One morning in Seattle, Carolina Reid was sitting in a room with nine other volunteers, each waiting to participate in a clinical trial of a new experimental malaria vaccine.
It was Reid’s turn. She put her hand on a cardboard box filled with 200 mosquitoes and covered with a net that keeps them inside but still allows her to bite. “Literally Chinese take-away” is how he remembers her. The scientist then covered her arm with a black cloth as mosquitoes like to bite at night.
Then the feeding frenzy began.
“My entire forearm is swollen and blistering,” says Reid. “My family laughed, asking,” Why are you giving up on this? ” And she didn’t just do it once. She did it five times.
Perhaps you are thinking – this is a joke, right?
But it is not. “We use mosquitoes as if they were thousands of little flying syringes,” explains University of Washington, Seattle physician and scientist Dr. Sean Murphy, lead author of an August 24 article in Science Translational Medicine detailing vaccine trials.
These insects provide live, malaria-causing Plasmodium parasites that have been genetically modified to prevent them from becoming sick. The body still produces antibodies against the weakened parasite, so it is prepared to fight the real stuff.
To be clear, Murphy has no plans to use mosquitoes to vaccinate millions of people. In the past, mosquitoes were used to deliver malaria vaccines to clinical trials, but this is not common.
He and his colleagues took this path because developing a parasite formula that can be delivered with a needle is costly and time consuming. The parasites mature inside mosquitoes, so at this stage of the proof-of-concept – as the early-stage trials are called – it makes sense to use them for birthing.
“They went old school with that,” says Dr. Kirsten Lyke, a physician and vaccine researcher at the University of Maryland School of Medicine, who was not involved in the study. “Everything old becomes new again.”
He calls the use of a genetically modified living parasite a “total game changer” in vaccine development.
Of course, this type of vaccine is not yet ready for release. But a small sample of 26 participants found that the modified parasites protected some participants from becoming infected with malaria for several months.
Murphy believes this approach could eventually lead to a vaccine that will be far more effective than the world’s first malaria vaccine, the RTS, S vaccine from drug manufacturer GlaxoSmithKline. The World Health Organization approved it last year, but its effectiveness is only 30-40%.
Mosquitoes and malaria – a toxic relationship
Reid was looking for a job when she joined the trial in 2018. “The first thing that caught my attention was the money,” he says, “$ 4,100 in payments to participants.” But when she spoke to friends who contracted malaria, she found another motivation. She said at this point it wasn’t about money anymore – although it was still nice – but being part of important research.
Malaria parasites live in the salivary glands of Anopheles mosquitoes. The disease is most common in Africa, where the warm climate favors the development of the parasite. People contract malaria from the bite of an infected mosquito. Infected individuals can transmit the malaria parasite to mosquitoes that bite them, and the infection cycle continues.
Countries are trying to contain malaria with mosquito nets, insecticide sprays, anti-malarial drugs, and even by releasing genetically engineered mosquitoes that cannot bite or lay eggs.
Even with these measures, scientists estimate that there are over 240 million cases of malaria and over 600,000 deaths annually – which is why vaccines are needed.
A promising start – but there is room for improvement
The reason Murphy believes this experimental vaccine should stimulate a stronger immune response than the WHO-approved RTS, S vaccine is because it uses an entire weakened parasite. As RTS says, S targets “just one of more than 5,000 proteins” that the parasite produces.
Others have tried to make a malaria vaccine from disarmed parasites. What’s new is that this team disarmed with CRISPR – a highly advanced pair of molecular scissors that can cut DNA.
To see how well this approach worked, Reid and the other participants had to perform another round of mosquito bites – this time containing a real malaria parasite.
Of the 14 participants who were exposed to malaria, seven – including Reid – became ill, meaning the vaccine was only 50% effective. In the case of the remaining seven, protection did not last longer than a few months.
“I actually cried when they told me I had malaria because I had such a close bond with the nurses,” says Reid. She wanted to continue trying, but the infection made her ineligible. She was given a drug for malaria and sent home.
“We think we can of course do something better,” says Stefan Kappe, research 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 vaccine effectiveness by putting it in syringes instead of using mosquitoes so they can get the correct dosage. A higher starting dose may lead to greater protection over a longer period of time.
Lyke says some scientists believe that using a slightly more mature version of the parasite than the one in this vaccine may give the body more time to prepare for an immune response. The team is already working on this approach, says Kappe.
If future trials are promising, there are other questions to consider. First things first: How much would this type of vaccine cost? Scientists are working with a small company called Sanaria to produce modified parasites. Kappe says increasing production capacity to scale up production will require investment.
As for Reid, her experience was so positive that she participated in clinical trials of the avian flu vaccine and the Moderna COVID-19 vaccine. She says she will continue to enroll in vaccine clinical trials “for the rest of my life, actually.”
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