AGS, malaria, and a potential treatment with Dr Peter Crompton

Yeah, that's really interesting.

Um, as just sort of a, a, a primer on malaria, can, can you remind me if, so you mentioned the idea of people being resistant, perhaps is, is it that they, there are humans who are resistant to malaria from the outset, or do you, do you develop almost like an induced resistance after having the infection over time.

So there are well-known genetic polymorphisms that are associated with protection from malaria.

So sickle cell trait is like the classic example where children are born with some resistance to experiencing severe disease when they become infected.

And so there are some people who are lucky enough to be born with some of these genetic polymorphisms that are protective.

But for most people, and even for people who have a genetic resistance, the immunity that we study is acquired over years and years of exposure.

And we know, and this is largely immunity against the blood stage.

So just real quick, the mosquito injects sporozoites into the skin and blood.

And within minutes, these go to the liver.

They replicate in the liver, not causing any disease or symptoms.

And after about a week, they pop out of the liver and start infecting erythrocytes.

And that's the stage at which people get sick and can die.

And so what we know from studies done in the 1960s is that if you passively transfer IgG antibodies from adults who have become resistant to getting sick when they get infected, and you give that to children who are sick with malaria, those antibodies control and kill off the blood stage parasites and their symptoms go away.

So we know... that after years and years of exposure, people can acquire antibodies that protect them from getting sick when they get infected.

What doesn't seem to happen is immunity that completely prevents infection altogether, if that makes

sense.

Thinking about the IgG response that is perhaps protective, what is that IgG against? What does it recognize?

Yeah, that's one of the key questions in malaria research.

And, you know, I think it's a broad set of proteins that protective antibodies target, among which are proteins that are necessary for the parasite to invade into a red blood cell, for example.

But it's probably not just one target, right? What we find is that that the profile of antibodies from one individual to the other is somewhat different, and it's probably a mix of antibodies against different proteins that ultimately confer some protection.

And where in the malaria story does alpha-gal show up?

Yeah, so...

Um, well, I, I guess what I'll point out again is that, um, there's not a lot of evidence that people acquire immunity to the first stage of the parasite.

This is the little, uh, it's called sporozoite.

This is what the mosquito injects into the skin and blood.