Non-specific Vaccine Effects

Both beneficial and harmful ones

Thanks to one of my readers, Laura, who sent me this video. It is one by Sebastian Rushworth MD (SR), interviewing Christine Stabell Benn (CSB) on the really interesting topic of non-specific vaccine effects.

“Christine is a Danish physician and a professor at the University of Southern Denmark. For almost 30 years, Christine has been a vaccine researcher and she’s being doing research, mostly in West Africa, a country with a high death rate from infectious diseases but also doing some research here in the Western world. The focus of her research has been on non-specific vaccine effects, i.e. all those other effects on our immune system and our health that vaccines have beyond their immediate effect, in terms of protecting against one specific infectious disease.

Her findings have actually been pretty amazing and have upended what has previously always been believed about vaccines, that they impact our protection from one disease and that that’s pretty much it. What she’s found is that certain classes of vaccines have an effect on overall mortality, that can’t be explained by their impact on this one disease they’re supposed to protect against, so they’re clearly doing something more, providing some additional benefit and she’s also found that other classes of vaccines have the opposite effect so that even thought they’re protecting against one infectious disease, overall they’re actually increasing mortality, so there is some kind of harm that they’re causing.

This is an in-depth conversation where we go into detail about vaccines and their both beneficial and harmful non-specific effects. We also touch on the Covid vaccines and get Christine’s opinion on them.”

The video is below. For those of you who cannot watch the video, would prefer to read in more detail, just skip read or skip to specific questions, I have transcribed it below (for paid readers only).

The transcription below is for paid subscribers only. My articles take a lot of time to research and write so your support is very much appreciated and will ensure that I can continue to produce the same quality of articles going forwards.

SR - The focus of your research is non-specific vaccine effects, could you explain a bit about what a non-specific vaccine effect is and how this came to be the focus of your research.

CSB - Non-specific effects of vaccines are the effect of vaccines on the immune system, the more general effects on the immune system that may affect how the immune system responds to subsequent challenges, also those unrelated to the vaccine disease.

I came into this research agenda in ‘93, so almost 30 years ago, but at that time it was already established by my mentor, Peter Aaby, who is actually an anthropologist, but started working in Guinea-Bissau in 1978 and very quickly realised that measles at that time was a big killer of children and as a service to the community they gave measles vaccines to all children who were at home when they were doing their rounds.

At that time there was no measles vaccine available so this was really an additional vaccine that the children wouldn’t have had otherwise and what turned out to be a major observation was the fact that when they came back a year later there was a huge difference in mortality among those who had received and not received the measles vaccine. Everybody knew what measles was and could diagnose it and it was very clear that the children who had died, had not died from measles, they died from other causes and the huge difference in mortality, an almost 70 percent reduced mortality, in those who had received the measles vaccine could not be ascribed to just prevention of measles infection.

So this was a major observation that really contradicted everything everybody thought they knew about the measles vaccine because it was only supposed to save the children who would otherwise have died from measles but it turned out that it seemed to save children from a lot of other infections that were prevalent at that time.

That was so incredible, so of course that was not an observation that in itself could lead to a change in the understanding of vaccines but what Peter did, after realising this dramatic effect of measles vaccine, was to approach other sites around the world, who had introduced measles vaccines and had data on the overall mortality effect, and it turned out that in all the available datasets, the introduction of measles vaccine was associated with at least a 50 percent reduction in all-cause mortality, so dramatically more than could in any way be anticipated from just protecting against measles.

This was Peter’s observation and might have been dismissed if it was a medical doctor because the medical doctor would have been primed to think that this was impossible. How could a vaccine against measles protect against other diseases but I guess for an anthropologist, with an unbiased mind, it was just the data that spoke and the data spoke a very clear language.

I’ve formed a team with Peter ever since, where we have managed to cover a total of ten vaccines with this type of evaluation and discovering for all these vaccines, that we have studied, it turns out that their overall mortality effect cannot at all be explained by their effect against the vaccine disease.

SR - All this data is observational or do you have trial data supporting this too?

CSB - Clearly this is observational data. We know there is inherent bias in studies of vaccines and that is that generally it will be the healthy children who are vaccinated first, so there is a bias in favour of any vaccine that you study when it’s just about comparing those children whose parents brought them for vaccination with those children who weren’t brought for vaccination because everywhere in the world, parents are reluctant to bring their ill children for vaccination. Clearly any observational studies showing some mortality difference between vaccinated and unvaccinated children could be suspected to suffer from what we call “healthy vaccinee bias”.

So it has been extremely important that we have been able to take many of these observations forward to randomised trials and generally speaking, just as a rule of thumb, if we see a 50 percent mortality reduction in an observational study, that translates into a 30 percent mortality reduction in a randomised trial, so that gives you an idea about the size of confounding or selection bias that’s introduced in the observational studies but what remains is that even in randomised trials, we see these strong effects on mortality which cannot be ascribed to the prevention of the vaccine disease and the interesting/worrying thing is that for some vaccines we actually see that in the observational studies, when we compare those vaccinated with those unvaccinated, there’s a higher mortality in those who have been vaccinated.

So I started out talking about these strongly beneficial effects of measles vaccines but the problematic observation and the real controversy here is that we actually also see that for some vaccines it’s opposite, the vaccines protect against the vaccine disease but, in spite of that, their introduction is not associated with lower overall mortality and if we compare kids who have received the vaccine versus those who haven’t received them, in spite of all these biases, those who have received the vaccine are still dying more than those who haven’t received the vaccine. So, the benefits of being protected against the vaccine disease seem to be out-balanced by a negative effect of the vaccine and the risk of other infections.

SR - So you see both this positive non-specific effect with some vaccines that they have this extra benefit, in terms of reduced overall mortality, that can’t be explained just by their disease specific effect and then you have other vaccines, where it’s the opposite, where you actually see increased mortality even though you would expect a decreased mortality because they have this disease specific benefit.

CSB - Because they have the disease specific benefit and because also the observational studies would be prone to this healthy vaccinee bias. So you can see, even though all the biases that are available, both the effect of the vaccine and the biases would work in favour of the vaccine but we see this opposite pattern.

SR - What do you think explains these non-specific effects and why is there this difference with some vaccines showing a beneficial effect and some showing a harmful effect?

CSB - The pattern we have observed is that the live vaccines, the live attenuated vaccines, which mimics a natural infection, its just so mild that you really don’t get any symptoms, these vaccines are all associated with beneficial non-specific effects, so larger reduction in all-cause mortality but in contrast the non-live vaccines, where you have the dead disease organism or products or parts of the disease organism, there you see the negative non-specific effects.

Those two types of vaccines are actually quite profoundly different in the way that the immune system handles them because the live vaccines normally create a broad immunity after one dose so you rarely need more than one dose to get good, long protection against the vaccine disease. We know that for the measles vaccine, MMR vaccine, we give two doses but it’s really just to safeguard because more than 90 percent will be protected for life by just one dose.

The non-live vaccines in contrast, you have to get booster shots or have a series of vaccines, like the hexavalent vaccines against diphtheria etc. You need to give them so many times because they are pretty inert and the immune system isn’t very interested. Sensibly enough, it thinks well here’s something dead, it can’t really threaten me, so why should I respond to it. So the non-live vaccines often have to be given with an adjuvant, a helper substance, to make the immune system respond and it has to be given in several doses to really create immunity.

In the end, both types of vaccines will create good immunity against the vaccine diseases but they do it in a quite fundamentally different way and it seems these differences are very meaningful in terms of how they then train the immune system against all other pathogens as well. We are still trying to understand how this takes place because this is clearly contradicting everything in the medical textbooks which say that a vaccine should not be able to induce memory towards other disease organisms.

You have learnt about vaccines, how they will go in and be picked by an antigen presenting cell that will activate B-cells, T-helper cells and T-killer cells and our focus has been on the B-cells which will then turn into plasma cells and produce antibodies, which specifically recognise the disease organism and create B-memory cells, which will stay there with this memory of this particular disease organism. It has been so self-evident to medical doctors that this was what happened and nothing more would happen, that nobody ever cared to look if the vaccines could affect other arms of the immune system and their response to other disease organisms.

SR - I know this is the standard but isn’t it strange that we do studies in such a way that we’re only looking at the disease specific benefit, shouldn’t studies always be looking at the overall effect? Who cares if a drug decreases your risk of one thing if at the same time increasing your risk of something else. Shouldn’t that be the standard in medical research, why do you think it isn’t?

CSB - I’ve read the book Ending Medical Reversal by Vinay Prasad and Adam Cifu, where they deal with exactly that question and propose that we are somehow biased by our own perception of how good we are as medical doctors to understand the physiology, the pathophysiology etc. So we do think that if we give a cancer treatment that makes the tumour shrink, then obviously it must be beneficial for overall mortality, so we don’t really bother to study it.

We do think that if we have a screening programme against prostate cancer that detects the cancer earlier, then of course it must also translate into lower mortality but again, we are so certain, that we don’t bother to study it. In these situations I think it’s more and more generally accepted now that these surrogate outcomes are not associated with the overall health outcome and we may make some very big mistakes if we use the surrogates as outcomes for our clinical trials and as a treatment outcome because we have seen numerous examples and that’s what they expose in their book, of how completely biologically plausible surrogate outcomes turn out, in fact, in real trials and assessment, not to be associated with lower mortality.

On the contrary, for a patient, you don’t care if your tumour shrinks or if it’s detected earlier if it doesn’t affect your final outcome, whether you live or die and potentially the treatment you take will make you feel lousy and the screening programme will turn you into a patient much earlier than you had otherwise been and make your life miserable. I think it’s more generally accepted for cancer treatments for screening and so on but what’s still surprisingly difficult to transmit is the fact that just looking at a vaccine’s effect against the vaccine disease is not associated with the predicted effect on overall mortality either and we might make the same type of mistakes if we only look at the vaccine’s effect on the vaccine’s disease.

SR - You see this kind of clear difference between live vaccines and non-live vaccines and is that like a general class difference that regardless which live vaccine you look at you see this beneficial effect on overall mortality and regardless which non-live vaccine you look at you see a neutral or negative effect on overall mortality. Is that the case across the board?

CSB - I'm reluctant to say that it's a general pattern because there might still be things that contradict this pattern but it is the pattern we have observed and I'm quite astonished by it because we are talking about quite heterogeneous classes of vaccines. So within the group of live vaccines they are not at all very similar, the thing they have in common is being live, they replicate, they divide themselves in the body and and other people have shown that there are receptors in the body that sends this kind of important signal for the body that here you have a disease organism that can actually replicate, so we know it turns on a different kind of signalling than the non-live vaccines.

The measles vaccine is injected subcutaneously, the oral polio vaccine is given as as drops on a sugar lump, so they come in via the mucosa, so they're quite different. And particularly with regards to the non-live vaccines they are also very heterogeneous, so when we have been looking for commonalities. In the beginning the non-live vaccines we studied were aluminium actuated so we thought maybe it's the alum that's the culprit. It has a tendency to trigger the immune system into what we call a TH2 direction and it's used historically because it just gave good antibodies, it's really turning on the arm of the immune system, where you can get antibodies so we thought maybe the alum will twist the immune system away from the TH1 response that it needs sometimes and then really misdirect it in a TH direction. But then we studied other non-line vaccines which weren't alum activated and we saw the same negative effects, so alum is not the commonality.

The common thing for the non-live vaccines is that you give them into the muscle which is, technically speaking, also a quite stupid place, because the immune system is not present in the muscle, it's not where you’re supposed to meet your pathogens, they come in by your mucosa, so you don't have a standing arm of immune cells in your muscles but that's where you inject the non-live vaccines and that's where all the immune cells are heading and that we have speculated, could somehow lead to a different compartmentalisation of your immune cells, it might actually be part of the explanation why it could misdirect the immune system.

SR - How long do the non-specific effects last, is it months or weeks or years or how how long say after the BCG vaccine do you see this benefit on overall mortality?

CSB - BCG and smallpox vaccines are the vaccines where we've seen effects persist for decades. We did a study in Denmark where we looked at the cohort born between ‘65 and ‘76 so this was the cohort that experienced both these vaccines. They went from almost 100 percent coverage to almost zero percent coverage over this 10-year period so this was what you call a natural experiment, this is a situation where there wasn't much healthy vaccinee bias, it was really the year that you were born that determined whether you were vaccinated or not and we followed all these cohort members up to the age of 45 and we could show that there was more than 40 percent reduced all-cause mortality, from natural causes, if you had been BCG or smallpox vaccinated versus if you hadn't received any of these vaccines.

So, reassuringly, there was no effect on murders and suicides and accidents but if we looked at all the natural causes, we saw very broadly that mortality was significantly reduced in those who received those two vaccines. One thing that's important to mention, is that these non-specific effects are strongest as long as a vaccine is the most recently given. In low-income countries, after BCG vaccine, if we compare in the time window where BCG is the most recent vaccine, we can see that those who received the BCG vaccine have lower mortality than those who didn't get the BCG vaccine. Then at the age of six weeks all the children are offered a DTP vaccine, then in this time window, comparing those who received the DTP versus those who didn't, those who are vaccinated have higher mortality compared with those who weren't vaccinated. Then comes the measles vaccine at nine months and then it's vice versa again, those who were vaccinated with the measles vaccine have lower mortality than those who weren't vaccinated with the measles vaccine and it's the same kids we follow over time so these patterns we see indicate that these non-specific effects can be abrogated and this is the good news in terms of the negative non-specific effects of non-live vaccines, that they seem to be gone when you give a live vaccine you can train your immune system back to the state where it's prepared to meet other enemies.

So given the nature of the vaccine programme, where vaccines are given sequentially, we haven't had much opportunity to follow the long-term effects of some of these vaccines but at least I would say they last six months or until a new vaccine is given and for some vaccines we have evidence that they may last for decades and also may last in spite of other vaccines being given afterwards. So with the BCG and smallpox vaccine it seems that there is some long-lived imprinting effect which can override whatever happens afterwards.

For BCG it has been a puzzle, how could a vaccine have such effects on other pathogens but also how could that be sustained over a long period. We have shown now that BCG enters the bone marrow and trains the stem cells so the mothers and fathers of all your innate immune cells that hide in the bone marrow and produce new cells when needed, they change their phenotype, they simply change their profile after meeting BCG and they're the ones that stay in the bone marrow. The immune cells go out and die after a short time but there will continuously be produced more that will have this new memory from having that BCG.

SR - There's been this gradual transition where more and more vaccines are non-live, at least in the western world I think the vast majority of vaccines people are given are non-live vaccines. Do you think overall that is a harmful trend that should be avoided or how should be we be handling that in light of your research findings?

CSB - It's important to say that the majority of our findings are done in Guinea-Bissau, in low and middle income countries and our outcome of interest has been overall mortality. Mortality has been high so we have actually been able to show significant differences in mortality.

In our part of the world, fortunately it's not an outcome that you can use for childhood vaccines because mortality is so low but we have looked at another markers of overall child health, namely the risk of getting infected or getting hospitalised with infectious diseases and we do see some similar patterns in our part of the world. So what we have shown in Denmark is that if you give the measles mumps rubella vaccine, then the risk of getting hospitalised with infectious diseases decreases compared with the children who remain with their DTP vaccine.

We have these issues with healthy vaccinee bias in our part of the world also but at least in Denmark there is some delay in when your child is 15 months old and you have to call the medical doctor to make an appointment for the MMR vaccine, then you can get an appointment three weeks later and so on. So we have adjusted for all kinds of confounders. We do think we see a reliable pattern of lower infectious disease hospitalisations after MMR. Colleagues from the CDC in the US have found a similar pattern with a lower risk of non-targeted infectious hospitalisations after live versus non-live vaccines, so the effects are less pronounced in a setting like in a high income setting where infectious diseases are not that prevalent but they're not that deadly, fortunately but I still think it could make a difference.

It does seem to make a world of a difference in low income countries. There's an Australian paediatrician who made calculations based on the WHO's review of non-specific effects, which took place in 2014 and produced a series of estimates of effects of these different vaccines and just using these effects, estimates from the review and looking at the recommended childhood vaccination program in low-income countries, he calculated that if the vaccination program was altered to optimise, not only the specific but also the non-specific effects of vaccines, using the same vaccines, just in a different order and sequence, could reduce global child mortality by one million deaths every year. There is a huge potential in using live vaccines, using the vaccines intelligently so they optimise also the non-specific effects.

SR - Why don't we just replace all non-live vaccines with the live vaccines?

CSB - I think the major stumbling point is that it’s important to mention that live vaccines carry the tiny risk that if you give them to people who have weakened immune systems they can actually become vicious. So if you have AIDS, not only HIV positive but you have AIDS, you're immunocompromised, then you can get BCGitis, you can actually get an infection from the BCG vaccine against tuberculosis which can, in worst cases, kill you. So clearly the live vaccines are wild beasts that we have leashed and normally they would never hurt you but in a very immunocompromised person, and we're not just talking about somebody who says I get ill all the time, we're talking about people who are severely immunocompromised, in such people the vaccines can cause a real disease or something similar, so that is a caveat with live vaccines.

Plus they are quite difficult to produce and also to handle in the vaccine chain, out from the producer to the children because they typically have to be kept cold. They are often freeze-dried, once you dilute them you have to use the vaccine within four to six hours, so there are also some logistical issues but in many people and many settings, these small problems, so to speak, with the live-vaccines would be easily overcome and again there really seems to be some potential both in terms of the specific protection that we touched upon, that's easily achievable and often with fewer doses and often more long lasting with the live vaccines but particularly in terms of the non-specific effects.

SR - Those negative aspects seem very small in relation to the fact that it's only with the live vaccines that you're actually seeing any benefit on overall mortality and it's hard to see how you can make a positive cost benefit analysis if you're not actually seeing any overall benefit of giving a certain treatment.

CSB - One good example which is something that's keeping us awake at night right now is the oral polio vaccine and the inactivated polio vaccine. So this is a disease which is almost eradicated but where we have a live and an un-live vaccine and the high income countries have more and more switched to the non-live polio vaccine, because the live vaccine can also, in rare cases, give polio-like disease in those who receive it but in the low-income countries it's much cheaper to give the live polio vaccine and it's easy to administer in the mouth and it gives good immunity also against transmission.

It's actually the only way we can ever eradicate polio because the inactivated polio vaccine, like most non-live vaccines, it gives you antibodies in your body so you don't get ill if you get polio but in fact it doesn't prevent you from getting polio in your mucosa and getting infected, it just prevents you from getting diseased but the oral polio vaccine also prevents you from getting infected and from transmitting to others so has been used and is being used in low-income countries to eradicate polio. But it has a small problem, last year it was 17 children globally who got this polio-like disease, so it's a tiny number of children but that is why the WHO is now trying to stop all polio vaccines and the plan was to stop it by 2020, now the plan is by 2024. I don't think they will manage it because there's still polio here and there and they can only eradicate it with the old polio vaccine.

I'm getting grey hairs by the thought that we are about to stop a vaccine which now, in our studies, we just recently started studying it actually, it was kind of number 10 in the line of vaccines we studied but it's associated with tremendous reductions in child mortality, so every time there's been a polio campaign we can show there is a 15 percent reduction in all-cause mortality and we can actually historically show that during the last 20 years when all polio vaccine has been used in campaigns, it can explain most of the child mortality decline that has been seen in low-income countries. So the real fear is that this vaccine, the live vaccine against polio is stopped and we will see child mortality start increasing again because there's nobody who is studying the overall health effect of inactivated oral polio vaccine.

SR - I'm a parent, I have small children at home and I guess probably some of the people listening are parents too, so in light of these non-specific effects, if as a parent you want to optimize your child's overall health, rather than their specific protection for various infections, how should you be thinking, should you just follow the official vaccine recommendations or should you be interfering in some way, saying yes to certain vaccines, no to other vaccines? How should I be thinking as a parent in terms of which vaccines I let my children take?

CSB - I usually say when I'm presenting, I have a disclaimer right in the beginning because I'm saying things that could easily make people project me as an anti-vaxxer and it should be hopefully obviously for anybody seeing this that I'm not an anti-vaxxer but you know people are adjusted to the public messaging about vaccines, their hashtag vaccines work, they're safe efficient don't worry etc. So anybody raising issues like the ones I'm raising here is having to walk on a very narrow line and make sure that the messaging is as balanced as possible and I always start by saying that I have two children myself, a girl and a boy.

One thing we haven't talked about is that these non-specific effects are sex differential, so the negative effects are primarily seen for the girls and only, in some instances, seen for the girls, which is yet another intriguing thing that we are trying to understand better but in both cases, with my son and my daughter, they followed the the common childhood vaccination programme in Denmark and it's actually a pretty good vaccination programme because even from a non-specific point of view it makes sure that children in Denmark have live vaccines as their most recent vaccine for the majority.

I would go on a very dangerous path if I started giving specific recommendations and alterations to the programme but I do see potential for improving it, for instance in Denmark we give the MMR booster at four years and we give a DTP booster at five years, an un-live booster at five years and there's really no good reason why it should be in that sequence.

So I would much prefer, from a non-specific point of view, data would indicate, it would be better to give the MMR vaccine at five years and and the DTP booster at four years but if I were the minister of health or the head of the Danish medical board I would love to do a large-scale randomised trial that the Finnish are famous for doing making one region do one programme, another region do another programme. You could do cluster randomized trials, where you could do different schedules which should have no overall impact on specific immunity but could have potential impact on non-specific immunity, where you could compare them against each other in an unbiased fashion and really look for ways to optimize our vaccination program while making sure that children get their vaccines.

SR - We already talked about how we already have the Covid pandemic ongoing and we've had these massive vaccination campaigns and all the vaccines currently available are non-live vaccines which I guess you would then assume don't result in any reduction in overall mortality and might even increase it. So this might be the part of the conversation that we need to cut out if we want this video not to be removed from YouTube but I was just wondering how you feel personally about the Covid vaccines in light of this?

CSB - I have said that openly so I'm happy to say that on this podcast also. It's clear from the discovery of non-specific effects that the current system for testing vaccines is not sufficient because it only looks at the effect of the vaccine against the vaccine disease and then it looks for plausible side effects and they are typically registered within the trials leading to approval of the vaccine. They are registered within the first weeks after vaccination in the typical forms that we know, fever, headache, fatigue etc.

Then the trials also capture serious adverse events leading to hospitalisations and death and that may go on for longer or that does go on for the full duration of the trial but most of these serious adverse events that occur are dismissed as not being related to the vaccine because nobody, as a starting point, anticipate that the vaccine would give anything but these typical side effects in the first weeks.

So one example is appendicitis which came out as a signal in, I think the Pfizer trial, that led to approval of the vaccine but where those assessing the serious adverse events and saw there were more appendicitis in the Pfizer vaccine, said this is probably not related to the vaccine because why should the vaccine give appendicitis but that signal was later confirmed when the vaccine was rolled out in Israel. There was a 40 percent significant increased risk of appendicitis in those who got the Pfizer vaccine versus those that hadn't gotten it yet.

So coming back to this thing we started with, with the biological plausibility, as long as nobody has studied a new vaccine, everything is basically plausible in my point of view but it looks as if, for the people conducting the trials, if you look at the list of severe adverse events and the way they're judged in the trials, their default is more the other way around, that unless something is very biologically plausible somehow, and I guess basically the presumption is that nothing is biologically possible, the burden of evidence is towards proving over any doubt that the new disease occurring after vaccination, the serious adverse events was due to the vaccine rather than the other way around.

The real problem from my point of view is that any infection occurring after vaccination in a randomised trial, a clinical trial for for approval, would be dismissed the way the system is right now. With the current paradigm for vaccines nobody would see a pneumonia with a bacteria occurring three months after your mRNA vaccine as a potential result of the vaccine. It would be dismissed before you could even write it on paper as being due to the vaccine but for all we know it could very well be the result of the vaccine twisting your immune system so that you became more susceptible to other disease organisms.

That's a flaw in the current system for testing vaccines that they don't look for non-specific effects, they don't look for other infections and if they see them disproportionately, then they would be dismissed as a chance finding because it would be said it was biologically implausible.

For the mRNA vaccines and the adenovirus vector vaccines, I've actually been in doubt whether they were live or non-live. I'm not happy with the way they were tested because they didn't test for overall mortality and morbidity and they didn't look for very long, whereas we know the non-specific effects could last at least six months and potentially longer, so the system was not good enough.

I've been in doubt whether the Covid vaccines would be live or non-live because they're really a new type of vaccine and it could be that the way the mRNA is processed in the cell, particularly with the adenovirus vector vaccine, that it could resemble something that was a live pathogen but the only study we have so far is from our Dutch colleagues who looked at the Pfizer vaccine and saw that it had a pattern that looks like what we've seen for non-live vaccines. So it induced, two weeks after the second dose, those who had received them, had a more lazy innate immune system. They had increased tolerance, so if you stimulated their cells with other viruses and bacteria they didn't respond as much as before the vaccine.

So this is a tiny piece of evidence and I want to emphasise, I don't want to say that in any way it should scare people away and think this vaccine has negative non-specific effects but the tiny piece of evidence we have point in that direction.

Plus I should say I'm not completely happy with the overall mortality in the randomised trials. Clearly the trials didn't look for it, the trials were not sized to look at overall mortality but if you just look at the crude mortality there were no reduction in overall mortality. There were not less deaths, there were actually a bit more deaths in the vaccinated in the control trials than in the unvaccinated, in spite of the fact that there were fewer Covid deaths.

So very tiny pieces of evidence, which, to me, suggest that it would be extremely important to study these effects for these vaccines for their effect on overall mortality. The jury is still out.

SR - The thing I find most shocking about the Covid vaccine trials is that two months into the trial they gave the vaccine to the control group, so we don't have any long-term follow-up and like you say non-specific effects can be expected for months or years out and we'll never have that data now because there is no placebo group from more than two months out in the trials.

CSB - Well four months I think, at best, but it's too short a time and I completely agree with you and I find it appalling that the control group was vaccinated. After all they had entered the trial on the condition that they were going to be in the control group for two years. I think we could have maintained that randomisation for the sake of mankind.

We need this kind of data and particularly now when we're rolling the vaccines out to so many millions of people and this is why I've been strongly advocating that we should not vaccinate people who weren't at risk of Covid. So with the disease that has such an age mortality profile, clearly if you're over 75 and have other morbidities etc, it looks like a very good idea to get the vaccine and you could live with a quite substantial amount of side effects but if you're a child, maybe looking into getting this vaccine on a yearly basis, for which we have absolutely no data, we have seen for the live vaccines that beneficial non-specific effects are boosted with each dose of live vaccine but we also have indications for the non-live vaccines that the negative unspecific effects get worse with each dose of vaccine.

From my perspective, one should be very cautious with giving this vaccine year after year after year to children who have, for all we know, nothing to gain from the specific or very very little to gain from the specific protection against COVID-19.

SR - Why do you think critical vaccine research is so taboo. Why do we have this situation in medicine, where you can't even slightly question anything to do with the vaccines, where we're supposed to pretend like they can only ever be beneficial and positive and can't ever result in harm? We don't think this way about any other class of drugs, we realise that they have benefits and they also have harms and those always need to be weighed against each other but when it comes to vaccines there is no balanced thinking at all, we're just completely uncritical. Why is that do you think?

CSB - There is something very unfortunate happening in the debate. I think there are two extreme groups and they're actually quite small but they have been allowed to dominate and these are the extreme anti-vaxxers who are saying vaccines are bad, punctuation mark. They are not interested. I talk with them, they might cherry-pick our results on negative non-specific effects but they completely dismiss the results on positive non-specific effects, beneficial non-specific effects. They're not interested in the science, they're interested in cherry-picking the parts that fit into the narrative that vaccines are bad and harmful and you should never take them.

And then, I don't know what came first but there is just as extreme group, in my point of view, which are pro-vax and I'm saying that with just the same sentiments as I say antivax because these people are extremely science resistant as well. They will not look at our data and look at them from a scientific perspective, they will dismiss them, they will look for the error, the reason to say this is rubbish, this should not be taken serious. They will try to attack me as an anti-vaxxer for proposing anything like that so, you know, smear me or anybody proposing this kind of nuances.

So they're just as religious as the anti-vaxxers, just in the opposite direction and somehow we have some kind of centrifugal forces here, that has forced the debates out into these two poles where there will be on one side, those saying vaccines are bad and the other is saying vaccines are good and they have stolen the whole centre court of the field where we really should have the debate and where I think most people are, where they like to look at the signs, discuss pros and cons and a large majority on the centre court are super positive around vaccines but also acknowledge that they can have side effects.

And then there are some people who are generally sceptical about vaccines who can see that and don't dismiss that they protect against severe diseases but are more concerned about the side effects. This is really between these groups of people that the discussion should take place, that we should look at the science, discuss pros and cons, design new studies which could help to resolve any doubts etc. I guess it's also happening in politics. There are areas where things get so polarized that it's hard to get back to the sensible conversation.