US researchers say a new malaria vaccine candidate stops the parasite mid lifecycle | Science| In-depth reporting on science and technology | DW | 22.05.2014
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US researchers say a new malaria vaccine candidate stops the parasite mid lifecycle

Most malaria vaccine candidates work by preventing parasites from entering human red blood cells. A newly discovered antibody takes a different approach: it traps the parasites inside the cells.

If you can't keep them out - try trapping them in.

That's the idea behind a new discovery made by US-based malaria researchers.

Their promising malaria vaccine candidate is an antibody, which acts against a protein called PfSEA-1.

Malaria parasites need the protein so they can get out of the human red blood cells once they have replicated there.

This rupture is often accompanied by a fever attack in the patient as more infectious parasites enter the blood stream.

But while identifying the gene PfSEA-1 and its corresponding protein in the most lethal malaria parasite Plasmodium falciparum, researchers at the Rhode Island Hospital in Providence have found that when this protein is blocked by an antibody, the parasite's life cycle stops mid-flow.

"We are sort of trapping the malaria parasite inside the burning house," study leader Jonathan Kurtis of Rhode Island Hospital says. "It can't go anywhere. It can't do any further damage."

Breaking the cycle

Malaria parasites go through a complicated life cycle inside the human body.

You get bitten by a mosquito and the parasite enters your blood stream. It then reproduces in your liver cells. Then, it multiplies inside red blood cells - until the one parasite has become 8, or as many as 24.

Before the red cells erupt, this form of the malaria parasite is known as a schizont.

Infographics: life-cycle stages of malaria parasites

Life cycle of a malaria parasite: from mosquito to liver cells to blood cells and back into the mosquito

As the researchers report in the journal "Science", every schizont produces the protein PfSEA-1 - hence the name: Plasmodium falciparum schizont egress antigen-1.

Human relevance

Antibodies against PfSEA-1 can prevent malaria parasites from reproducing in the lab, Kurtis and his colleagues show. Moreover, injected as a vaccine, these antibodies can prolong the life of lab mice when they are infected with a very deadly form of rodent malaria, which resembles a form of malaria that is usually fatal in small children.

Kurtis says no vaccine candidate has ever been able to protect mice from this lethal disease.

But his promising substance occurs naturally in humans: it makes them resistant to malaria.

"What really distinguishes our work is: we began with human beings," Kurtis says. "While a portion of the research was conducted in mice, the actual vaccine discovery experiments were performed using human samples - so we believe the result will effectively translate to humans."

Electron-microscopy image of malaria parasites inside a red blood cell Photo: J. Kurtis

Malaria parasites are trapped inside a human red blood cell

Antibodies make children resistant to malaria

The researchers studied 785 children in Tanzania, all living in a high-risk region.

Some of the children had developed a resistance to malaria when they were about two years old: they carry the parasite, but don't get sick.

"We performed in the lab what I call DNA gymnastics," says Kurtis. "We used some fancy molecular biology to identify parasite genes [and] parasite proteins that are only recognized by antibodies in the resistant kids, but not by antibodies in the susceptible kids."

They found PfSEA-1.

After performing experiments in the lab and in animals, the researchers went back for more field experiments in Tanzania and discovered what Kurtis describes as a "shocking" result.

"Children who had detectable antibodies to this antigen (protein) never got severe malaria - there were zero cases."

In another study involving a group of boys and men in Kenya, they found that humans with these antibodies have fewer malaria parasites in their blood.

"Our next destination is a vaccination trial in monkeys, followed by phase-one-trials in humans," Kurtis says.

Their findings could be central to an effective vaccine.

doctors in the lab, Albert-Schweitzer clinic in Gabon (Photo: Gaia Manco)

Researchers around the world are working on numerous potential malaria vaccines

But is one vaccine enough?

Thomas Jacobs, malaria researcher at the Bernhard Nocht institute for Tropical Medicine in Hamburg, says the results are "exciting" and "spectacular".

"It seems very convincing," says Jacobs, before adding that we have yet know for sure whether the method will work as a vaccine for humans in the field.

Around the world, researchers are currently investigating about a hundred different malaria vaccine candidates.

The most advanced candidate is RTS,S. It is being developed as a vaccine for children by the pharmaceutical company GlaxoSmithKline, together with universities and research institutes, and with funding from the Bill and Melinda Gates foundation. The RTS,S vaccine targets the liver cells and prevents the malaria parasites from reproducing.

A phase-III-trial has just been completed.

RTS,S could enter the market as soon as it is approved by the relevant health authorities.

However, the vaccine has an efficiency of just about 50 percent - half of all the children vaccinated will still get sick - and may die as a result. A recent study has even found its efficiency drops after four years.

So it is likely that we'll need more than one malaria vaccine, Jacobs says.

In fact, we may need to combine several substances to target different life cycle stages of the parasite.

"You might then get a form of protection that isn't lost as soon as the malaria parasite develops a mutation in the protein that is targeted by one particular vaccine."

In that case, there would still be a second vaccine making sure that the mutated parasite is unable to survive and multiply.

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