Shingles vaccine and heart disease, and allergy transpoosion

0:00Hey, everybody. It's Farnoosh Charabi from the So Money Podcast. Today's episode is sponsored by NerdWall. Smart Money Podcast, the show that breaks down financial decisions with a team of trusted journalists. You'll get research-backed insights and clear pros and cons, whether you're planning a big purchase or just want to grow your wealth. They explain the why behind decisions like investing, home buying, and choosing credit cards with clear, research-backed insights. Make your next financial move with confidence. Follow NerdWallet's Smart Money Podcast on your favorite podcast app.

0:35All engine running. Absolute genius. Get this. Welcome. Welcome. This is the show where we bring you science. What that essentially means is... Discovery. Advances. Questions. Research. Technology. Unbelievable. Without further ado, this is The Naked Scientist. Hello, welcome to The Naked Scientist podcast, the programme that brings you the biggest breakthroughs and talks to the major movers and shakers in the worlds of science, technology and medicine. With me, Chris Smith. And coming up, shingles vaccine cuts heart disease risks. new research reveals. But how? Also, analysis of the new space race between the US and China.

1:10Why has Beijing put its current project on ice? And are transpusions the answer to treating food allergies? Scientists show that a faecal transplant can prevent peanut reactions.

1:31a new study suggests that as well as cutting dementia risk the current so-called recombinant shingles vaccine also reduces the risk of major cardiovascular events including coronary heart disease heart failure and stroke and by a considerable margin enough in fact to prevent millions of heart attacks and strokes worldwide. Shingles is caused by the chickenpox virus, which remains latent in the nervous system after initial infection and then from time to time afterwards reactivates to produce a painful infectious rash. This happens more often as we get older and as the immune system becomes less agile, hence the push to vaccinate people over the age of about 65.

2:12So an additional health impact on heart disease from doing so could be a considerable win. Oxford University's Fabiana Corsizueli is the lead author on the paper which compared the rate of vascular events among over 70 ,000 US adults who received either the older live form of the vaccine or the newer non-live recombinant vaccine. In this study we were particularly interested in the relationship between shingles and cardiovascular disease. Shingles is caused by the same virus that causes chickenpox. So it's essentially the chickenpox virus coming back and chickenpox almost all of us had as a children, but the virus never really lived.

2:55So it gets quiet, but then in later life, it can become reactivated and causes what we call shingles or zoster, which is a rash that is extremely painful. And the exciting thing is that there are, vaccines against shingles. There are two vaccines. So the old vaccine was what we call a live vaccine. So it contains a weakened version of the virus. And the newer one is actually the recombinant vaccine, which doesn't have the live virus at all, but a protein on the surface of the virus plus an ingredient that we call an adjuvant that really stimulates in a very strong way our immune system. now in the past people have asked a similar sort of question to you but they were looking at associations between getting vaccinated against shingles and getting dementia and they found that the vaccine was strongly protective 20 % reduction in dementia risk in the years that they followed people up but this is a virus that lives in the nervous system hence I can see the link to dementia but why were you interested in the cardiovascular system what's the evidence that shingles has an impact on heart disease?

4:07That's an excellent question. Well, to start with, we know that cardiovascular disease is the leading cause of death globally. And it also has, let's say, a mechanism that is related to inflammation. And the shingles vaccine, the motivation was that the recombinant vaccine specifically could, let's say, reduce this inflammatory response and therefore protect from the cardiovascular outcomes such as ischemic heart disease, heart failure and potentially ischemic stroke as well. How did you test this then? What did you actually do to see if that is the case? So what we did was that instead of comparing people who were vaccinated against people who were not vaccinated, we leveraged the transition that happened in the US, the transition that happened from the live vaccine to the recombinant vaccine.

5:02So let's say that when you compare a vaccinated cohort with unvaccinated cohort, you have something that we call a healthy vaccinate bias. And this is problematic because people who choose to get vaccinated tend to be healthier. So it's difficult to disentangle what's the difference, what's the effect of the vaccine and what's the effect of other confounding factors. And here we have two cohorts, a cohort of people who were vaccinated with the live vaccine before the transition and another cohort of people who were vaccinated with the recombinant vaccine. And with that creates what we say an experimental design to mitigate these healthy vaccine bias.

5:44And what was the outcome measure you were looking for? You're comparing the group of people who had the old fashioned live vaccine versus the people who now get the recombinant not live vaccine. But what are you specifically looking for in terms of the difference between them? So our interest was to look at three major cardiovascular outcomes. So ischemic heart disease, or known as a heart attack. This is when the blood supply to the heart is reduced because, you know, the coronary arteries are narrowed or blocked. We also were interested in heart failure. This is when the heart cannot pump blood as effectively as it should.

6:21And we also looked at ischemic stroke when the blood supply to part of the brain is blocked. And what did you find? So we looked at 70 ,000 people aged 60 and above using electronic health records from the US. And what we found was that people who received the new vaccine, the recombinant vaccine, they were about 9 % free of cardiovascular disease for these three major cardiovascular diseases, ischemic heart disease, heart failure, and also ischemic stroke, ischemic stroke, particularly in men, over the seven years compared to those who received the older live attenuated vaccine. That's a considerable difference.

7:03Yeah, it's very exciting because if we consider that, you know, it's still an observation of study, of course, we need to emphasize that, but it opens like opportunities for now. We test that the cause and effect in proper randomized trials and if the effect holds then that would mean we could prevent millions of cardiovascular diseases and hundreds of thousands of deaths. Fabiana Corsi-Zuelli there on the study she has just published in Nature Medicine showing the new shingles vaccine was associated with a nearly 10 % drop in cardiovascular events in the seven years after it was administered.

7:41But what's the possible mechanism behind this association? Why should blocking shingles which after all lives in the nervous system and temporarily causes a painful skin rash, be linked to heart disease risk. Judy Brewer wasn't involved in the new study, but she is Professor of Virology at University College London and an international expert on this virus. The chickenpox virus, varicella zoster virus and also causes shingles, is able to cause inflammation in vessels, in blood vessels. And of course, blood vessels supply all the body, including the brain and the heart. And it's possible that when you have shingles or you have sometimes cases of chickenpox are associated with little pockets of viral induced inflammation in those blood vessels.

8:34But what the vaccine might be doing is preventing that. So that's one possibility is a direct effect of the vaccine preventing the action of the virus. you have the vaccine and then your virus reactivates which is what shingles is it stops being dormant and it becomes active again then it prevents you getting little micro inflammation in your blood vessels. But if that's the case though Judy what they've done here is to compare the old vaccine the one that was the live but weakened form of chicken pox with the new form which is just a bit of the coat of the virus and they're saying there's a difference So if they're both translating into a reduction in shingles, which means it should be suppressing the action of the virus.

9:19So why would there be a difference if that were true? Well, the new vaccine is much more powerful at suppressing shingles. And it doesn't only suppress shingles, it probably suppresses little micro reactivations that go on that we don't even know about. The old vaccine was a very good vaccine, but it wasn't as efficient as suppressing the virus reactivating. activating. So it's possible that the difference we're seeing is because there's much more suppression of the virus with the new vaccine. That is one possibility. What might be the other mechanisms at play, do you think? Well, if you look at the way that the protection lasts, the protection is greatest from the new vaccine in the first 3.5 years.

10:03And that sort of diminishes a bit over time. And what you would expect if it was protection against the virus, you'd see it actually increasing over time, because basically more and more cases of shingles will occur in the less good vaccine arm, the Zostavax, and the difference between the two vaccines would become more and more exaggerated. And so you probably see less and less cardiovascular disease over time. That's not what's happening here. So another tempting explanation is that it's actually what we call the adjuvant, which is the molecule that's used to jigger up your immune system when you get the vaccine in order to make your immune system respond and make a good immune response against the chickenpox vaccine.

10:51And that adjuvant is known to be a very powerful stimulus. And it could be that that is having an effect and that that effect wears off a bit the further you are away from the vaccine. Do you think the same mechanism would account for the other observation, which is that there seems to be an effect on dementia? We've covered here on this programme before, individuals who receive these vaccines appear to have an up to 20 % reduction in dementia diagnosis in the seven years after they were vaccinated. Quite a powerful difference. Do you think the same thing is going on? Well, yes. Again, who knows?

11:29But yes, it could be that. I'm not sure that you've got the same waning of effect over time with those studies. I can't remember. But I think that the same effect could be going on. I mean, a big caveat here is that none of those studies, none of the studies so far done, are actually good enough. They're pointers, they're interesting, but they're studies that have been done on existing data. And let me give you an example of where this might not be all as simple as you think it might be. For example, we know that the old vaccine contains live virus. It's a very disabled virus, but we know that virus can cause some sort of cardiovascular events.

12:15Chickenpox and shingles do cause inflammation and cardiovascular and cerebral events. and it's possible the vaccine has a slight effect as well. So if you're measuring the new vaccine against the old vaccine, you might be measuring the effect of the fact that the new vaccine doesn't have any jiggering up of inflammation in the arteries compared to the vaccine, which does have a bit. And if you look at the original studies of the Zoster vaccine, there was a very slight increase in cardiovascular events in the first few days following the vaccine, not enough to be a signal of anything, but it's a live vaccine.

12:53So, you know, comparing the new vaccine and the old vaccine is, you know, it's a good control, it's a good comparison, but it's not perfect, as are the studies on dementia, where they've compared, again, they've done the old, the new vaccine gets the old vaccine, and they've also done the new vaccine against no vaccine. And all of those studies are, what we say, confounded. They may be biased by the fact it's being done with the eye of retrospect it's looking backwards and saying ah let's have a look at this we need to have proper forward-looking prospective studies where we control for everything right at the outset and then we measure what happens over time because all of these studies are very nice indicators that we should be looking more carefully but they aren't conclusive what shape should they take then in order to make sure we don't have bias like that because we don't want people to get shingles who are older because that's not nice either but we can't therefore not give them a vaccine so we have to do something how do we solve this it's difficult i mean it's this is something that's very difficult i mean there are people not getting the vaccine you know some countries are not using the vaccine so i mean i don't know whether this could be something that one compares different countries or different control i mean obviously that has its own problems.

14:16I don't know the answer to that, but certainly we need to have much better studies that look prospectively rather than analyse data that is already existing before I think we can be really sure. But you're quite right, we can't really, nowadays, it would be very difficult because we can't actually not give the vaccine to people. So yeah, that is difficult. So go grab your shingles jab. Judy Brewer at UCL. Thanks, Judy.

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15:42This is the Naked Scientist podcast with me, Chris Smith. Still to come, the frozen poo pills that can stave off allergies. But first, many of us had assumed that the race back to the moon was a formality and that China's much vaunted Chang 'e 7 space programme would blow away the United States and the perceived prudence of NASA's Artemis missions. Beijing's leadership had pinned their hopes on landing closer to the moon's exact south pole than any other spacecraft had done before. But the mission has now, suddenly, without explanation, been delayed. Rana Mitter is the Chair of US-Asia Relations at the Harvard Kennedy School.

16:19There's a bit of a glitch, a bit of a delay in the Chinese space programme, because their Chang 'e 7 probe mechanism, which was supposed to be sent to the moon's surface to look for water at the south polar cap, has had to be delayed. We're not quite sure of the reason. To be honest, the Chinese don't tend to give us very transparent reasons for delays in any of their programmes, but we think it may be to do with the weather, perhaps here on Earth, not on the moon. The idea, though, is to try and find water. And the reason for that is that as part of the wider competition in space, it's no longer just about visiting the moon.

16:50It's about staying there. And water is, of course, the absolute necessity for whatever nation, whatever country sends travellers to the moon. So the US is definitely in that race as well. The Artemis programme has become quite well known, and they want to send people back to the moon by 2028. The idea of sending probes looking for water that can be exploited, used, maintained to keep a permanent human presence on the moon. That's really at the heart of the current US-China competition. Russia's still involved. It's got a big satellite presence as well. And of course, it's more oriented towards China these days.

17:21But the real key players are the United States and China. Harvard Kennedy School's Rana Mitter explained in the context of the new space race between Washington and Beijing. Well, let's unpack this a bit further now. with Richard Hollingham from the Space Muffins. Well, China has been making slow and purposeful, steady progress towards landing on the moon and ultimately getting humans on the moon. That is the ultimate goal, to have a lunar base. There have been six missions so far. There's been an orbiter, there have been landers, there have been sample return. And so they can see a time, maybe 2030 or the 2030s, where they get humans on the moon and then ultimately establish a base.

18:05This has been going on since the early 2000s. It is very purposeful. There is a plan here, whereas the US has had plans. They've abandoned plans. They've got back into plans. They have a new plan. China, with the way their government is set up, has just been absolutely going for it. So laser focus. We were all expecting them to really give America a run for its money or even get there first. Now that the word is it's all off. It's off at the moment. So Chang 'e 7, I mean, this is a remarkable spacecraft. So this lander, it actually consists of an orbiter, a lander, a rover, and a hopper. So it's got 18 scientific instruments on board, including cameras, infrared, mineral analysing instruments, and then this hopper, so it's a little sort of bouncy rover.

18:55It contains an instrument and a drill to look for water molecules. That's what they're after. So they're most likely, we don't know exactly where they're planning to go, they're most likely going to the Shackleton Crater near the lunar south pole looking for water, for water ice. And I mean that would be amazing that it's on the moon but it would also be incredibly useful if you want to live on the moon to have a source of water. What has changed then? What have they actually said officially has changed? Yeah, it's so difficult to get any proper insight into the Chinese space programme other than what we can see and also what they tell us.

19:37They tell us very little. So this launch was abruptly called off. We don't know exactly why. It could be to do with the rocket. They say it failed to meet launch criteria. Well, that could be any number of things. So that could be the lander. That could be the rocket. that could be something as simple as the weather not being right. So we don't know. I mean, this is a problem with the whole Chinese space program is the way they control information. And I think sometimes it comes back to bite them because they'll talk up these missions and then suddenly it's cancelled. And then you end up with the whole rumour mill of, well, why was it cancelled?

20:13What's going on? Is there some secret behind it? It could just be that the rocket wasn't ready or there was some little glitch. We see that all the time with NASA missions. But of course, NASA is open, honest, and you see and there's an inquiry or they say, well, this bit doesn't work and we'll do it again in a few months time. So you just don't know with the Chinese space program. Has NASA said anything? Not really. They tend not to comment on these things. They tend to have not have a relationship with China in space. And this is such a pity, really, because, I mean, right now there are actually three, there are three Chinese astronauts in orbit, but there are also astronauts in orbit on the International Space Station.

20:55They do not communicate with each other. There's no contact, official contact between the programs. I mean, this is quite tied up in in US sort of technology law. So, you know, none of this high tech technology that NASA develops. The idea is none of that ends up in China. So as a result, there's a real suppression of kind of information or any sharing with the Chinese. And that works both ways, of course. But you could end up, we could potentially end up, as we are at the moment, with these two space stations in orbit, two nations just not cooperating in space. We could end up with the same situation on the moon, where you have the Shackleton crater near the South Pole.

21:37And you essentially have a base on either side of it. you know you could have a chinese base an american base and they do not talk to each other that is the situation we've got at the moment that it seems extraordinary when you've got you know nasa talking about for all mankind well it's for all mankind apart from china and china's just doing its own thing where does this leave the sort of pr side of it though because the chinese also die now on doing these things very well and succeeding look at the the robot olympics that we've had and people are saying hasn't that really got people talking i mean we're talking about it now does this mean china are going to take this as a bit of a oops because it's giving the americans a bit more of an opening well that's my point really if you try to overly control the message when things go wrong it just leaves a vacuum and you end up with this kind of rumor mill which is what we've got at the moment and everyone's sort of second guessing what's actually going on if they were more open and honest, people get that space is really difficult.

22:38You know, you can't just say, right, we're going to launch to the moon and do this, this and this. You know, even the best laid plans, as we have seen, can go wrong. And as we see all the time with NASA missions or US missions. But you learn from those. I don't really see the argument for being so secretive when it comes to this sort of space program. and certainly the lunar programme. I just don't see the reason for that. I mean, maybe we will see some changes, but as we know, China absolutely controls all information and very much keeps a lid on what's going on in the space programme. Richard Hollingham from the Space Muffins, and you can hear more from them on All Things Space Science via our Naked Astronomy podcast feed.

23:24You get that at nakedscientist.com forward slash astronomy or look up Naked Astronomy wherever you get your podcasts. Meanwhile, back here on Earth, at Boston Children's Hospital in fact, scientists have found that a transpusion, a faecal transplant, might hold the key to combating severe food allergies to things like peanuts. After eating a handful of frozen food pills, crapsules colloquially, prepared from non-allergic individuals, previously food-reactive volunteers could tolerate significant exposure to peanuts that would previously have caused some problems. Reema Rashid has the story. In an earlier study in 2019, we published in Nature Medicine that there was significant difference in the bacteria that live in our gut between the babies who were healthy and babies that had food allergies.

24:15When we took the stools of the babies that were healthy and we put them into a highly allergic mouse model, it completely protected from anaphylaxis, which is a severe allergic reaction. That was not the case when we used the poop of babies that were food allergic. So what that's pointing towards is that the microbiome, the assemblage of microbes living in us and on us, is in some way manipulating the way that we react to or interact with potential allergens in the environment. Yes, indeed. The healthy microbiome upregulates particular cells that are important for the protection against food allergy.

24:56If you actually use certain bacteria in the highly allergic mouse model, you can treat food allergy. However, if you delete the capacity to produce these regulatory T cells, there is no protection from anaphylaxis, even if you put the right bacteria. What did you do here then to try to explore further how this is working? So we decided that we're going to now do a trial in humans, where we're going to take fecal material from humans and use encapsulated forms and give them to patients with peanut allergy. We initially had to prove that the patients were allergic, so the patients had to eat a small amount of peanut, and we had to prove that they had a convincing reaction.

25:43And after that, the first 10 patients received 36 encapsulated fecal material, 36 capsules over a three-hour period. And then the patients went home and we repeated the food challenge a month later and four months later. And by food challenge, you're exposing them to peanut to see if you elicit the same reaction. And were they as reactive or had the reactivity changed at that point? So three out of 10 patients had an increase in the dose at which they reacted one to 300 milligram which is about more than a peanut or two peanut and a half one to 600 milligram and one tolerating all doses which is a cumulative of four peanuts.

26:30And you ascribe the improvement to the faecal transplant you think that that is what's driving this different reaction? Yeah and because we saw three out of ten patients improving we're like what would happen if we were to give antibiotics prior to the fecal transplantation. Would that help eliminate some of the patient's microbiome and help the donor's microbiome implant better? So we repeated the trial, and this time we enrolled five patients who received prior to fecal transplantation four days of broad spectrum antibiotics. Then they received the 36 capsules of fecal transplantation, and three out of the five patients who were reacting to 100 milligram peanut protein or less went up to the 600 milligram.

27:19So now we have six out of 15 patients who actually improved. And now back to your question, why do we think it's the microbiome? Well, we took initially the stores of the responders, who are the patients who responded, basically, we call them the responders. And we put them into the highly allergic mouse model and there was no protection from anaphylaxis when we used the stools of the patients at baseline. However, when we took the stools four months after they were transplanted with the healthy microbiome and we put them into the highly allergic mouse model, there was protection from anaphylaxis.

27:57And that experiment was repeated by two different operators and it was consistent. Can you demonstrate though, that you have actually changed the microbiome in the recipient humans? I know that you're saying that by doing this transplant in mice, it certainly looks like you've done something. But can you show by looking at the genomics or whatever, the population level of the microbes, that something has fundamentally shifted after these transpusions? This is an excellent question. This was a small trial, so we didn't find a difference when we looked at their microbiota. And we think that it could be because this was a small trial.

28:35Although there are some studies such as melanoma trials and ulcerative colitis trials where patients responded even though there was really no difference in implantation between those who responded and those who didn't. So it's possible that what we're getting is more like an interaction between the bacteria and the immune system at the level of the intestine and maybe the small intestine. Well that was going to be my question which is is it that it's a transient thing that this new population of microbes comes through does something to refashion or remould the immune response and then they leave the premises but they leave this imprint on the immune system that seems to translate into a better tolerance of whatever the person was intolerant of before.