Malaria vaccine delivered by mosquito's bite

A new malaria vaccine has been trialled in which subjects were administered the vaccine by 1000 mosquito bites
26 August 2022

Interview with 

Sean Murphy, University of Washington

Mosquito biting

A mosquito biting a finger

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This week researchers at the University of Washington have published some encouraging data from a clinical trial they’ve been running using a live malaria vaccine that they’ve developed. Long term, they’ll make the vaccine in a test tube, but for now, while they work out its feasibility and effectiveness, they’re testing it by using mosquitoes themselves to vaccinate people! Sean Murphy…

Sean - The world needs a very highly effective malaria vaccine and, while a new vaccine was approved late last year, the efficacy of that vaccine is not as high as we would like. So one of the most successful ways to make vaccines is to take the organism that causes the disease and to weaken it and turn it into a vaccine. People have been trying to do that for malaria for actually decades and this study showed that this could be a very effective approach.

Chris - So how have you weakened it?

Sean - Well, the DNA of the malaria parasite has more than 5,000 genes. And, leading up to this study, some of the researchers involved figured out some genes that were really important for the parasite to survive in your liver. And if they made changes to the DNA, so that those genes no longer worked, they found that now the parasite couldn't make it through the liver stage. And therefore couldn't go on to cause like disease that we would see with a normal parasite.

Chris - How did you test this then? Because, obviously malaria is transmitted by mosquitoes normally, so how would you vaccinate a person?

Sean - So in this study, we actually use the mosquitoes as tiny little flying syringes because the form of the parasite that serves as the vaccine, we can only right now make it in mosquitoes. And what we know is that if people get about a thousand mosquito bites with these weakened parasites, they can end up being protected against the later 'challenge' with mosquitoes that carry the regular old malaria parasite.

Chris - How on earth do you persuade people to get a thousand mosquito bites?

Sean - Yeah. Well, first of all, it's not a thousand in one sitting, let me be clear about that. The bites were administered about 200 bites per sitting, and some people had some pretty intensely itchy arms after that. And so we pay a lot of attention to how to limit that. But, within a matter of a few days, usually that went away. But that was our strategy for vaccinating and the volunteers were really wonderful and generous of their time.

Chris - And what happened when these people got these hundreds of mosquito bites, did they mount a malaria response?

Sean - It's very clear that the people definitely mounted an immune response. We can see that people are making antibody responses against the parasite, but we also know that there are probably immune responses that we cannot measure when we just take blood from a vein. And that's why the challenge model is so important for us to actually be able to measure whether we succeeded or didn't with the vaccine.

Chris - And when you say challenge model, this is you coming along later and physically trying to infect people with malaria for real, to see if they're protected by the prior exposure to the weakened vaccine strain.

Sean - Yeah, that's correct. And we challenge them with usually five mosquito bites. We follow them for the emergence of the parasites in their blood, which would indicate that whatever we were trying to protect against in the liver did or did not work. So someone who had a good vaccine response wouldn't have the parasites emerging in their blood ever because they would be completely protected and we can follow that really closely.

Chris - And is that what you saw?

Sean - So what we saw in this study was that half of the vaccinated people were completely protected against infection. It's a very high bar to achieve complete protection against because even just one of the parasites that comes from the mosquito can go on to ignite the blood stage infection later on. So 99% reduction is not enough. You really have to achieve a hundred percent eradication of the parasite in your liver. What this study tells us is that this genetically attenuated parasite approach is actually quite promising. And the reason that we're not disappointed that we didn't get a hundred percent protection, is that we know that if we put the vaccine in by needle and syringe, it's likely to have a higher rate of protection. And that's because every time we give mosquito bites, the vaccine is to some extent stopped in its tracks right there in the skin. But if we give it by needle and syringe, it's likely that more of the vaccine will get to the liver. And if it gets to the liver, we think more of it will be able to do its purposeful role as a vaccine.

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