In a new trial, scientists used mosquitoes to deliver a malaria vaccine

One morning in Seattle, Carolina Reed They sat in a room with nine other volunteers and waited to participate in a clinical trial to test a new malaria vaccine. When it was Reed’s turn, he placed his arm over a cardboard box filled with 200 mosquitoes. The box was covered with lace; So that mosquitoes don’t run away and at the same time they can bite. Then a scientist covered his arm with a black cloth; Because mosquitoes like to bite at night. The mosquitoes started sucking Reed’s blood like crazy.

“My whole forearm was swollen and blistered,” Reid says. My family would laugh and ask me, why are you exposing yourself to such a thing? He didn’t do it just once; Rather, he repeated it five times. You might think this is a joke; But it is not. the doctor Sean Murphy, is a physician and scientist at the University of Washington and the author of an article published in the journal Science Translational Medicine that describes the vaccine trial. “We use mosquitoes as little flying syringes,” he says.

Mosquitoes transmit Plasmodium parasites that cause malaria; But the mosquitoes used in this part of the experiment were genetically modified so as not to cause people to get sick. The body continues to make antibodies against the weakened parasite; Therefore, it prepares to deal with the real parasite.

The participant's arm in the trial after a mosquito bite / arm swelling

Reed’s arm swelling after 200 mosquitoes bit him simultaneously to inject the experimental malaria vaccine into his body.

Murphy does not intend to use mosquitoes to vaccinate millions of people. In the past, mosquitoes have been used to deliver malaria vaccines in clinical trials; But this is not common. He and his colleagues followed this path; Because it is expensive and time-consuming to make a parasite formulation that can be injected into the body with a needle. Parasites mature inside the body of mosquitoes; So at this stage, proof of concept of using them for vaccine delivery is reasonable.

the doctor Kristen Like, a physician and vaccine researcher at the University of Maryland School of Medicine, calls the use of genetically modified live parasites revolutionary in the field of vaccine development. This type of vaccine is not yet ready for widespread use; But a small trial of 26 participants showed that the modified parasites protected several participants against malaria infection for several months.

Murphy believes that this approach could lead to a vaccine that is more effective than the world’s first malaria vaccine. The said vaccine is called RTS,S and it was made by GlaxoSmithKline. The World Health Organization approved this vaccine last year; But its efficiency rate is 30 to 40 percent.

The toxic connection between mosquitoes and malaria

Reed was looking for work when he joined the trial in 2018. “The first thing that caught my attention was the money,” he says. Participants were paid $4,100; But when he talked to his friends who had contracted malaria, he found another motivation. He said that money was no longer his main goal at that time; Rather, participating in this research became more important for him.

Malaria parasites live in the salivary glands of Anopheles mosquitoes. This disease is more common in Africa, where the warm climate is suitable for the growth of the parasite. Humans get malaria from the bite of an infected mosquito. Infected people transmit the malaria parasite to mosquitoes that bite them, and the cycle of infection continues.

Countries try to control malaria by using mosquito nets, insecticide sprays, antimalarial drugs, and even by releasing genetically modified mosquitoes that cannot bite or lay eggs. Even with these measures, scientists estimate that more than 240 million cases of malaria and more than 600,000 deaths occur annually; Therefore, it is necessary to develop a vaccine for this disease.

Malaria parasite

Color microscopic image of a malaria parasite (green) infecting a red blood cell (red). Malaria is transmitted to humans from infected Anopheles mosquitoes. This parasite infects the liver and then enters the blood.

It has been a promising start; But there is still room for improvement. The reason Murphy thinks the new experimental vaccine should elicit a stronger immune response than the RTS,S vaccine is because the new vaccine uses the whole parasite, which has been weakened. The RTS,S vaccine targets only one of more than 5,000 proteins that the parasite produces.

Others have tried to make a malaria vaccine from the disarmed parasites. The new thing is that this team has removed this pathogenic ability of the parasite with the help of CRISPR. CRISPR is a very precise molecular scissors that cuts DNA.

To test how the approach worked, Reid and the other participants had to receive another round of mosquito bites, this time containing real malaria parasites. Of the fourteen participants exposed to malaria, seven, including Reed, developed the disease, meaning the vaccine was only 50 percent effective. For the other seven, the protection did not last more than a few months.

“When they told me I had malaria, I cried,” says Reed. Because I had developed a close relationship with the nurses.” He wanted to continue the trials; But his infection made him unable to attend. He received medication to clear up his infection and was sent home.

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Stephen Kapp, study author and parasitologist at the University of Washington in Seattle, believes they can improve their approach. By putting the vaccine in a syringe instead of using mosquitoes, he and Murphy hope to deliver enough doses to volunteers to increase efficacy. A higher initial dose can provide greater protection for a longer period of time.

Some scientists think that using a more mature version of the parasite than the ones used in the vaccine gives the body more time to mount an immune response, Like said. According to Cap, the research team is working on this approach.

If future trials prove promising, there are other questions that need to be answered. For example, how much will this type of vaccine cost? The scientists are working with a small company called Sanaria to produce the modified parasites. Kapp says that increasing the production capacity requires investment to increase the scale of production.

For Reid, the experience of participating in the trial was so positive that he also participated in the clinical trial of Moderna’s avian flu vaccine and covid-19 vaccine. He says that he will continue to participate in vaccine clinical trials.

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