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If we had some universal coronavirus vaccine at the beginning of the pandemic, that could have been a great thing for everyone to get, even if it maybe didn't offer as great protection as the very specific vaccines that we got later. That could save, you know, millions of lives uh before we get the very specific vaccine that keep everyone, you know, open, but it wouldn't have had to shut down, but something Keep everyone sane. Why don't we start with the basics? Just tell me what happens when a person encounters a pathogen. What happens inside the body? So, there are two major parts to the immune system. The first is what is often called the innate immune system. If a pathogen or a germ of any kind enters your body, the body will detect this, and it will
send these fast-acting cells that can basically swallow up the pathogens. So, this is kind of like the body's sort of first defense, kind of the initial alarm. And if the um invasion is too big, then this system can also send a um send like a signal to basically get reinforcements in. And these reinforcements are often part of what is called the adaptive immune system. It relies on these types of cells called B and T cells, which have these specialized receptors on them where they can detect very specific pathogens. The B cells produce antibodies, the T cells can basically kill the germs that invade. This system is quite slow, so these B and T cells very specific, but it takes the body a while to find the
specific match for a given antigen. So, it can take a couple of days to mount a proper response, which is why sometimes, you know, if you're if you um encounter a new virus that you'll become unwell because it really takes the body quite a long time to make this sophisticated response. But once you've been exposed to a virus or bacteria, generally what happens is these um B and T cell B and T cells that were used to fight it will be um saved, let's say, as memory cells. So, that if you encounter it again, the body can manage this response much faster. So, where do vaccines fit into this? How do vaccines sort of deploy these different parts of the immune system that you're talking
about? So, the whole idea with vaccines is you want to present the body with some kind of um antigen to a specific virus, but you want it to be harmless. So, you want the body to see the antigen, prepare the response, um so that then you can you will be prepared for the next time when you see the real thing. This is just a protein that's rem- reminiscent of a particular virus, so a way for the immune system to recognize the invader, essentially. Yeah. Yeah, exactly. You said right at the beginning that there's another part of the immune system, the innate immune system, which is this more sort of my words here, primal version. There's just something comes into the body, then
the innate immune system just gobbles it up in some way. Is that something that could be um used to attack or defend against more types of viruses and bacteria than it does at the moment? Yeah, definitely. So, for a really long time researchers thought that the innate immune system was just this very basic, you know, these cells just basically eating the pathogens as they came in. But, actually recently, over the past 15 or so years, that idea has kind of been overturned, and researchers are beginning to realize that actually the innate immune system can be trained.
Some of this research came from a kind of interesting uh source, which is the BCG vaccination, which has been around for century a century. This is the vaccine against tuberculosis, which most of our listeners probably would have had it point in their childhood. Yeah, yeah. People get it in childhood, probably don't really think about it. But Mihai Netea, who is a scientist at Radboud University in Nijmegen in the Netherlands, what he found was that actually the BCG vaccine was really changing the innate immune system to make it better at protecting against a host of other different diseases. And interestingly, you know, there's other vaccines that seem to have this effect
as well. It's not just BCG. Uh there's the vaccine uh the Shingrix vaccine, which protects against shingles. Measles vaccines also seem to have this effect. Polio as well. Um and now researchers are beginning to realize actually maybe the innate immune system is doing a lot more than we first thought and could be a really interesting avenue for trying to generate more broad immunity. So if it's the innate immune system that's being trained or changed to protect against lots of different viruses, how could scientists how are scientists starting to use that information to build um more effective vaccines in the future? What they found is that for
example the BCG vaccine does a couple of different things to the innate immune system. So one is that it causes these so-called epigenetic changes to the genome of these um cells. What that basically means is it is influencing how genes are um turned on or off. And these are the immune system immune system cells, so these macrophages and things for example, which are going around eating stuff up. Yeah, exactly. So the myeloid cells, that's the whole class of these innate immune cells. Um it is Mihai used this analogy of the sort of bookmarking um parts of the genome. And what this does in effect is to keep these cells
activated for longer than they might otherwise have been. And then they're on kind of high alert and they can tackle future infections better. more, basically, and then ready for anything that comes in. Yeah, exactly. Exactly. The other thing that they do is they actually there's a lot of communication between the adaptive and the innate immune system. And so, um some of these vaccines seem to be influencing that communication. And that seems really important, as well. So, have any scientists started to use this uh knowledge to try and design a more broad-spectrum vaccine based around the innate rather than the adaptive immune system? Yeah, so there has been a very interesting new study by researchers at Stanford
that is basically trying to recreate what is going on in the immune system after the BCG vaccine, but using a sort of different system that's a little bit more kind of specific and targeted. The idea of this is you basically want to have this very specific immune response to a certain area, so in this case the lungs, but using these innate immune cells and trying to basically just keep them hypervigilant so that they can fend off viruses, bacteria, and even crazily enough allergens, they found in this study. So, one vaccine could do all of those things? Yeah, so that is what they found. But, caveat, it was in mice.
There are a lot of reasons that might not work out. So, um I mean, for one, mice immune systems and human immune systems are very different, but also, um there are other differences. Mice are often raised in sort of pathogen-free environments. They're doing They're They're having these vaccines on, you know, an immune system that's really not been exposed to a lot. These are laboratory mice, of course, so they're not actual mice, probably with all sorts of pathogens. Yeah, not the cute mice. But, humans, you know, we've been exposed to loads of viruses, bacteria. systems are much more diverse and
and probably, you know, a much more difficult to sort of manipulate in that way. Yeah, I mean, we're starting on a sort of much more complicated baseline and also baseline that really differs a lot between people. So, you know, both for genetic reasons, the immune system genetics are really, really diverse across people. is there, right? The principle that you could try it. We're discovering more about the immune system than we have before and mostly realizing we don't know anything about the immune system. I mean, forgive me any immunologist listening out there because it's a complicated thing. Um but there's lots of avenues for these broad-spectrum vaccines.
Tell me what the vision is then. If this research works out, does that just mean we have, you know, one or maybe two vaccines that can just protect us against everything? I mean, that would be great, but probably not. All the scientists that I spoke to said that they envisaged these broad-spectrum vaccines being given alongside more specific vaccines for, you know, one strain of flu or a very specific coronavirus. They think that these vaccines, the broader the coverage, it may mean that it's less deep, less sort of protective against individual variants. It's also not clear um how long the coverage might last for. But it might be one of these things
where in the run-up to a flu season that we know is going to be particularly bad, everyone gets the universal vaccine as well as a specific version of a specific vaccine for specific strains. And I mean, if you imagine the COVID-19 pandemic, if we had some universal coronavirus vaccine at the beginning of the pandemic, that could have been a great thing for everyone to get, even if it maybe didn't offer as great protection as the very specific vaccines that we got later. That could save, you know, millions of lives uh before we get the very specific vaccine and keep everyone, you know, open, but they wouldn't have had to lock down or something. Keep everyone sane. Daisy, that's been really exciting and
interesting. Thank you so much for bringing us that story. Thank you. Thanks for having me.
