A vaccine against heart attacks
One in three people is destined to develop vascular disease - meaning furred-up arteries - that can cause heart attacks and strokes. But might it be possible to vaccinate people against this happening? Speaking with Chris Smith, Swedish heart specialist Jan Nilsson, at Lund University, explains how has a way of doing just that…
Jan - The disease I’m interested in atherosclerosis where fat accumulates in the arteries; this is mainly cholesterol. And we know that this cholesterol is being oxidised and that induces inflammation in the artery and the inflammation activates scar process which give rise to plaques which are focal thickenings of the artery. The worst outcome of this they may rupture and then you get the thrombosis which occludes the artery and that’s the main cause of myocardial infarction or a stroke.
Chris - How do you think we might be able to intervene? Because there are drugs that will lower the cholesterol level, and that’s one approach, but how else might we be able to intervene to reduce the risk of this happening?
Jan - Yes, that’s correct. We have the statins which reduce optimally the risk by 50 percent. We have the remaining 50 percent where we need to find new types of therapies and we think that one could be to get the immune system to help.
Chris- So what, like a vaccine against arterial disease?
Jan - Yes. What happens is that when the cholesterol is oxidised in the artery, it changes structure so the immune system can’t recognise this, so it assumes this is something that comes from a bacteria virus and it attacks it.
Chris - Oh, that’s intriguing. So if you could therefore what: educate the immune system that it’s not harmful when it’s in the oxidised; it wouldn’t be so harmful? Is that the rationale for your approach?
Jan - Exactly. The optimal way for the immune system to react is to recognise this as damage self substances, and try to clear it away and we can try to educate the immune system to do just that.
Chris - How?
Jan - You take a piece of the bad cholesterol molecule, which is called “LDL” and with adjuvants that directly stimulate the generation of these protective immune cells, then you can get the immune system to act protectively.
Chris - Right. So by introducing the immune system to what the oxidised bad form of the cholesterol looks like, with something to make the immune system get excited, that’s the adjuvant, you should get what: an antibody, or immune cells, or both in response to that?
Jan - Yes, there are two types of protective responses that you can activate: one is the antibodies which can then just help to clear away these oxidised LDL. The other one is to activate a form of immune cells which are suppressive, so the go in and act anti-inflammatory and by that way they can stabilise the vascular wall.
Chris - So this is like a two-pronged approach then? On the one hand you’ve got the immune system being able to remove the bad cholesterol and, on the other hand, you’ve got the immune system saying: now don’t get too excited by this cholesterol, it won’t harm you?
Jan - Yes. That’s a very good way to describe it. Actually, rather than making the immune system making thing worse, you can get the immune system to help.
Chris - If one considers a different approach though, which is for Alzheimer’s disease one pharmaceutical company had a vaccine which made a person’s immune system go into the brain and find the protein that was building up that was causing Alzheimer’s disease. The idea being it would remove that protein. The trial for that had to be stopped because the brain became inflamed when they did that. Is there not a danger that with what you’re doing, if you’re programming the person’s immune system to recognise the bad cholesterol, if they’ve got arteries full of it throughout their body could they not get worse inflammation?
Jan - Yes. We learned a lot from that study. And the mistake they did was to choose an adjuvant that made the immune cells very aggressive and that ended up that the immune cells did more harm than protection. So we learned a lot there so we can now choose adjuvants to get milder responses for the immune systems; for example focussing on generating antibodies rather than an aggressive immune cells.
Chris - What stage are you at; are you actually doing this now? Do you have a vaccine that can do what you’re suggesting you’d like to achieve?
Jan - We have a vaccine which we can show works well in experimental models. We’re now developing so it’s safe to give to humans. Then we hope to be able to do a first clinical trial in a couple of years.
Chris - When you say an experimental model, what are these; mice or something?
Jan - Yes, these are mostly mice that we use as experimental models for atherosclerosis.
Chris - So what did you actually do with the mice, and how were they affected by the vaccine?
Jan - We gave the mice a high cholesterol diet.
Chris - What’s that like rodent junk food?
Jan - Sort of!
Chris - And what happens when you do this?
Jan - In the mice we can see that the formation of the astherosclerotic plaques is reduced by about 50 percent.
Chris - That’s a lot!
Jan - That’s a lot. And we are quite optimistic that that could be something that makes a difference clinically.
Chris - But if you can get such a dramatic difference, why is this not already in clinical trials? Why has a pharmaceutical company not chewing your arm off for access to the technology, or are they?
Jan - Unfortunately, not at the moment. There are safety concerns that we have to take seriously. Nobody has used this type of therapy before so there is obviously a risk that we could induce some sort of adverse immune response which we can’t stop, so we have to be sure that we’re doing the right thing. The safety tests that we need to do before needs to be done carefully, and they take time.