Harnessing power of white blood cells could be key to an effective malaria vaccine

 For nearly 40 years a highly protective vaccine to fight malaria has eluded researchers, but a replacement Australian study hopes to assist change that.

Key points:

Malaria may be a life-threatening disease, but it's preventable and curable

The most advanced malaria vaccine has shown only modest efficacy of 26-36 percent 

Research shows a replacement role for antibodies harnessing the killing power of white blood cells

A team publishing within the journal Nature Communications reports they need to uncover a previously unknown role played by antibodies during the first stages of infection.

"We think we have a replacement thanks to checking out the matter and a replacement thanks to attacking the infection and to urge that vaccine protection much higher," said researcher James Beeson of the Burnet Institute.

Professor Beeson and his colleagues have found antibodies that will harness the facility of white blood cells called neutrophils to kill the plasmodium during initial infection within the blood.

And targeting infection at this stage may hold the key to simpler vaccines, the researchers said.

But how does malaria make people sick, and the way does this new approach hope to beat a number of the challenges in developing a vaccine against it?

Malaria transmitted by infected female mosquitoes

Malaria may be a life-threatening disease, but it's both preventable and curable.

According to the planet Health Organization's latest world malaria report, released last November, 229 million cases of the disease were reported in 2019 and 409,000 died from it.

The infection is caused by parasites, transmitted to people through the bites of infected female mosquitoes.

After the malaria microorganism gets into the skin, it enters the bloodstream then the liver, Professor Beeson explains.

It's there that the parasite multiplies, invading red blood cells and multiplying until the cells burst, releasing more parasites into the bloodstream that continue attacking red blood cells.

The complexity of creating a vaccine

Nicole Lawrence, a senior research officer with the University of Queensland's Institute for Molecular Bioscience, says the most important challenge for designing malaria vaccines is that the parasite goes through different life cycles after entering the body.

It enters the body as a sporozoite, but transforms when it goes into the liver when it's released from the liver cells, and again when it's reproducing itself within the blood.

And at each stage the parasite has tremendous diversity in how it appears, making it hard to focus on.

"You've quite got this chameleon parasite that keeps changing what it's like on the surface … it's pretty clever," Dr. Lawrence said.

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"Therefore finding one vaccine that's getting to protect against all possible parasites that you simply might be exposed to goes to be a challenge."

Professor Beeson says the parasite itself also features a lot more proteins than SARS-CoV-2, the virus which causes COVID-19.

"It's a vastly more complicated organism and it's vastly harder to seek out an immune reaction, which can just knock it off and block it," he said.

The best efficacy for a malaria vaccine so far is 26-36 percent in babies and young kids.

"We need something that's getting to rise up thereto 70 to 80 percent [vaccine efficacy rate] or higher," Professor Beeson said.

Justin Boddey, malaria laboratory head with the Walter and Eliza Hall Institute of Medical Research, said protection from existing vaccines wasn't long-lasting.

"We do not have an honest malaria vaccine."

'Two-pronged attack' against malaria

Professor Beeson said most successful vaccine approaches so far had focused on preventing infection from entering the liver.

But he and colleagues checked out whether human immune cells could launch the attack on malaria from the primary moment the infection was transmitted by mosquito bite; before it had time to urge to the liver and begin multiplying.

"What we found is yes, that's possible, and it's quite a sort of a two-pronged attack," Professor Beeson said.

The attack involves antibodies (proteins that the system makes to focus on a pathogen) and a particular sort of white blood corpuscle called neutrophils, the researchers found.

Professor Beeson explained that the antibodies "coat" the parasite, then the neutrophils attack it.

"The cell type that did the majority of the add killing malaria, neutrophils, happens to be the foremost abundant white blood corpuscle in our blood," he said.

Dr. Lawrence said the study challenged the normal understanding of what antibodies did, which was only to bind to the pathogen.

"The antibodies that they are describing during this paper are literally targeting and recruiting the remainder of the military [to attack the disease]," she said, adding it might be important to think about this type of impact when creating vaccines.

Professor Beeson agreed.

"The important thing is to harness the [antibody-neutrophil] mechanism to urge vaccines to act much earlier, and hopefully clear parasites before they need an opportunity to urge to the liver," he said.

The researchers identified regions of a serious malaria protein that would be a target for future vaccines or modifications of existing ones.

Dr. Lawrence said it wasn't a case of simply "throwing out the baby with the bathwater" by abandoning the present vaccine candidates.

"This progress is basically exciting progress, and this is often getting to help in future, driving towards making simpler vaccines," she said.

Dr. Boddey was also optimistic about the longer-term of vaccine development.

"There are exciting times ahead needless to say," he said.

Professor Beeson said the complexity of malaria as a disease, plus a scarcity of investment had delayed progress in developing an efficient vaccine since research started within the 1980s.

"You need tons of cash to actually target a problem like malaria."

Dr. Lawrence agreed research had been hampered by a scarcity of investment.

"If it had been killing a special population within the world, we might have had a cure by now," she said.

According to the WHO, Africa was home to 94 percent of all malaria cases and deaths in 2019.

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