One Seattle morning, Carolina Reed sat in a room with nine other volunteers, each waiting to participate in a clinical trial for a new experimental malaria vaccine.

Reid’s turn came. She placed her hand on a cardboard box filled with 200 mosquitoes, covered with netting that kept them out but still allowed them to bite. “Literally a container for Chinese food,” she recalls. Then a scientist covered her hand with a black cloth, because mosquitoes like to bite at night.

Then the feeding frenzy began.

“My whole arm was swollen and bruised,” Reid says. “My family laughed and said, ‘Why did you subject yourself to this?'” And she didn’t just do it once. She did it five times.

You might be thinking – this is a joke, right?

Swelling of Reid's arm after being bitten by 200 mosquitoes at once to receive an experimental malaria vaccine.

Swelling of Reid’s arm after being bitten by 200 mosquitoes at once to receive an experimental malaria vaccine.

But no. “We treat the mosquitoes like 1,000 little flying needles,” said lead author Dr. Sean Murphy, a physician and scientist at the University of Washington in Seattle. Science Translational Medicine It was released on August 24, detailing the vaccine trials.

The insects directly transmit malaria-causing Plasmodium parasites that have been genetically modified to prevent people from getting sick. The body still makes antibodies against the weakened parasite so it gets ready to fight the real thing.

To be clear, Murphy does not plan to use mosquitoes to vaccinate millions of people. In the past, mosquitoes have been used to deliver malaria vaccines for clinical trials, but not routinely.

He and his colleagues went this route because it is expensive to make an injectable parasite. Parasites mature in mosquitoes, so at this conceptual stage – as they are called preliminary experiments – it makes sense to use them for breeding.

“You’re going old school with this,” he says. Dr. Kirsten Lyke, a physician and vaccine researcher at the University of Maryland School of Medicine who was not involved in the study. “All things old shall become new.”

She calls the genetically modified live parasite a “total game changer” for vaccine development.

This type of vaccine is not yet ready for prime time. But a small trial of 26 participants showed that the modified parasites protected some participants from malaria infection for a few months.

Murphy believes this approach could one day lead to a more effective vaccine. The world’s first malaria vaccine, the RTS,S vaccine from drugmaker GlaxoSmithKline. The World Health Organization approved it last year, but the effectiveness rate is only 30-40%.

Mosquitoes and malaria – toxic relationship

When Reid joined the trial in 2018, she was looking for a job. “The first thing that caught my eye was the money,” she says — a $4,100 fee for participants. But when she talked to friends with malaria, she found a different inspiration. She said at that point it was no longer about money – although it was still good – instead of being part of important research.

Color microscope image of malaria parasite <em data-stringify-type="ሰያፍ"> Plasmodium sp.</em>(green), red blood cell (red) staining.  Infected with malaria <em data-stringify-type= ይተላለፋል"ሰያፍ"> Anopheles</em>Mosquitoes for people.  The parasites attack the liver, then move into the bloodstream.” width=”880″ height=”542″ srcset=”×1890 +0+1048/resize/1760×1084!/quality/90? ://×1890+0+1048/resize/880×542!/quality/90/?url=https%3A%2F%2Fmedia.npr .org%2Fassets%2Fimg%2F2022%2F09%2F21%2Fsciencesource_ss2100645_custom-023cd6ebc9e580094f0180d97d78664aee683ac0.jpg” loading=”lazy” bad-src=”data:image/svg+xml;base64,PHN2ZyB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHZlcnNpb249IjEuMSIgaGVpZ2h0PSI1NDJweCIgd2lkdGg9Ijg4MHB4Ij48L3N2Zz4=”/></p>
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Dr. Tony Breen/Science Source

Color microscope image of malaria parasite, Plasmodium sp. (green), red blood cell contamination (red). Malaria is transmitted from the disease. Anopheles Mosquitoes for people. Parasites attack the liver, then move into the bloodstream.

Malaria parasites live in the salivary glands of Anopheles mosquitoes. The disease is most common in Africa, where warm climates are ideal for pest growth. People get malaria through the bite of an infected mosquito. Infected people can transmit the malaria parasite to mosquitoes that bite them, and the cycle of infection continues.

Countries fight malaria with mosquito nets, insecticides, Antimalarial drugs And even leaving Genetically modified mosquitoes They cannot bite or lay eggs.

Even with those measures, scientists estimate more than 240 million cases of malaria and 600,000 deaths a year – which is why vaccines are needed.

A promising start – but room for improvement.

Murphy thinks this experimental vaccine should stimulate a stronger immune response than the WHO-approved RTS,S vaccine because it uses a completely inactivated parasite. RTS,S targets “just one of over 5,000 proteins” that the parasite produces, he said.

Others have tried to make a malaria vaccine from disarmed parasites. What’s new is that this team has disarmed them with CRISPR – a pair of highly advanced molecular scissors that can cut DNA.

To test how well the approach would work, Reid and the other participants had to get another round of mosquito bites — this time containing the real malaria parasite.

Of the 14 participants exposed to malaria, seven – including Reid – succumbed to the disease, meaning the vaccine was only 50% effective. For the other seven, the wait lasted no more than a few months.

“When they told me I had malaria, I cried because I had developed such a close relationship with the nurses,” says Reid. She wanted to continue with the exams, but the infection disqualified her. She was given medicine to cure her malaria and sent home..

“We obviously think we can do better,” he says. Stephen CaptThe study’s author and parasitologist at the University of Washington, Seattle, and the Seattle Children’s Research Institute. He and Murphy hope to improve their team’s effectiveness by injecting the vaccine into syringes instead of using mosquitoes. A higher initial dose may lead to greater protection over a longer period of time.

Like, some scientists think that using a slightly more mature version of the parasites included in this vaccine may give the body more time to develop an immune system. The team is working on that approach, Cappe says.

If future trials are promising, there are other questions to consider. For starters: How much does this type of vaccine cost? The scientists are collaborating with a small company called Sanaria To produce improved parasites. Cappe says that increasing production capacity to increase manufacturing requires investment.

As for Reid, her experience was so positive that she went on to participate in clinical trials for the bird flu vaccine and Moderia’s Covid-19 vaccine. She says she will continue to enroll in vaccine clinical trials “for the rest of my life, really.”

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