Immunology with Professor Robert Clancy

well a warm welcome to this talk thank you for uh for logging on i'm just delighted to introduce emeritus professor robert clancy from sydney australia that's right isn't it you're in sydney at the moment i'm in sydney yeah that's right yeah nice and warm yeah clinical immunologist in fact pioneering clinical immunologist i believe you were one of the first well were you the first senior clinical immunologist in australia well i there was no training program when i started so two or three of us got together and said look let's make it something yeah that was a time when when the the british were very laboratory orientated you might remember with people like a long time ago yeah but so you actually started doing it clinically you're obviously a medical doctor um you you've specialized in infections of the airway and the gut and what i'd never heard of until i started preparing for this is the the gut lung access which i'd love to talk about later you've developed a new vaccine uh in the mid 80s was it for acute bronchitis vaccine that's correct yes yeah yeah you're you're a physician and a pathologist how you managed to do that in one lifetime bemuses me but it's it's amazing um your medical researcher i did check 260 publications uh is that right that is a lot more than me let's just leave it at that uh nearly 6 000 citations which is amazing uh foundation chair of in the university of newcastle that that's obviously the one in uh australia in pathology a pioneer in the field of mucosal immunology which i hope we're going to learn in this uh talk you've developed treatments for copd therapeutics you're a doctor of science and of course a doctor of philosophy and you've got the order of australia the the order of australia medal i mean if we went on it would take up the whole talk so thank you for coming we're just delighted that you've come thank you so the first thing i'd like to talk about is is covered as a mucosal disease and this idea of a mucosal compartment is kind of new to me could you sort of what is the science behind that i think the best way to look at this uh john is to look at the fact that most people who do immunology 101 and we all do a little bit of immunology we're talking about the immunology that protects the the body that keeps all bacteria or virus out of the bloodstream and we call that systemic immunology we read about igg antibodies every day but the reality is that covet infection like influenza is an infection of the mucosal surface of the airways and if we're good we keep it there and and a very different type of immunology had to develop because all of a sudden you've got a situation where there's lots of bacteria lots of virus very different to inside the body which is completely sterile and so you have to have an adaptation of this mucosal immunology which did so quite separately so you have these two compartments with very little crossover between them and the greatest difference between the mucosal immunology is that you need a mechanism of down regulation of suppression otherwise you'd blow up with inflammatory response to all these bacteria and virus which we we now talk about as the microbiome that that's the essential difference i think i'm kind of getting it now so the inside of the body is completely sterile we have almost have an internal immune system there and as you say we know about the igms and the iggs that are produced in in response to antigens getting under the skin as it were but but we've got this extra sort of immune system that's patrolling the surfaces of the body almost so the mucous membranes were thinking about that lining the nose that produces the mucus like lining the pharynx the the the airways and because that's exposed to this milleur of of uh infectious or potentially infectious agents outside it needs its separate its own separate immune system really exactly and covert of course is an infection of that compartment and the whole aim is to keep covert there if it starts leaking out down into the gas exchange part of the lung which is recruits the systemic immune response that's when you get very sick and a pandemic for flu or the coronaviruses is essentially when one of these viruses learns how to get out of that mucosal compartment and gets down into the gas exchange apparatus recruiting what it doesn't want which is this systemic immune response right so so when i had flu it started in my mucous membranes i remember i had a really bad flu in 1919 i thought it was going to die it was awful yeah that's because the virus got from my upper airways down into my alveoli where you're talking about tiny tiny thin um the lining of the alveoli the endothelium microscopically thin the virus can get through that and then and then when it gets through that and gets through the the lining of the capillary it's actually in the blood then isn't it it it can be exactly yeah and then the virus will go around the body and that will generate a systemic inflammation is that is that the thinking that's that's essentially right the the covert virus and the flu viruses can create all the problems most people get who who get quite sick without actually disseminating through the rest of the body that that of course can occur but that's a light phenomenon that's in people who are seriously in hospital intensive care yeah yeah but there's kind of a difference here isn't there that there's the potential for the for the actual etiological organism or virus to get into the blood and there's the potential for the immunological reaction of the body to that virus to cause a systemic inflammatory response syndrome such as the acute respiratory distress syndrome where the alveoli fill up with fluid am i right in thinking there's two ways to make you sick there what what you're doing uh john is is encapsulating the whole issue into the post-parasite relationship the relationship between that the parasite which in covert is a virus and the uh host which is the immune response and it's that relationship and the outcome of that relationship that determines the outcome in that particular patient indeed so this mucosal immune system just give us a bit of an idea of what are the components of it i mean i know immunoglobulin a's tend to live in in the mucus as opposed to in the blood but i'm not familiar with any any sort of of the cellular components of the immunity in the mucosal system what sort of things are we talking about there and are they innate are they specific are they acquired are they adaptive yes conceptually there's no difference between the systemic and mucosal immune response you have the generals which are the the smart people telling the immune response what to do the t and the b lymphocytes which most people have heard about and then you have the foot soldiers who are recruited to do whatever the general tells them what to do it's just that the generals and the foot soldiers are a little bit different at the mucosal end to the ones that are in the bloodstream and the spleen and the lymph nodes the interesting thing about the airways is that it's an extraordinarily uh fascinating system whereby the lungs have one job really and that's to move oxygen into the body carbon dioxide out anything that comes between or interferes with that action is a problem and so uh the the body has developed a system where it generates the factories for developing these protection mechanisms are in the gut and this is something that i think has been completely lost in the covert story is that when you get viruses and bacteria in the airways it gets dumped into the gut all the time we're swallowing a couple a cup full of secretions every day and not knowing about it normally it's only when you exceed that you start coughing something up and so everything is getting dumped and the factories that make the generals the t cells and the b cells for that mucosal immune system are in these little lymph nodes in the wall of the gut called payers patches and when i was a medical student and when you were a student john the batch was something you didn't have to know anything about because no one else did either well we had to memorize that they existed i remember that that gave you a higher distinction for some biology examiner these are actually lymphoid tissue aren't they they lymphoid tissue like a lymph node and and so the virus comes down and is taken into these in the upper part of the small bowel and then the t cells and the b cells go and they've got little postage stamps saying take me to the lungs and so it specifically comes back to the lung to do the protection and it generates the innate system just as the igg says it's a slightly different innate system and there's a lot of misinformation going around at the moment where people are saying oh look in covert we're destroyed vaccines we're destroying the innate system they completely forget the big picture that what the innate system if it's not there or there it depends on whether the generals telling it to become organized and so it's understanding that big picture that's so important in understanding covert wow so the reason you get immunity to a respiratory infection is because you are swallowing the virus or the bacteria or whatever it is that's recognized by these uh these immune areas in the gastrointestinal tract the cells in the gastrointestinal tract are then directed to the lungs where they generate the immune response exactly that's incredible i didn't know that it's just amazing now john you're in good company when it comes to curving well it would appear so it would appear so there's been there's been quite a lot of hot air over the past two years it must have been uh almost intolerable for you to listen to the uh the anti-science i think we should just say that the reason i was so pleased to have you on is because i mean you do it a completely different level to me but we both believe in helping patients that's correct we both believe in applying science to do that we both believe that that science has to be accurate and has to represent some sort of truth and has to be empirical and uh you've done that at a world leading level and all i've done is teach it for a few years but i think i think well i think the other thing john is we're both keen on teaching it we we want people to share that knowledge yeah absolutely very much so so i'm getting this idea of covert as a mucosal disease um and and it's it's getting into the it's becoming systemic but by the gastrointestinal tract is that is that what why was i so sick when i had influenza then what actually triggers triggered my sort of systemic inflammatory response syndrome to make me feel so bad what made you feel bad and i ended up in singapore hospital with the same thing so i know what it's like yeah his extraordinary uh response of the body's immune system to the virus basically getting out of where we'd like to keep it it moving into where you can get a a systemic immune response usually that means it's going through the conducting airways into the gas exchange and so all of a sudden the immune system switches from the mucosal response in the conducting airways to the systemic igg type response the all over full bodies all these cytokines and molecules that's what people focus on these days they talk about without understanding how it fits into that big picture but that that is true is it that the immune set my systemic immune cells will release in pro-inflammatory cytokines absolutely that will go to my brain and that's that's a big part of what makes me feel so bad isn't it absolutely and you can measure these in the blood yeah but then again it's good that i feel bad in a way because i'm going to lie on the floor groaning rather than go out and go go exercising hunting or farming or whatever because it's going to stimulate my heart and cause ventricular fibrillation or something like that it just kind of makes sense but yeah it's it's an immobilizing yeah indeed i was lying on the bedroom floor and couldn't get into bed it was terrible oh i was i was giving uh a series of talks to the south east asian physicians and i wasn't there for two days they found me lying on the floor trying to get to the shower i mean it's it's really uh horrendous yeah yeah and then you have other cytokines that um generate fever you'll have other cytokines that generate catabolism to break down proteins to mobilize to make antibodies and and all this is part of the body's natural way of overcoming these potentially life-threatening infections that's right i mean cytokines are just very small molecules that are messengers uh going from the the smarts to the less so smart and getting things to happen yeah it's it's quite amazing isn't it you could write you could write a book on this couldn't you people do yeah right now the implications on this now before i ask you this question we want to notice in passing that you have personally developed a vaccine uh for for treating um acute bronchitis now what i did john was i uh i was part of the the first groups that were looking at how this system between the lung and the gut works and it seemed to me that if we could get a large amount of bacteria and inactivate it and make that system of protection work optimally then that would be a good thing and that's what i developed i just simply developed a way of enhancing and optimizing that protection which is probably very valuable in people who are older like me maybe yourself over 60 that over 65 you turn off that immune response and the reason that people get very sick over 65 is that they have a slow mounting of this immune response allowing an expansive overreaction by the innate immune response and so what i was doing was developing a way of shortening and making more efficient that process and we were able to reduce hospitalization by 50 percent in people with um chronic lungs it was quite but of course no one's interested in it because it's such a simple useless type of product the pharma companies hated us yeah i noticed you said that's all you did you just reduced acute hospitalizations by 50 percent i'm impressed well yes it's an interesting point though isn't it here because the the the the treatments that get uh globally diffused are those that can potentially have some uh return we think of fellow australian dr barry marshall of course with his helicobacter um by lawyer which wasn't well received by pharmaceutical companies because he could actually cure people yeah well no very quite well i don't feel too sorry for barry i know i'm not no but it's it's it he did have some early opposition i remember that very well yeah i i remember it very well it was an incredible uh incredible feat yeah and of course he experimented on himself which was really quite quite quite quite mind-blowing so my point is you you you are able to look at vaccination objectively so implications of the co covid as as a as a mucosal compartment disease what are the implications of this on on the vaccine strategy as it's being practiced today okay well when we began this talk i emphasized that a major difference between mucosal and systemic immunity is the generation of suppression mechanisms aim to suppress the inflammation that would otherwise blow up the body now this is a story that goes back to a chap called sulzberger and chase back in pre-1950 it goes back to the whole area of oral tolerance for the pediatricians wondering why people don't get uh sensitivity to foods knowing that two percent of all the proteins we get into the bloodstream and the body has developed this system where you down regulate response and this is exactly what's been happening with covert all of us have been getting coronavirus infections over many years every time we get these infections a little bit goes down into the gut and you're stimulating not just an antibody and we know that most people who get coveted have still got residual antibodies against the corona the normal seasonal corona virus and they probably have a little bit of protection but we also know that you stimulating suppressor mechanisms so it's all about a balance between the positive and the negative and so all of us have in our lymph nodes in our systemic immune system existing immune responses that protect and immune responses that don't and some of the early work that my group was involved in was showing that these are two sequential waves now what we're seeing and i think the best data is probably the british data the danes have shown something similar you you'd be very familiar with a lot of this is that after about six months and this is what a lot of people couldn't understand the vaccines aren't working very well um and they say well maybe it's a it's all micron or something like this but in fact the reality is you're starting to get this down regulation and people are saying wait a second this is not like a measles vaccine it's like a flu vaccine and the flu is a very good analogy what you see with flu you're seeing with covert and and the current situation of giving lots of fairly sort of panic reaction um boosters is that we're starting to get a situation where we're getting a bit like food we're getting a non-responsive uh systemic immune response and this of course is the reason why we're starting to see in some countries more infections than we might expect we we're hopefully still getting the blunting of the serious because we're shifting away from serious to less serious infections but the down regulation and i think the concern is um i was just reading something about the fourth vaccine in israel you might have seen john that uh it looks as though they're getting antibody but they have to be very careful you can't relate anybody to protection it's a surrogate parameter something that helps you get an idea of sensitization not necessarily protection and so you have this situation whereby um people are saying wait a second this is crazy we're giving more and more vaccine but we're getting less and less benefit i think just looking at your own uk data from the the first boosters um my reading is you're probably getting protection running for weeks maybe a month or two yeah and then you're back and people say wait wait a second we got six months the first time now we're getting uh just a couple of what's going to happen when we have the next one and the next one and so my driving um compulsion is that we need to look at plan b i'm an immunologist i'm all i'm certainly a very keen vaccinator we need to do it scientifically and we may need to bring in strategies with using widespread early treatments that are cheap and available which i suspect i'm not allowed to talk about on this program but we all know about them and we know how effective they are and to me that is where but we're not getting this information transferred to the decision makers in the way in which i would like to see happen i have never heard once anyone talk about why it is we're getting a turn off of immune responses and it's it's there's this whole prison it's not it's not secret um it's all about the mucosal tolerance this down regulation that you stimulate a positive you stimulate a negative and the balance determines what you see does that make sense to you it does and this is exactly the data i was actually looking at yesterday that were the first two doses of vaccine you've got a a fairly good risk fairly good protection against uh symptomatic illness for about 20 weeks exactly after the booster it's down to 10 weeks that's right so presumably if if we extrapolate the graph the the the fourth dose in israel we're probably looking at protection for only five weeks i think that's what they're seeing that's incredible and the way i think about this is of course we have these lymphocytes in the blood we have the the the large and the small and the small ones we've got the b and the t but the the t we've got the three types haven't we we've got the t helper cells we've got the t cytotoxic cells that directly kill virally infected cells we've also got the t suppressor cells that's right so what i hadn't realized and this i really appreciate this what i hadn't realized is that vaccination can stimulate all three types of cells that's right and i i like to think of it even more simply john in saying that when you stimulate immunity you're actually stimulating protection suppression facilitation of infection and auto immune responses against white proteins represented through the body so and it's the balance of all of those at any time that will give you what you see and and that's exactly what we're starting to say i think we've always been seen uh in this infection yeah it's just that it hasn't been obvious until you've mentioned it today this is the first time i've i've realized it so so when i eat peanuts maybe two percent of those two percent of that protein can get into my blood as peanut protein exactly then why why why on earth don't i make antibodies to that peanut protein and therefore next time the peanut antigen will interact with the peanut protein antibodies and i'll get a severe allergic inflammatory reaction well yeah and it's the surprise is it the suppressor cells that stopping that from happening yes it is and in fact we call that food allergy uh food allergies are where you don't get the balance right and you haven't learnt to suppress that response because you are getting small amounts of the peanut actually it's a very good example because there's been some very good studies where um a couple of years ago someone said well wait a sec if all this is true if i feed peanuts to children who are high risk of developing peanut allergy yeah then i'm going to boost the suppressor compound and that's exactly what they did getting back to an issue you just mentioned which i think is concerning is how long if you build up with repeated injections suppression which makes you prone to covert how long does this last and i was thinking about this last night i think you'd ask me that question how long does the suppression last but how long does the suppression how long thank you john good question i'm just about to ask that yeah okay well if you look at the peanut story it can last years okay what they do they feed the pediatricians fed these children several hundred of them yeah every twice a week large amounts of peanut and they built up a tolerance they so they didn't get food allergy and when they challenged them a couple of years later they still were not getting it now there's a lot of reasons for this um but it's it suggests that we have to be extremely cautious about our vaccine strategy and i think they got it right with flu more by accident than good measure by bringing in seasonal injections once a year so it is physiologically possible is what we're saying immunologically possible that a vaccination could promote long-term suppression absolutely absolutely and i think it's more than this because every every year we get coronaviruses and we're stimulating this through the gut and i suspect that's why we get the uh tolerance um from after we have covert is that we're actually swallowing this and it's going through this remember we talked about how the the machinery for developing immune responses in the airways is in the gut the machinery for developing the down regulation is also largely in the gut and responds to the same specificity same rules of of immunization so why is it that so i i've been exposed to four natural corona viruses on a regular basis that's right why why has exposure to those natural corona viruses not down regulated my immune response to them i think it it probably has and that's probably why you only get a very different antibody response if you like to a a covert injection than a measles injection if you look at a measles injection or any other cis mumps or rubella you get a big igg antibody response and then you give them another injection and you get a bigger one yeah because they're not subject to the same level of suppression as a mucosal immune response it's that covert starting off as a mucosal infection that determines and dominates the longer term outcome and influences everything we're seeing not it whereas the measles goes through the blood and stimulates the systemic immune response first up right so so the small pox that's that's been eradicated the measles the mumps or all all of those things when they're injected into the body the antigenic nature of that material is more likely to stimulate the um the the t helpers cells that are going to stimulate the b cells to produce antibodies rather than stimulate proliferation of the t suppressor cells yes there aren't so many of the two suppressor cells there because got it got it i think this is finally getting through into my uh learning difficulties here it's it's the the the the the mucosal immune system has got to be like this because we're exposed to every protein under the sun on a regular basis you would blow up you otherwise would be allergic to milk and eggs and cheese and basically every sort of protein that's exactly that's out there or every allergen that happened to breathe into my lungs every pollen which of course is true take that idea and you ask everybody watching this what do you do when you have these oh we have either desensitization injections or we give it under the tongue and what that does of course is gradually increase your suppressor cells in the same way as having lots of injections so there's an analogy between all of these uh observations so for desensitization therapy it makes much more sense to actually give the material exposed to a mucus yes surface of course is what's happening these we've now moved it used to be mumbo jumbo stuff uh you know the units and throat doctor would grind up his house thus might yeah he drops out of the tongue and young academics like me would come along and say morty naughty but of course it's turned out to be right yeah yeah yeah no not right so this is this is this is what i didn't understand the fundamental difference between the systemic immune system and the uh and and the muco is am i right to say mucosal immune system is that a good word exactly and the whole aim is to keep that virus in the airways where it controls and this of course is why you can have people with asymptom asymptomatic infection lots of antibody and their blood from vaccination but they can still transmit the disease because they're not subject to that systemic immune response that only comes into play when it starts the virus starts trying to get out of that mucosal compartment into the airway into the gas exchange so it's quite possible to have lots of virus multiplying in my mucosa some antibodies in my blood to it but the antibodies not getting from the systemic compartment into the mucosal compartment therefore i can still be uh infectious exactly there's a little bit of leakage but you're absolutely right and and this explains why people who are vaccinated can still become asymptomatic or mildly infective and transmit the disease of course yeah exactly yeah so so the these t and b cells actually live in in in the mucous in the mucosal yeah in the in the mucosal um the the lamin appropriate the lining tissues of the of the airways and the gut and then the b cells all sit there producing antibodies that actually diffuse into the lining mucus exactly the and as you said it's a different to the igg and blood it's an iga and that has very igg is a pro-inflammatory antibody activates complement all the foot soldiers whereas iga doesn't do this iga acts all by itself to minimize inflammation so you've got igg pro-inflammatory bring in the foot soldiers iga says well wait a second i'll just bind to the virus and neutralize it but i'm not going to activate all this complement and things because it's localized to the surface exactly wow that makes perfect sense when you say that so what are the implications of this what actually happens in in uh sepsis when we get this cytokine storm well there it's a very good example there you've got invasion of the bloodstream however it may come from the renal tract wherever and you get this massive systemic immune response remember it cannot tolerate back bacteria or virus in the air in the blood and so you get this massive exaggerated unregulated unsuppressed no suppressor cells and so you're pouring out the cytokines and these cytokines which are good in an appropriate place in an appropriate amount becomes incredibly damaging when they're just let loose and so you've got this uncontrolled response which you do not see in a mucosa when when you see it happening uh which is going back to what we used to do when you see it happening in the airways the overreaction is coughing up yellow sputum in people who have got chronic lung disease um they've nothing to do with systemic immunity they get this inappropriate response which becomes a little excessive and they're just producing more white cells and the more white cells go into these make it look yellow and people they have an exacerbation of copd and that's what we're we were able to stop that by optimizing the protective mechanism wow yeah that is that is uh that is quite uh quite incredible um the the import the importance of uh combining vaccine with early drug treatment um but a bit of a controversial area um but i suppose i don't know that we're probably not allowed to talk about particular drugs but what what is the difference between the the the prophylaxis that uh a vaccine will give and early treatment of the virus or early treatment of the inflammatory response that the virus is generating yeah i i think these mustn't be looked at as separate they work together there's always going to be a role for vaccination just as there is a very important role for early treatment what the early treatment does it reduces the load of virus and if you think of virus in an unrestricted way increasing the amount of virus then clearly it's going to move outside of the the bronchi into the gas exchange it's going to be activate a much greater response and so to me to me the the only logical way of handling problems um and i'm not alone of course in this is to help the vaccinators and i'm a vaccinator help the vaccinators come up with a logical strategy for vaccination by using early drug treatment whatever's considered the most appropriate um early drug treatment so that you particularly with the omnicron which is looks i i hope is a transit zone into seasonal affections and some of us are thinking along those lines um that we help move towards um spacing of vaccines so that we do not accumulate what downstream could be incredibly damaging uh if we turn off and we basically make coronavirus like eggs or house dust something like this so that we never make a response to it and we may be in for really serious problems if we do that and so i think you we should be using everyone should have at home their you know the early diagnostic kit the uh treatment i mean it's so logical we can do it in poorer countries but we seem to have a problem doing it in our own um as you know the politics better than i do yeah so the the the the when when doctors first get started the nurse and doctor started getting sick at the early starts of this pandemic what i thought was they would get a very high inoculum a high viral load um for example if you're doing endotracheal suction yeah yeah you could get massive aerosolization of the virus um the the clinicians could breathe in a large number of viral particles until billions of viral particles that would infect many millions and millions of their cells all at the same time all of these cells will start producing viral particles all at the same time so they'll end up with a very high viral load that will get into the systemic immune compartment and that's what could generate the really severe immunoglobulin g pro-inflammatory cytokine uh acute respiratory distress syndrome and all those other sort of sepsis related things that all that will force it does that make sense is that false i think it makes sense i mean yes it does make sense yeah um whether that i mean there are so many variables in john in terms of um determining that total load i mean it depends on the genetics it depends on your previous sensitization the particular experience all of those sorts of things but in general terms of course the greater the load the greater the chance of getting significant infection so with omicron um is omicron intrinsically less likely to get down into the lungs because presumably if omicron's up in the upper airways we're still going to swallow it aren't we exactly so we're still going to get that sort of systemic effect because we've swallowed it and it's going into the pairs patches in the lungs so why is it that if we're still swallowing the virus that the omicron is causing less and i think we can say now omicron is causing less severe disease how does that sort of fit in with this thinking oh i think john that's the reason you and i and others are thinking that maybe this is a transit zone we're seeing um we're seeing a mutant which has less capacity to escape from the mucosal compartment and so the symptoms they're getting uh local they're getting cough right uh they're getting sore throat but they're not getting that pro-inflammatory moving out of that passageway into the alveoli they're not moving into that um and maybe we know that one of the reasons that um the the early covert variants got into the alveoli is because the receptor systems are more diffuse there are more receptors in the alveoli and so it's easier for them to go it may be simply that the uh multiply uh mutated spiked protein of omnicron um is less capable of binding to receptors and so therefore it's going to penetrate less this distance it might be something as simple as that yeah but but whatever the mechanism we are seeing uh a much more mucosal compartment disease yes it's restricted yeah yeah because what i was confused about is that i was thinking if it's a mucosal compartment disease then presumably it's not going to stimulate the systemic immune response but i think you've answered that question now because it still stimulates the mucosal it's exactly and what i didn't say before which i should have is that when it goes to these pious patches it's not just going to have cells directed back to the lung some of them have got igg receptors on them and so you'll populate all the lymphoid tissue to an extent and that is why you get the systemic suppression you've got the suppressor cells spread and you need that when you think about the food allergy sure that you're not going to react to every egg you eat so you actually end up with these suppressor cells in in the lymphoid tissue in your armpits and your groins exactly right whether it's delta whether it's alpha exactly wow yeah incredible and so but the the the more of the the third question there really on the early treatment was that the lower we can make the viral load the better exactly exactly and as well as that some early treatment drugs could be limiting the immunological response uh should that become should the inflammatory response exceed the suppressor response exactly early treatment could prevent that and therefore prevent some of the inflammation so so there's really two ways to attack this disease attack the virus directly and attack the pro-inflammatory response of this virus and both of those can be done with the appropriate early treatment therapies and by combining the the vaccine strategy with the early treatment strategy uh i think we're going to be very quickly i would like to think we're very quickly out of the terrible situation we're in at the moment so this is a synergistic approach to medicine isn't it it is that is the vaccine and the early treatment there are not a lot of synergistic people involved in making the decisions it seems well i'm hoping there's going to be a few more after if a few people watch this watch this video would be the hope um now these vaccines that we're using now we could call them genetic vaccines whether it's the adenovirus vector dna vaccine or whether it's the the the um mrna vaccines they're both genetic vaccines essentially do you think we're missing an opportunity here but by not exploring classic uh antigen vaccines that maybe generate a much more polyclonal response yeah well my views on this are very clear that the genetic vaccines which is a term i also use genetic vaccines produce unregulated amount of antigen in the body you have no idea how much we know it circulates in blood for several weeks maybe in micro particles for a lot longer we know it's represented throughout the the body it's appearing in all sorts of uh um tissues post-mortem studies uh people dying up post-vaccination are showing um the spike protein in the in the lesions in the blood vessels so we we know this um one of the things i was thinking about also last night was that maybe with um the vaccines because we're expressing unlimited amounts of antigen maybe we're also swallowing some vaccine some of the spike proteins and that's affecting tolerance i don't know but i don't think it's been looked at but the the the but the reality is that um we have absolutely no idea how much antigens in the body what it's doing to our immune response uh and it'll be very very interesting to see with as nova vacs and some of these uh protein protein based uh antigen based uh vaccines as we start getting experience are we going to run into the same level of immune non-responsiveness with that we're seeing now with all the genetic vaccines we don't know the answer to that um my i don't think it'll probably make too much difference to that because i think that's but it might i'd like to think it might but i don't think it will but if you're giving a protein-based vaccine you're giving a precisely measured dose of antigen aren't you tiny little weeny bit of energy exactly and you know exactly how much and the body's not going to make more of that antigen exactly and it's going to be pretty much limited to the lymphoid tissue although it spreads a bit but not much exactly so as we've said spike protein has been found in in the uh the endothelium of blood vessels exactly um does that mean do you think that the the the recipe if you like the the the adenovirus vector or the rna micro particles got into the blood migrated into the cellular endothelium and the vaccine stimulated the protein producing mechanisms in the vascular endothelial cell i think that's the the logical understanding but you know we're at early days we we know so little about these vectors i know it's very trendy and whatever but people forget that when we had the 57 and the 68 flu pandemics they made traditional vaccines within five months five months of those uh the appearance of those novel mutants and so the argument that all we've got big advantage with messenger rna vaccines it really doesn't hold as strongly as the big companies would like us believe the um i'm very concerned about the um about the the genetic vaccines we there's a recent study where they tried to make a flu vaccine with the messenger rno which you might have seen and it was no different in outcome in antibody production than the traditional one so i think that we really have a lot of work to do if we're going to start immortalizing messenger rna vaccines uh in our in our um medical uh armory it sounds like a very useful potential tool in the toolbox if you like but not necessarily the only tool we'd like to use i didn't know that in 1957 they produced vaccines in five months yeah by the end of 68 1968 that is incredible yeah the interesting story in late 1957 my mum was so sick when i was a baby she couldn't get out of bed and mcgran came and took me away i know she got me in the plate and she took me away when i was five five months old i think i was and yeah that makes me a little harder than you john but i remember but both my parents were so sick they couldn't look after me you know it was i was the the mortality it's interesting going back and look the mortality was point five percent in it back then yeah and that mortality is greater than we're seeing with the omnicron barrier yes yes yes absolutely yeah yeah so in 1957 they cultured up a load of viruses using some sort of cell culture was it maybe an eggs or something i don't know yeah kidney cells monkey kidneys oh that's right that's been around for a while yeah so so the the culture of those up produced untold billions of viruses attenuated those viruses and just injected the virus well no they were using eggs for that they were using they were still using eggs i thought okay right right so but basically they took the vite they they bred up the virus in eggs they they they killed the virus simply injected the whole virus the whole day exactly just like some of the vaccines around today yeah and yet today everyone's mouth enough because we produced a vaccine in what 10 months it was more than five months wasn't it i mean more than it was we didn't get the first vaccines to what was it december that's right december 2020 so that's that's basically the best part of a year that's right so so in the last 64 years we've learned how to make vaccines twice as slowly you're becoming a cynic john us surely not it is interesting interestingly though the chinese vaccine was uh an attenuated or killed well that's right i i don't know a lot about it but my understanding is it's an inactivated virus yeah and that i think appeared before the uh messenger rna once again oh yeah yeah yes i i absolutely i mean it's not significant or something yeah yes it's cyanoback that's right now the the the other thing that's interesting is that the the uh the adenovirus vector vaccines obviously the adenoviruses are virus size of course and the the micro particulates that they wrap the messenger rna and are also viral size and my understanding is that the the the body reacts to the physical size of these particles in the blood because if you have a virus if you have a particle of a particular physical size the body thinks that's a virus and therefore you can get an inflammatory response to it so so my question is and you probably know this is one of my hobby horses if you had a larger intravascular dose of adenovirus vector or rna vaccine is that more likely to cause a potential systemic effect because you're getting a large dose of the vaccine going directly into the bloodstream i think the danger would be the level of sensitization at the time you give it um i mean it's a bit like uh any intravenous antigen if you give that and the person sensitized you can get anaphylaxis very quickly but having said that look i don't know the answer to that question i i'm fully aware that particle size um and the way in which whether it's got a lipid that will actually get into cells more easily which is what they're trying to design all the time the level of of intrinsic uh adjuvant that make it work better all of these things come together and of course uh vaccinology is a pretty sloppy science with great respect to my colleagues who make these that you know because there are so many variables and to to try to dissect out the variables and then you do it in a mouse and you say well is the mouse the same as man and so there's there's a lot of empiricism i think that comes in vaccinology and of course we all love modern technology uh i can remember when my son left home technology walked out the door um he probably had the same experience and here we are using all this technology but um it's when you look at vaccines um some of the best vaccines are some of the crudest of vaccines you go back to what we still give our grandchildren uh and and they're getting um the same vaccine that i had when i was that age uh tetanus toxoid or uh yeah we've improved a few like whooping cough but by and large it's it's it's pretty pretty basically the same yeah yeah every day on a a e i worked for three years part-time on a e when i retired from education and i must have probably i must have given oh i don't know probably average three or four a day injections of course of course so my point i'm trying to get out there is do you think there is some merit in advising aspiration to prevent intravascular inadvertent intravascular administration well um i know it's not in the i think i think it would be brave a brave person to go past the suggestion stage i mean i think you're very keen on aspiration for immunization aren't you um i i i think that even in the deltoid where it's less likely yeah that there's about a one chance in every two or three thousand injections that you could give an intravascular injection if you're doing that uh we have evidence that um people are getting more side effects from the vaccine so i mean i i would think that that you have to have a very balanced approach and think it through but i understand the theory of what you're saying sure but i think that there are practical issues that might uh might make that a difficult well there you are john it's a new company you can start um no i don't think so probably i mean i trained student nurses for well full time for 27 years and you know another 15 years on top of that and i always said you stick the needle in you draw it back and you know just to see people not do that i kind of find it difficult now here you're saying let's let's put it directly into the vine i'd rather not do that i'd rather put it into the muscle where it's going to go into the cells to generate the to generate the the antigen so so that the antigen generates the immune response in the artery and we're not getting expression of spike protein say from the myocardium which would then attract an inflammatory response to the myocardium which we certainly do not want we do not yeah certainly not yeah can just another just a quick question that would help my thinking here how does how does colostrum play in into this mucosal immunity when you know when the baby's first born in the colostrum for the first few days really interesting because um i just saw the other day uh study on breast milk that you might have seen um where um there was no evidence of i think virus in the colostrum but if you looked at antibodies i bet you pounced the peanuts that you would find antibody because colostrum what we didn't go into was how i got into mucosal immunology with john boehnerstock in canada at mcmaster university uh john came up with the idea that there was a common system between all the mucosal surfaces and that's how i my entry point was injecting the rabbits i think but what we showed was that the cells that come from the past patch with the postage stamps postage stamp says go to the airways but also says go to the reproductive system go to um the gut go to so you've got this system of and go to the colostrum go to the the ducks in the breast for the um and this is the way the baby can actually get some of these antibodies that they would like to get this is why one of the many reasons why breastfeeding is so important yeah that's amazing so so there's actually a chemical signal in in these cells in the past patches in the gut that literally tells that cell to go to a particular tissue yes it puts it puts a receptor it puts a binding protein that will go to any tissue that has the right receptor it's a docking system yeah yeah and so you can see here's the paste patch and out comes the t cell and the b cell and it might say hey take me to the lymph nodes and i'll have a systemic immune response that might say take me to the um all the mucosal tissues the breast the respiratory tract the upper respiratory tract the gut and we'll protect and so um the ones that have the postage stamp going to the breast will make an iga antibody the ones that have the postage stamp taking to the lymph nodes will have igg antibody so these are different ligands essentially that must be made to fit a particular receptor that is specific to a particular tissue exactly yeah exactly isn't the body amazing it's just just incredible do you think in in the states for example there's only a three week gap between the primary and the secondary dose would you like to would would your intuition that that could be a bit longer yeah i i think that's a panic reaction it's a concerning panic reaction and it's because they do not have people that really understand uh i won't go into personality but i actually know a lot of these guys uh for many many years and um their understanding of immunology is very different to yours and mine now i won't compare your understanding and mine by any by any means at all but it's in it's interesting that you get people in these very senior positions yeah who don't really seem to understand their i'll tell you some stories off camera yeah um is there any contenders on camera probably not probably leave that one no we'll leave that one my apologies for trying to be provocative um i think that's answered most of my main questions actually uh robert i mean it's just um you know whenever i do these uh talks with people you know people that actually know the field like you and my mind's just reeling with the with the just amazing nature of the science we've been talking about and it just takes me a while to just to sort of come down after that it's just um well i think in this area this is not this is not rocket science it's not new but i think it's been sequestered away away from the people who are working in covert if you talk to some of the pediatricians interested in food allergy they'll tell you the same story and it's just a matter of taking that basic science which has been around for probably 80 or 90 years you know very primitive form and adapting it to what's going on uh in in covert and um to a large extent that well let's just say that hasn't been happening to the extent we would uh we would like uh sadly not yeah how have you been personally robert have you had uh have you had uh omicron's rampant there at the moment have you kept well we yeah well a bit of luck we sort of hit the peak and it's on the way down um all my family seemed to have my my my daughter rang last night to say she thinks she's got it my son's just got over it we've had a lot in in this environment uh christine and i haven't had it but uh um it's uh um you know in many ways i thought i had it and i was terribly disappointed to find when i looked for the nuclear capsule to anybody it was negative that's okay yeah the specific antibody okay but it is inevitable i mean i was very surprised if you hadn't been exposed to it oh i think you're right absolutely right just thankfully we've got a delayed response here i think we we had a pretty sort of uh um uh pretty rigorous lockdown process yeah oh very yeah and it's been very destructive economically and psychologically but what what i think we're seeing is a bit of catch up we have one part of australia called western australia well i hate to think what's going to happen over there i just noticed today they're starting to get increasing numbers there is a little bit of community transmission now in perth i think but just a little bit you know i sort of it's just starting to happen i would imagine that there will be an exponential growth over the next few weeks and we get a very similar curve to the curve you've just seen in uh in victoria and new south wales that's right i guess in a sense the those who make these decisions would say okay we've we're getting this delayed response but we're getting it with a less pathogenic organism i guess that's one argument they can make isn't it fortunate that omicron is less pathogenic than delta right no well i i think that's it's not surprising john i mean if you look at if you look look at every pandemic we've had certainly in in my part of the world right from the bubonic plague in 1900 right through all the flu ones they're basically all over within two to three years every one of them and um it's because to me a question becomes have we distorted that natural sort of resolution of a pandemic by um what we've been doing in treatment the way in which we've been vaccinating i don't know how are we delaying uh our move for natural immunity which which we're starting now to see throughout the western world and much of the non-western world um which we know is is better than uh than the immunity that follows a vaccine yeah i mean my thinking is that uh i'm going to be exposed to omicron there's maybe 20 25 antigens are going to generate an immunological response that'll affect my antibodies my b and t cells i'm expecting that that's going to give my what i now understand is my mucosal immune system one heck of a boost exactly and i'm going to be and because it's so polyclonal i'm expecting that i'm going to enjoy immunity to a wide variety of possible future well i think that that's exactly happening it's uh my understanding is that those who have had omnicron have significant uh immunological protection against delta and some of the earlier ones the evidence for that is pretty strong now yeah because of this massive polyclonal response so so so delta's probably the best thing that could have happened to the human uh omicron is probably the best thing that could have happened yeah for the human race i i that's my thought uh i'm not saying it's the best thing but it's certainly i think a good thing yeah yeah yeah sure it's the least bad thing that could have happened yeah as i said earlier i think it's it's the transit zone into seasonal we're going to have seasonal garona in a more pronounced way i think than we did yeah and uh they're clever uh vaccine companies are already producing combined flu and corona virus excellent yeah well i've actually been telling people on on videos that uh this is probably a natural form of immunity and it's the best thing that could have happened compared to del sol i'm relieved to see that you at least uh partially agree with me which is quite well i think there are a few people in hospital that may not agree with us but but then you know you look you look at the amount in the community certainly here and you look at the hospitalization and the people who get into intensive care and die um it's so much different to what it was the the ratio and if we could only have available early treatment yeah it would it would accelerate our move through this and save lives and don't get me started as indeed we have for bacterial infections for example exactly exactly the the bubonic plague not many people know about the bubonic pain in 1900 but that's like my my wife in the background is saying and shingles oh yeah shingles is herpes zoster virus isn't it that's right yes i asked the vaccine for that was a vaccine for that but it's also early treatment yes oh absolutely yeah the antiviral treatments and that can prevent horrible things like the the enunciating facial neuralgia and hideous exactly painful conditions excellent excellent point yeah yeah i mean not many people know there's a bubonic plague outbreak and was it was it confined to australia in 1900 no no no it was the third great pandemic it was although in 1900 came out of exactly the same part of china that uh the current uh the current um covert has come out of yeah and it came for the first time to the new worlds the america and australia we had 400 cases in 1900 and john i'll just give you one really really interesting trivia the the idea of test and isolate began with a amazing guy called ashburton thompson who was head of medicine in sydney at the time and what he did he tested every rap in darling harbour which is part of sydney and he ident when the rats started appearing to have positive he then isolated them in a rather permanent way and stopped the pandemic wow so test and treat well isolate um test and isolate yeah really begin with the pandemic and i'm amazing and of course when when bubonic or pneumonic plague arises now we can just treat it with antibiotics and that stops us exactly and and i think australia is one of the it's the only continent that does not have bubonic plague in its native uh fauna oh is that right yeah okay so so it's it's en enzo enotic in these other areas uh yeah yeah yeah you you still see it in america you still said east asia occasionally in europe yeah um the the black death appears it's yeah but it's the early treatment that stops it early treatment the early treatment analogy is you have to diagnose it yeah but yeah the antibiotics are good yeah as long as you think of it it's uh yeah but like every part of medicine you've got to think of it yeah you've got to think of it first yeah yeah robert thank you so much i know it's your side have you had breakfast yet i have oh that's okay then we're normally we're normally walking through our botanic gardens at this stage but thank you for your time thank you your wife very much for for your time as well and uh my wife and my daughter are serious followers of yours john so uh um delighted and humbled robert thank you thank you yeah so let's uh do look at the comments i'm sure there's going to be um many many very positive ones and uh well you have comments do you okay oh i get thousands yeah yeah if you look through yeah i'm just hoping everything's recorded properly because i'm not very good at this kind of thing but go on as you say i normally get my son to do everything but he's a few thousand miles away in fact he's closer to you than he is to me a lot closer great robert thank you very much and uh great pleasure really has been a pleasure and an honour really talking to you so and i've learned so much um it's just just brilliant my mind's just boggling with it i'm gonna have to go around make some notes on it or something but yeah thank you so i'll pull up you know stop recording now i think recording

Channel: Dr. John Campbell

Views: 1,012,740

Keywords: physiology, nursing, NCLEX, health, disease, biology, medicine, nurse education, medical education, pathophysiology, campbell, human biology, human body

Id: FPPnyzvO7J4

Length: 64min 41sec (3881 seconds)

Published: Sun Jan 23 2022

Reddit Comments

[u/rollem_21]

Enjoyed this, good to see them mentioning early treatment, and that boosting every 3 months by the 4th you would be probably only get 2 weeks before antibodies drop right off.

[u/leslieran1]

This is long, but excellent. Near the end he talks about the need for early treatment, and talks about the medication that he isn't allowed to mention by name (ivermectin). The first 10 minutes or so are confusing but Dr. Campbell teases out clear answers on how the immune system works naturally, and how the vaccines disrupt it. Well worth watching! This immunologist has impeccable credentials.

[u/burningbun]

Where was he 2 years back lol. Hiding in his hole afraid of losing his job if he talked? Does ut matter much now majority people already vaxed