website

As the plasmodium secretes the RH5 protein, a receptor on its surface called P113 grabs hold, allowing it to anchor itself to a red blood cell long enough to slip inside. The other two proteins were found to stick to one another, with CyRPA then connecting with a specific spot on RH5.

The research revealed just a small area of RH5 was used to connect to the plasmodium receptor, hinting at the possibility of producing a 'blocker' easily and cheaply.

One of the team members, Julian Raynor, explained how this is exciting news for making a cost effective multi-component vaccine.

"We knew both proteins were essential for invasion but this is the first time anyone has seen the interaction between RH5 and P113 and showed that they work together.

In theory, an antibody that blocked P113 could stop RH5 binding and so prevent the parasite from gaining entry to red blood cells. This makes the P113 protein another good vaccine target."

The RH5 protein complex is the vital link between the malarial parasite and our blood cells. Finding ways to target it with a vaccine could lock the pathogen out of our bodies, putting us one step closer to a malaria-free future.

This research was published in Nature Communications.

This malaria drug is having an amazing effect on brain cancer patients

This malaria drug is having an amazing effect on brain cancer patients. Science & Technology World Website

There's new hope for improved brain cancer treatments after scientists noticed unexpectedly positive effects coming from an unlikely source – a drug normally used to treat malaria.

The anti-malaria drug chloroquine has now been used as a last resort on three brain cancer patients, and in each case, it seems to have overcome the cancer's resistance to traditional treatments.

Chloroquine appears to break down the defences that tumours develop in response to cancer-fighting drugs by effectively 'resetting' their vulnerability to treatment.

"We have treated three patients with the combination, and all three have had a clinical benefit," says paediatric oncologist Jean Mulcahy-Levy from the University of Colorado.

"It's really exciting - sometimes you don't see that kind of response with an experimental treatment."

One of the patients is 26-year-old Lisa Rosendahl, who was previously given just a few months to live. The aggressive glioblastoma in her brain had become resistant to chemotherapy and other targeted treatments.

Rosendahl was eventually put on a cancer inhibitor called vemurafenib, but as often happens with that particular drug, the tumour in her brain soon adapted to become resistant to it, too.

That led the staff working on Rosendahl's case to try a different approach - targeting a separate cellular process called autophagy.

Autophagy is a normal process inside the body whereby dead or damaged cells are removed and recycled to make way for fresh ones. Taken from Greek, the term literally means "to eat oneself", and it's an important way of detoxifying and repairing the body.

The trouble is, tumours sometimes use autophagy to stay healthy, leveraging cellular recycling to withstand the stress that drugs put them under. Rosendahl had a type of cancer that was especially dependent on the process, due in part to a genetic mutation called BRAFV600E.

Fortunately, chloroquine is known to inhibit autophagy, so with that in mind, Mulcahy-Levy and her team decided to give the drug a try as a last-ditch effort to combat the tumours - by combining it with vemurafenib.

"Miraculously, [Rosendahl] had a response to this combination," says Mulcahy-Levy. "Four weeks later, she could stand and had improved use of her arms, legs, and hands."

This malaria drug is having an amazing effect on brain cancer patients. Science & Technology World Website

The chloroquine didn't remove the tumour, but it did weaken the cancer's defences enough to get the vemurafenib drug working again to do that on its own, and now Rosendahl's quality of life is improving.

Only three patients have been given the treatment so far, and not every type of cancer relies so much on autophagy, so until it's been tested on a much larger and diverse sample, it's too soon to tell if it will have similar effects on other patients.

But the team says a wider clinical test could be rolled out quickly, because chloroquine is already approved as a safe anti-malaria drug by the US FDA (Food and Drug Administration).

The researchers hope that future studies will reveal other cancers where this treatment could be effective. 

"It makes me feel really lucky to be a pioneer in this treatment," says Rosendahl. "I hope it helps and I hope it helps people down the road. I want it to help."

The latest findings have been published in eLife.

With malaria, bugs matter more than bites

With malaria, bugs matter more than bites. Science & Technology World

In the battle against malaria, science is taking a true 360-degree approach. There aretechniques that render mosquitoes immune to the parasites (and give them oddly glowing red eyes) so that they can't pass the disease on to humans; a breath test to diagnose the disease in humans; and an effort to make malaria-carrying mosquitos infertile. But oddly, according to researchers at Imperial College London, one major component to malaria research has been absent – comparing the number of parasites transmitted in a mosquito's bite to disease transmission, rather than just looking at the number of bites themselves. So that's exactly what they set out to study.

And sure enough, it turns out that parasite concentration in a mosquito's blood is a much more important factor in malaria transmission than being bitten multiple times, which might explain why the one and only registered malaria vaccine – RTS,S – only worked some of the time in trials.

It seems that some mosquitoes are simply "super infected" and those are the ones that are likely to pass along malaria.

"It is surprising that the relationship between parasite density and infectiousness has not been properly investigated before, but the studies are quite complex to carry out," said study co-auhtor Dr Andrew Blagborough, from the Department of Life Sciences at Imperial.

"Researchers have long wondered whether the more malaria parasites in a mosquito's mouthparts, the more likely they are to infect a host with the disease," said Dr Morvern Roberts, programme manager for global infections at the Medical Research Council who funded the research. "No one has been able to demonstrate this until now but the authors of this paper have shown that this is the case in both mouse models and in humans."

In their tests, the researchers subjected sedated mice to bites from mosquitoes with varying levels of parasites in their bodies and found that only the mosquitoes with lots of parasites could transmit the disease. They then moved on to human volunteers and saw the same thing. Study co-author Dr Thomas Churcher, from the MRC Centre for Outbreak Analysis and Modelling at Imperial, told New Atlas that at this time, however, the precise numbers of parasitic transmission are a bit of a mystery.

"In this study we only tested a single dose of the vaccine and the precision of our measure of parasite dose is quite uncertain," he told us.

"What we do know is that in this study only volunteers given a vaccine who were bitten by mosquitoes with more than 1000 parasites in their salivary glands following blood-feeding developed infection," he continued. "This suggests that the vaccine was providing protection against lightly infected mosquitoes but not heavily infected mosquitoes. This is similar to what we saw in mice. Unfortunately we do not know exactly how many parasites were injected into the person as this is currently impossible to tell in human volunteers."

Churcher adds, though, that having this new knowledge and being able to focus on parasitic concentrations rather than on number of bites, as groups such as the World Health Organization currently do, could help dramatically advance the research in the field.

"Vaccine development has come a long way, and this new insight should help future vaccine studies to be tested more rigorously," he said. "However, in the end, it is unlikely that one magic bullet will eradicate malaria, and we should continue to seek and apply combinations of strategies for reducing the burden of this disease."



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