 So it looks like it's one o'clock. I guess I will begin First off with this title slide I want to just make a point this Is going to dwell a bit on the immune system and how it works and I think I Thought about this a bit. This is a daunting topic because it's so huge but you hear a lot on the news about vaccines and I'm going to try and not repeat things you can hear or read in the newspaper And try to give you a little more Basis for understanding what's going on It's going to be a sketch. It's not going to be Semester course or year or you could make a career out of this in fact It would be a lovely career Wonderful career for anyone I'll give some examples of that but the beginning picture here it shows a CD4 activated T cell that would be a helper cell and It's hooked up with an antigen presenting cell up and My point in this slide showing that there are all these fancy molecules attached on the surface That's largely how cells talk to each other when they're in proximity. They hook up their Devices sort of like putting their hands together So they're like docking posts these molecules on the cell surface. I Thought that would be a good Mental model to keep in mind for almost everything that happens They're also Humeral Not humorous but humoral meaning Molecules that float in the serum and float from one cell to another. That's another way they talked to each other Okay, this is a slide from my last presentation on this which was on the 4th of February in 2020 I believe I Regretted one thing. I wasn't even going to mention this but I'm regretted that I mentioned this is in the Titled that China Chinese Wuhan virus and That was before people knew what to call it. It was brand new and hadn't hit Hardly anywhere except in China and then that became an ugly political Thing to say and so I regret the title but it was before it was politicized and Turned xenophobic so I Think the You want to blame someone for the emergence of this virus blame humans for living in this world Because that's where this virus came from and there's more The Baltimore classification of viruses was a big advance from about 1970 and it depends on the mechanisms of reproduction of of infection and reproduction that viruses use rather than morphology and Antigens that can be detected with antibodies that are Illuminous or that sort of thing so it was really a development of the molecular biology Discipline that Started in the 50s largely because of the explanation of how DNA works We're in group type 4 with coronavirus. It's a type 4 Virus that has a single strand RNA which is positive sense meaning it acts just like one of your ordinary messenger RNAs and Another one we're going to be talking about a little bit is adenoviruses, which are used as viral vectors and that's a type 1 virus With double-stranded DNA, although the vaccines will discuss don't have the Original adenovirus DNA in a That's been replaced, but they're using the capsid Witches can be synthesized or self-assembled from pieces that are Viral like particles as they're called That Can act like a submarine to get the torpedo to its target Okay, this is well known really co vid Viral particles they're enveloped Which is one of the problems because of the envelope. There's a few of the Structural proteins Visible basically you have the spike protein that sticks out and is accessible to the immune system and that's one reason why it's being targeted as the Or used as the target of virus Vaccines They're roughly spherical about 90 nanometers and As I said with type as with any type for Virus it's a single strand positive sense RNA that's in this little container that Has a complex hook up to target cells and releases its cargo This codes also for 16 non structural proteins and Beautifully complex and more is understood about it than was last February See I guess I'll go in here. I just liked this picture. It's I I'm sure artists Conception at least in part But it shows a relative size of an expanded cell with Virons on the surface looks kind of moldy like like an old muffin that You probably shouldn't eat like Synergies casserole Anyway, this is from the National Institute of Allergy and Infectious Diseases and they are government Supported Institute. So what they produce is public domain and As I've said before National Institutes of Health for the United States is one of the great achievements of the United States government which with good leadership and Use Proper use of its talent can achieve great things Okay steps in infection. This is really focusing on the early steps first off attachment and everybody kind of knows about that I think one of the things that We knew before as it was angiotensin two receptors angiotensin converting enzyme Receptors Which are common on endothelial cells of blood vessels which are there for common in the respiratory system because you have the vascularity of the Interface for gas exchange is so Abundant there and that is a good place for a an airborne Infectious particle to attack Something that I wasn't aware of I don't think was known generally last February, but heparin sulfate which is on every mammalian cell is Part of the Attachment Process I'll talk about that in a minute once it attaches it it penetrates it requires this Action of by Protease which means it breaks up protein This transmembrane protease serine S1 member or two and And when it get off on that too much because it'll take time there are also proteases that are in the cell and some in the Golgi process even that are Playing that play a role in this Golgi process is really a pretty important in this I just wanted to show you what heparin sulfate looks like It's I made a note to myself about it so I can find my note It's linear polysaccharide These are repeating units and they're very similar the lower one here is the Medical heparin that can be senses synthesized and Heparin Often occurs heparin sulfate anyway, it's in all mammalian cells and on cell surfaces and that tends to occur and Adjacent strands attached to cell membranes or two proteins in the extracellular matrix So it's kind of an interesting player in this And interestingly to other viruses like respiratory Sinciscial virus uses heparin sulfate as a receptor to get in the cells. So you've got that and One of the points I'm gonna make I'm just say it right now is in this is that This whole system is Very geared it's like you're being attacked by something that's been planning It's I may have misspelled it The I can't tell are you capitalizing or Heparin sulfate is this this moiety of molecules a polysaccharide type Molecule the heparin product would probably be capitalized anyway in In is quite variable. I I would have to look that up to be able to answer that With better precision. I'm sure somebody gives a range on it But they these are pretty good sized molecules So Like any polysaccharide Let's see the These next few slides just relate to the use of Heparin sulfate in by the virus to get into the cell One point I was starting to say about this is that This virus it's like an enemy that's been planning its attack and has you all figured out in this case just nature is so diverse and this happens to have done its beta testing on similar organisms and managed to jump to our species but Any cure or control of this kind of virus is gonna Require very specific Strategies of attack Drinking herbal tea and gonna do it and the eye of a newt Mixed with The breath of a version or something like this isn't gonna cut it it's going to require Really careful Strategic science so any rate the Ace inhibitor ace to inhibitor I'm sorry ace to a receptor and the heparin sulfate together Cause a shift in the spike protein and It gets cleaved I Protease into two pieces Which is part of its? And there's an area and it called the receptor binding domain which It's shifted so that the Without the heparin sulfate it can't get into the cell which has been looked at a bit Yeah, I know I was I was kind of trying to make up something said is energy It I have the newt and the breath of a virgin isn't particularly Scientific, but I was doing a money python mockery of medieval science Anyway, both these molecules are necessary and they Neuropolin is another molecule that's really very interesting and Had a note here about it. It's just it's involved in embryogenesis Guides axons it's involved in angiogenesis. It's a very common molecule in mammals, but it Potentiates the attachment and Infection by the Corona virus so I Wanted to bring it to mind for you these the S protein gets broken into two Holy peptides S1 and S2 and There's changes in confirmation that Effect how it binds As it gets taken up so this is just another cell for information another slide for information sake There is one point I want to make from this slide well to actually one is this Neuropolin is really abundant not just in the respiratory system, but also olfactory epithelium and That may just have something to do with the way people lose their sense of smell At the beginning of these infections And one of the long-term effects a few people never get their sense of smell back so far and Some have disosmia where things just don't smell right or they don't smell pleasant that's Does some permanent damage to olfactory epithelium probably Anyway, the other point I wanted to make is that you have these Various No, it's not on this slide. Maybe it was on the previous slide. I guess it was on the previous slide you have of these various Proteases that are involved some are viral derived and some are host Dependent and this slide I'm not going to dwell on those but this slide has The peptidase meaning they break that they they cleave peptides And It indicates in under origin whether it's viral or host derived and Under function where it acts and you see the ones that are acting on the spike protein in particular So this is just a reference slide and it's on that PDF that I shared and if anyone's just come in if you ask one of the others if you could Chantale, I'm sure would share the note card with you that I Put out at the beginning of this Here is something I talked about a bit in February and it was more generic there are 16 non-structural Polypeptides and four structural ones This one single About 30,000 bases. It's a single strand messenger RNA type molecule. That's in the virus It acts like it pretends to be a messenger RNA as soon as it gets into the cytosol cytoplasm it of the cell it can Start to use its Equipment to make proteins just like somebody that happens to get in your door One of the first things some of these people do is go to your fridge and look for your beer So Thank you for Attention to that Chantale about the PDF So this protein this M this RNA strand has this strange Thing and I really am curious about how this Has arisen in nature, but there's this frame shifting when it gets read it jumps it has a Jump and across this Little bridge in a way Which is called a frame shift and it ends up with this long protein or peptide that has Its own enzymatic activity It's it's kind of a super Super peptide I would say There are two peptidases in that helped mature that are viral that helped mature the Viral peptide One is from I'm not going to give the names I think they're indicated on here, but once from structural non structural protein Three and the other ones from non structural protein five but while they're in situ and this thing folds up those areas still act and The one on the non structural protein three cuts the polypeptide at three different sites and those are indicated and by the black Little triangles there the Impro Peptidase on non structural protein five cuts at 11 sites and So you end up with 16 Peptide chains and These have RNA polymerase activity, so one of the first things This thing does is Replicate its own RNA strand to make a negative strand and from that it starts to do reverse Transcription to make a Number of other shorter ones, but RNA segments and Eventually these structural proteins are made This is kind of the big view a Lot of this takes place it gets down to the endoplasmic reticulum and It has felt to take place on ribosomes attached, you know mammalian ribosomes Outside the mitochondria the mitochondria have ribosomes of its somewhat different size a little bit smaller may be a little bit reflective of bacterial origin of mitochondria, but The mitochondria that has a 30 and a 55 s unit that the rough endoplasmic reticulum has these attached ribosomes so they they act and play where they're attached and the One interesting point about the endoplasmic reticulum is that it has a lumen As a lumen things go on inside of it and it the lumen has a little bit of a different environment from the rest of the cytosol And it connects or things can be transported to the Golgi apparatus. That's shown as distinct here in this diagram Golgi apparatus is involved in packaging and creating vessels and that's particularly active in secreting cells like Parathyroid or thyroid endocrine cells But in this case it packages up the Final product of the virons that get released So that's how the that's how the infection takes place. I Don't want to dwell on it so much as then to switch to how does a vaccine work? I want to go back and talk for a moment about the reproduction number Or the are not is the initial reproduction number, but the reproduction number of the Virus can be changed The example here. This is from a February 2020 slide was measles was horrific genocidal virus for Native Americans and you look in that it got a Population that is naive immunologic immunologically naive to a new antigen Then one person can infect 16 or 18 other people Easily and If you look at the formula for Basic reproduction number you have this transmission transmissibility the Factor these are all multiplicative factors proportionalities average rate of contact between Suscepted and infected individuals and the duration of infectiousness how long people are infected The transmissibility can be altered and any One have an idea how it can be altered transmissibility by can be altered by Keeping away from people It can be altered by wearing a mask If everyone wears a mask 85% of the infections are Probably not going to happen. That's the number that's usually bantied about It's in other words transmissibility is is really dependent on a lot of conditions And the rate of contact you can you can vary that you can keep infected people away from uninfected people or susceptible people social isolation, there's a lot we can do that we're not doing and basically You have a society. It's torn apart by Politics and stupidity and having an enemy it's come and you could have folded it On the ocean or before it got there or you can fight it in your coastal towns or you can fight it in Chicago or Mets or a Stuttgart or you know Milan or we're you know once it gets well inland if You just ignore it and say it'll just disappear Because it ain't gonna do that it ain't gonna do what you want to do or wanted to do and You've got to you know play ball with reality so I Like the word Argo. I like words and so I made this slide And this is sort of a reference slide That you can go back and look at in the PDF as well if you like There is so much lingo or Jargon or inside knowledge inside Language in Immunology that you can start to look at it and think what the hell but If you take these words and kind of try to Even just take this slide and just look them up one by one if I've been more I Probably would have done it if I'd had more time I could have made on my PDF so that each Of these entries was a link to a definition, but I didn't do that, but you can do that for yourself a Lot of terms you'll hear viral vector when you have Viruses as a little bit more traditional that are put into As a vaccine or that are put into a viral capsule that's a viral vector Lipid nanoparticle is what's being used with this new m RNA technology where mRNA That's related to the original infectious agents being used as your bullet to Stimulate or to give the alert to target cells and Colonial selection is a word that comes up in terms of when you get T cells or V cells that are sitting around Waiting for something to happen and then they get the signal Something's up. They undergo clonal selection. There's all these steps and incredible control in that Efficacy versus effectiveness generally effectiveness relates to real world Where's efficacies if you have a real controlled situation that you can do I Can their Reports of efficacy of these vaccines They're talking about in their group of the people that received the real deal versus the ones that received the placebo or the Non-vaccine And I'm kind of pausing in one case an AstraZeneca in the first shot. They gave a Meningococcal meningitis vaccine Because it often causes reactions so that people would think man. They gave me something. I bet it was the real deal So that people's perception of what was happening would not affect their outcomes of their study, but at any rate Studies talk about efficacy, but the effectiveness is sort of yet to be proven That's how it's going to work in the real world In the United States the effectiveness is about like everything else has been recently Not so hot, but there is hope Adaptive immunity is the term for what keeps you alive. What keeps you from rotting From the moment you're exposed to the air You also have innate immunity and I have that in the lower rate and corner anagen recognition signal transduction that's basically cells Get turned on by Encounter and they send out their signals in various ways, especially cytokines and such And this human leukocyte anagen HOA system is really important. I want to just Talk about that for a second and then we're going to go on There that's That's a system of genes and if you do transplantation or Cancer stem cell therapy You've got to do matching of HLA genes or else you'll get rejection of the of the cells that are Whether it's transplant or stem cells that are introduced these MHC or major hystocompatibility genes or molecules I Hear the terms used almost identically. I Like to specify if I'm talking about the genes or the molecules all those genes are on the short arm of chromosome six These are not the same as blood type You know people Sam type a you know that that's For blood typing for like blood banks. That's basically Chromosome nine stuff so that's a whole different thing, but at any rate There's really three classes of MHC molecules. There's over 200 of genes associated with these and I'll just I just have them listed there. I won't read them the They are very important to professional antigen presenting cells, which I'm going to tell you about So I'm saying all these things because I'm gonna you're gonna hear it again and some of the description and particular importance this plasma cell Leading to factor cells that Factor plasma cells that produce antibodies or memory cells and you can have the same with T cells thymus process. They're all Basically blood cells that Generated by stem cells in the bone marrow, but the T cells get processed by the thymus early on and Somebody's telling me to move on So anyway Also cytokines are extremely important. They're soluble hormonal like short distance for the most part molecules that Are part of the communication system for cells Interleukins are an example that that's There are Interferons interleukin's chemokines mesenchymal growth factors tumor necrosis factor Adipokines over a hundred genes coding for different cytokines. They're very important You hear about cytokines storm. Well It's a big subject Big important thing here. I want to put in your head CD4 T helper cells CD4 versus CD8 The These are the actors in the system the antigen presenting cells include in the Middle top row macrophage the left middle row B cells and dendritic cells the dendritic cells back when I think I talked about the liver and Hepatose Hepatitis non non-alcoholic Steyato hepatitis fatty liver disease from Which was sort of a metabolic disorder not from alcoholism or infection, but you have these and Dendritic cells that were initially discovered by Langerhans. He thought they were nerve cells and Those take up Antigens and Process them and then post them on Specific types of molecules on their surface I did I Through the slide in because I'm going to talk about vaccines in a couple minutes and it just lists Another sort of reference slide in the lower left-hand corner it lists Various Strategies for vaccines an activated vaccine, which is what I think Is being tried in India? Live attenuated vaccine, which I think is what's going on in China and I Replicating viral vaccination vector vaccine, which is Like our mRNA technology and non replicating viral vector vaccine well that that means It gets a little confusing because like the Russians are using Add a human adenovirus type 5 and 26 Which is non replicating but they're putting Reverse engineered DNA that will produce mRNA that will produce spike protein components that will then get chewed up inside the cell and Put through the lumen of Goes through the tap pour or the tap conduit which is a large protein That controls what gets into the lumen of the endoplasmic reticulum and gets processed there and posted on MH1 or MH2 major histocompatibility molecules MHC1 and MHC2 and Pieces of antigen get posted on Those and if they happen to come from you when your T cells come up. They say okay. We know this guy. He's all right and If they're strangers then your T cell says I Want you to step over here and keep your hands up So anyway There's a lot of strategies that have been used this mRNA technology is the new thing Most people think of this in terms of what the goal is Producing antibodies, but it's really more complex than this. There's five different types of antibodies that mostly in terms of dealing with Vaccination you're you're talking initially you produce IGM antibodies which are sort of like this they have Two long chains and two short chains or like heavy and light chains that are Y shaped If you took about I don't know five or six of these put them on a pinwheel like a martial arts weapon Then you'll have an M at the bottom M immunoglobulin Now the because the antigen binding sites on such a a pinwheel type Antibody would be so multiple you get a glutination which helps an early infection so that antigens get clumped and phagocytate Macrophages can come up and eat them and process them and put some of their antigen derived protein on their MH2 cells and Wake up the T cells and get them stimulated and they Go through some changes. I'm going to tell you about in a second. So at any rate IGM and IGG IGG is the more permanent or longer lasting or the secondary wave of antibodies that are produced and systemic infections or serious infections I Don't want to get into the other ones Here because I won't get done. I couldn't find a slide. I really liked that showed a couple points So I drew it my own I forgot here You have two cells here a B cell and Did I speak poorly? Thank you, I may have gotten twisted in my sense Not sure anyway The B cell is on the left and here's a T cell on the right and this T cell has a T cell receptor that's specific for this B cell and The B cell has Antibodies on its surface and if an antigen comes up that Attaches to it it will take it inside. I've got another slide that shows that but I tried to indicate here was sort of getting Scooped in or sucked in and it gets processed in a vacuole with proteases and ends up going through the tap Transporter that controls what gets into the endoplasmic reticulum and gets processed in there and pieces of that antigen end up getting put out on to the MH2 Molecule these there is these MH. I'm sorry MHC to class 2. I should say There's two of these that are important In this in terms of cell biology MHC class 3 and includes soluble components like complement system and that sort of thing but Again these are all from the chromosome 6 short arm The B cell is a good example I hit it there of one of the three the dendritic and the macrophages and the B cells are the antigen presenting Cells in the immune system. That's a really important concept and they all have these MHC Class 2 molecules They will hook up with seed with T helper cells that are specific These these are Brothers by a different mother So to speak This T helper cell is specific for this B cell and they stimulate each other and There's one other thing it has to be a CD for molecule has to be on this The Let's see Kind of forgetting. I made some notes to myself. Don't want to say Well, anyway as CD4 is a cluster differentiation for The two to remember cluster of differentiation is a good Translation for CD4 if you just remember CD. That's fine. I'm going to tell you about what CD4 does The CD4 molecule is required for the T helper cell to get turned on if It Interacts with this antigen Major histocompatibility molecule to MHC to That's on the B cell Then it will get stimulated It will release cytokines into the environment which among other things it'll it'll tell other cells in the environment that this this We got something going on here and I've got a cat that's sitting on my notes now. So I'm on my own This cytokines will interact with the B cell and It flips its switch the B cell proliferates to form a clone and It differentiates and forms two kinds of cells mostly effector plasma cells which Effector cells are cells that are carrying out defense mechanisms the effector plasma cells Are producing antibodies and then there are some memory cells that are There they have longer Half-lives and by quite a lot and they will reactivate when This infection ever comes back assuming you win and eliminated Here is a Somatic cell every somatic cell except for your red blood cells which has your red blood cells have no nucleus Basically, it's usually said every nucleated cell has mhc MHC one class MHC class one Molecules on them in this case. I made an Antigen that happened to get in there Some kind of invasions invasive thing like a little virus that's I made it as a red star And then one of the arms of that star ended up on the MHC Class one molecule if a T cytotoxic T cell that's a CD8 CD8 and CD4 are cofactors They these These interactions are very controlled so the immune system doesn't go crazy But if the cytotoxic cell comes up and Sees that There's this and it's a specific T cell again for this particular Molecule And it sees there's this antigen and says this guy didn't belong here And it has CD4 CD8 has to be there to interact with the MHC one molecule just like CD4 Is an adjacent molecule to the T cell receptor and the help helper cells it interacts with like down on the neck of the of the MHC won't class one molecule Then the T cytotoxic cell turns on it releases cytokines and it can also release particles that have enzymes one perforin will drill holes basically through the membrane of the somatic cell and then Granzymes are like Toxic will kill the cell This is one way your body controls cancer This is a an effective way for something like cancer your Cytotoxic T cells are needed now. I had one thing I was Confused at one time about AIDS and why people with AIDS were getting This carpose sarco the sarcoma Cropose sarcoma is Presents on the skin and it's pretty rare But it's actually not due to this CD8 system. It's due to the CD4 the AIDS kills the CD4 helper cells Which is probably the most important single cell in your immune system and There is a Type of herpes called herpes type 8. There are nine types of herpes simplex virus and that infect humans that are know of and that type 8 is Normally not Doesn't cause severe disease, but if the T helper cells are are down then it builds up and proliferates and causes Immunogenic effects and you get this carpose sarcoma. So In that case, it's it's a sarcoma that's arising or a malignancy arising from defect in the T4 CD4 T helper cells. So any rate B cells and T helper cells have to be brothers They have to be kind of related and recognize the same epitode or active little area of domain of a of a Polymer of amino acids or a peptide or an antigen and Over on the right I showed this because I thought it showed a nice way of how the B cell how the the antibody picks up an antigen gets engulfed Processed and then pieces of the antigen present on the this would be a B cell I guess so that's that would be a a And MHC to Molecule and then a T helper cell which has a CD4 Molecule will interact with the B cell and say yeah, this doesn't belong here We need to gear you up and wipe this thing out before it wipes us out. So that B cell undergoes Proliferation differentiation and produces Effector cells that make lots of antibodies. That's what you want a vaccine to do Okay Clinical testing now just say quickly number one thing safety number two efficacy and we had some discussion in Science Friday at this yesterday of that You know it it'd be Unconscionable to give a vaccine to millions of people that Would make a lot of otherwise healthy people sick the vaccine has to be tolerable You wanted to do what it does without causing any extra effects as much as possible So You do preclinical study was Mice with animals you test for tolerance toxicity get some idea about How much the drug might be tolerable per mass body mass and If antibodies are formed that sort of thing then you do phase one these are all done as separate studies These are not combined or pooled numbers and then you do phase one studies and that's usually I Took this from I Guess the FDA, but most of the time when I hear people talk about they say a hundred patients or so You want healthy people there? You don't want to you want to see what's going on without having comorbidities Confused or muddy the water? Phase two you you it's a bigger study yet, but you also want maybe a hundred to a thousand people and you have termination of dosage in phase one and two you fine-tune it in phase two and then find phase three is thousands of people and One of the problems is a lot of countries are Bypassing phase three or not doing Convincing phase three studies with sufficient follow-up and so That has hurt their credibility in terms of the vaccines they're producing This is a wonderful story and I give the reference here it's and I'm not going to tell the story But this is a lady came from Hungary Kariko from Hungary around 1985 and She was at first at Temple University in Philadelphia and then came over to University of Pennsylvania and I did not know her I was at University of Pennsylvania at that time But it's a big place with lots and thousands of people thousands of people doing research So She was Sidelined and sort of dismissed but she was interested in M RNA technology and the other Forms of immunization were so well established that people didn't want to fund her and she connected with Drew Weissman at PIN and eventually I Staying with it Got somewhere with it. She's vice president of I Guess bio bio-intect Which I guess works with Pfizer Nano carriers, I'll just say this is a reference slide the nano carriers a lipid Biparticle that contains a virus and that's what the M RNA technology is using It takes the RNA for the spike protein and takes pieces of that and so it has antigens that can be Presented to cells and it's given as a As a shot in the arm and the deltoid muscle and We'll get into some somatic cells the little lipid nanoparticle will merge with the cell membrane or It may encounter some antigen processing cells and with the second shot There are probably going to be more antigen processing cells in that area drawn in by Whatever immune inflammatory response is generated initially, but This has an international non-proprietary name As listed Usually almost unpronounceable But it was the first to get authorized for emergency use That is a good question The Fact is Shiloh asks which vaccine producers best I Think they're both quite good. They both have similar efficacy as I'm gonna talk about But the truth of it is that right now if you've got a shot at getting a vaccine you get what you get as Especially true for other countries Because there's there's not much there's no choice unless Yeah, I guess you're in the White House or something. I guess you can get whatever you want, but The Pfizer trials has 40,000 plus participants 95% if effectiveness in other words If you had a Control group unvaccinated group that had a hundred People get sick with co vid theoretically Only five of them would have gotten gotten sick if they had had the vaccine that's what the 95% means It's two shots intramuscular 21 days apart ages 16 and up this does have a fair response but both Moderna which does mRNA technology and Pfizer have a fairly big response and they're recommending the people that work in the Doing surgery or working in the merchants room or whatever if they get the shot they need a few days to get past Blue like symptoms and there's a fairly high number of those kind achiness and malaise and some nausea and They've not had any terrible responses to it in the development of the Moderna vaccine they had questions with Transverse myelitis or that's where Like you got inflammation across the spine the spinal cord Which is really scary, but I don't think those were felt to be related The Pfizer's for 16 years old and up and I just threw these in for fun This was the first lady to get this Vaccine a UK grandmother the first one in the UK anyway, I think she was the first one ever To get it as a patient. She was 91 years old said it was an early birthday present and Pfizer is really gearing up quickly to produce more of these and Here's William Shakespeare He was number two to get jabbed in the UK and So I couldn't resist I threw in this slide To vaccinate or not to vaccinate There is no question All right Moderna is very similar to the Pfizer except the Pfizer needs to be like 70 degrees centigrade below Zero negative 70 degrees zero to Not to be degraded and the Moderna has much milder requirements and can be stored in freezer or refrigerator for And 30 days and has to be used within 30 days the Pfizer has vials. They're multiple dose vials. They have to be used within five days The main allergic Concern about allergy with these is This peg or polyethylene glycol or it's not like polysorbate like molecule Which is felt Might cause anaphylaxis. There were a few patients that had anaphylaxis with these injections So cold stain cold change storage means it has to stay cold or it ruins it gets it can't be refrozen It and if it gets warm It will disintegrate very quickly and have no effectiveness So this gives a review of the Conditions for Moderna and Pfizer which are quite similar. I'm pretty close to finished Moderna and Pfizer are kicking up Moderna's Trials they had a weird thing and I think they gave like 40,000 people in Brazil full dose and then a Month later full dose Pfizer's 21 days separate for the two doses in the UK. They screwed up somehow and gave a half dose on the first injection and In the UK they had about 95 percent effectiveness in Brazil it was in the 50s and so the average For Moderna was 70 percent. It's not clear what went on there and that's being studied further But even 70 percent any vaccine that has more than 50 percent It's kind of the cutoff is considered to be a Decent choice now AstraZeneca is a DNA double-stranded DNA that's in and Simeon or a champ chimpanzee had no virus as a viral vector And it codes for the S protein DNA. So it gets into the Cell And you would think it might get to the anagen presenting cells more effectively But anyway, it gets into the cell and goes through the same processes of getting chopped up and pieces of the anagen get put on those Inflammatory docking stations the MHC one class one molecule and MHC class two molecules Now Russia I'm not going to get into too much Russia has Sputnik which is also based on more traditional Therapy it is interesting. They kind of short-skirted phase three and so nobody's the WHO and Europe and Nobody anywhere else has signed off on this as being Vaccine of choice, but this disease has rendered a lot of governments absolutely desperate and The I took this Article and just quoted it. It's from in our NPR National Public Radio The thing that I wanted to point out and I put it in highlight the concern is they had not seen raw data from Sputnik trials basically they're dealing off of of News reports Which you know how that is But It's this kind of vaccine. It's more traditional It's easy and inexpensive to produce and it doesn't require super cold temperatures. So there's no cold chain So they've got a workhorse of a vaccine Now in terms of cost Moderna is not going to make a profit on this until the Pandemics over so their vaccines about four dollars a shot The advisors I've seen twenty to thirty dollars per shot. I don't know what the Sputnik would be but it would be pretty cheap but The Brazils also using the Chinese virus Chinese vaccine, but recent Data has indicated that its effectiveness is about fifty point four percent so Yeah, this is another sort of summary slide Shows what a complex system we're dealing with and My last comment on this this is going to require real specific remedies and procedures and approaches to fix this problem It's also going to require the world to grow up and become more cooperative and share information and You know Maybe respect nature Stop eating anything that has fur on it and There it's a tragic thing I think that the Lack the Alacrity is cheerful promness, but there's been an absolutely no alacrity in the dealing with This Pandemic and it's allowed it to disseminate around the world and the more it goes the more chance it has to Mutate it had a and an SNL a form in variants in China and then in Italy another variant emerged Sometime over the summer and then more recently South Africa and particularly the UK and had variants that have more infectiveness in fact the increased infectiveness can be anything from a difference in the way the Confirmation of the spike protein is to Possibly more infectious particles being coughed out because of something in the path of physiology Being a little different, but in any case We're only a few mutations away from something that could wipe out out 95% of the population in my opinion. I don't want to scare you but people need to stop screwing around and The more time you give it the more time this thing has to spread everywhere and Imagine if these were enemy troops They're now in every town Controlling every highway controlling the restaurants everything Should have been stopped before they got into the border, but That sounds xenophobic or something, but I mean this is a model for What we're dealing with here because you can't see it you've got People idiotically denying it it Requires intelligent moderate Civilized governance People that leadership that is proactive and visionary and not just Lying So that's completes everything. I think I can say right here. I Can talk more about details next week Any questions although sometimes the host Probably feels like just kill me It's horrific what this does to people and The I don't think we're winning yet That's that's I'm glad you asked to brought that up. I meant to say then are we winning yet? Sorry. No And that's on us We're gonna have to do better interestingly Ebola the vaccine for Ebola required A cold chain And we did pretty well with it and It seemed a lot more scary than this because it caused this hemorrhagic Disease that just knocked people off Overnight practically and I hope I didn't confuse people too much way I wanted to show you the breadth and depth of the Immunology which this is all dependent on the immunology and molecular biology. I Took you in about up to your ankles What's your nose doing down by your ankles there synergy? I probably missed lots of questions. I'm kind of get Rolling Yeah, that's the Cleveland Browns are one of the things that We've lost We've lost so many people there It's a dark sad time people dying Alone no goodbyes it's Hard to understand how people in leadership positions could allow themselves to Let this go That's a good question Phil. I think that because of it's a zoonosis there there's even a recent report of Family of gorillas in San Diego who are infected with COVID They've been coughing and it's going to be in all these animals. It's in cats some dogs It's you know humans are not that special There I hope the gorilla family survive it They're so similar to us genetically that they could be in danger But It it's it's probably going to be around forever we need to have cooperation on a global scale so that It's like a global immunological task force that we can Have heads up of potential viral infections and ways of dealing with them that before they wipe us out I was impressed that on I heard a man with Irish Brogue yesterday on Science Friday mentioned he looks forward to the day when The Vaccines and health Responses are up and running before the pandemic hits we're supposedly smart enough to do that but Humans have a way of sabotaging themselves. So well, Dr. Mike Ryan I'm not sure I don't know Thank you Mike. Thanks synergy Vitamin D is fine. Don't take it till you're toxic, but it's probably a good idea Helps prevent prostate problems for one thing I Appreciate your attendance This is My son's birthday was yesterday and that he died four years ago. So And I always feel down about this time of year But imagine how torn up so many people are Family members suddenly gone all around the world. This is a Savage virus. Oh That's really a good point Baragon MRNA does not change your DNA It does not work in the nucleus. It doesn't go in the nucleus. It doesn't it's not part of that scene now the Viral vectors involving adenovirus whether they're chimpanzee or Human like the type 5 and type 26 the Russian virus has Those will be transported to the nuclear membrane which is a double layer membrane and has nuclear pores Which are have a protein? Complex that controls what gets in and out and that's where the adenovirus injects DNA into the nucleus in most models and so the DNA does get in the nucleus because it needs to be transcribed But And that's where that takes place And then mRNA is produced and it comes out into the cytosol where they aren't where the ribosomes are and gets translated but even with that the DNA is not expected to have any impact on your genome Let's see wouldn't have a vaccine be somewhat effective I Think if we had antivirals, I'm not sure if this answers your question. Oh half dose if This is a good question if the Vaccination program is not done wholeheartedly. It may allow in my opinion for escape of By Variants that can Survive it Now they say it's not a problem that When these variants become an issue, they will be able to modify the vaccine but take a look at all we know about industrial engineering and manufacturing producing things and distributing them and How difficult it is to get this vaccine up and running and Distributed and then have people take it So It's you know, you you it's like you got one job, you know, you got to do it, right? You got one shot You got one bullet in your gun and About five seconds to use it or you're dead It think of it in those kinds of scenarios I don't think there's much room to screw around here and I Think that the people spreading disinformation and It's it's They're very harmful I'll just say they're very harmful Wonder how they sleep at night, but thank you synergy. Yeah, and the people relating it to What is it g5? What is the? Cell phone thing This new generation of 5g My phone my cell phone is dyslexic, you know somehow the Injection is going to make it so that Bill Gates can track you Yeah, I think Bill Gates doesn't have that much time in the day Well, I can think of a lot of a lot of people I'd rather not have tracked me I would settle for Bill Gates. I don't bring it on Bill What's he gonna do hit you with the You know a noodle or something. I don't know the blue screen of death. Yes, he will He'll steal your precious bodily fluids. I know they're these are Siri that's an interesting point that people Claiming expressing their fears so readily this way and that would make Maybe something plausible for a one-hour made for TV movie or sci-fi short story or something, but You know if you know much about medical physiology and I know how difficult it would be to cause sterility in a Systematic way Thank You day Appreciate your attendance. Yes. That was a doctor strange love reference Phil So But we're down to 24 minutes after I probably should wrap it up Thank you all very much again. It was an honor to present to you. Oh and next week we have once again a Panel to discuss some of these issues further