Thank you. Until now I couldn't find a video like yours. Out there there is nothing but short 4-6 minute videos with little explanation as to the bio-mechanics. Instead you satisfied my curiosity, Great job.
This is probably one of the most informative yet easy-to-follow lectures I've seen on this topic. Thank you for taking the time in creating and sharing this video! :)
Hi! Just wanted to come back to let you know that I just received the vaccine. This video helped me understand the process. Thank you and stay safe everyone!
Many thanks for the excellent and informative lecture. I would love to see specific findings about a possible cytokine storm resulting upon exposure to Covid-19 or any corona virus post innoculation. I would also be very interested to know the exact contents of the mRNA vaccine and the medium on which the S proteins are cultured. It matters tremendously in terms of the safety profile and possible long-term or later term side effects that could present years or decades later. Your presentation is much appreciated. Many thanks.
Great explanation. Just wondering if we know for sure how quickly the S protein is expressed & recognised by the memory cytotoxic T cells before the release of the new virus particles from the cell? Also would be interesting to know how the lipid nano particle actually gets into the cell. Just diffuses across? Many thanks
If you search for liposomes, that should give you an idea. It’s many years since I studied this stuff but I believe it’s a bit like exocytosis, but in reverse (and not just endocytosis cos that seems to form a vesicle as the material enters the cell through the membrane, rather than the lipid package already existing in the extra cellular space).
If I’m not mistaken this “lipid nanoparticle” described in the video is for all intents and purposes is a virus. A virus that is used to shuttle genetic material across cell membranes and get mRNA into your cell. Here’s where a lot can go wrong. Free floating rna in you cell could theoretically recombine with other strands of rna and be taken up by another virus which could then infect you. And this technique could also lead autoimmune disorders.
What's to keep these spike proteins from bonding to cardiac muscle cells and then having killer T cells from attacking the infected heart muscle cells? Or any other vital organ cells? If the muscle cells start producing these spike proteins and then bonding to other muscle cells which the killer T cells destroy, wouldn't one lose a whole lot of muscle mass? What if a person's cells produce these spike proteins at a faster rate than the body can kill? What shuts off the mRNA? Will a person continue to produce these spike proteins forever? Won't the artificial mRNA continue to replicate itself?
It can not. Because the vaccine can not self-replicate. It will infect few skeletal muscle cells, leading to their destruction by cytotoxic cells and thus vaccine (mRNA) too will be lost. Thats it.
@@MedicoVisual But what would happen if just one infected cell remained or was not killed off fast enough? Would the artificial mRNA replicate? Thank you for answering these questions. I like to be informed before I have something injected into my body, and the news media seems to say just take it or you're killing grandma. This vaccine scares me because it hasn't been a year since even this video. I don't think researchers have any evidence of long term side effects. This video said human trials would take a few years. I know people are desperate, but should we throw caution to the wind?
@@nb4749 There is no artificial mRNA. mRNA is simply the sequence of nucleotides, and same "nucleotides" are used in synthesizing the vaccine as those present in nature. If the infected cells are killed a bit longer, the person vaccinized will have redness and pain in deltoid [shoulder] muscle for a day or two, followed by recovery.
@@nb4749 Your concern regarding the safety is justified. But in real world, nothing is really "Safe". Every drug or medical procedure may incur some adverse effects in very few people. However, the potential benefits must outweight the the potential risks for a drug/vaccine to be advised. Compare the deaths and complications associated with COVID-19 to this vaccine. Despite of rigorous testing for 10 months in thousands of people, there were no severe adverse effects. It means the adverse effects may be very very rare. Even, theoratically, I can't think of any potential severe adverse effects. I would take this jab as soon as it becomes available in my area and will share the footage here if they allowed me to do so.
Excellent Question. I could not find a very specific answer to this from Moderna's and Pfizer's docs. Their visuals and infographics depict the target to be the muscle cell, and hence I had depicted it the same way in this video. If you come up with a clear-cut answer, please share with me too.
@@MedicoVisual I understand that, part of the technology of mRNA vaccines carried by lipid nanoparticles, allows to generate specificity in the union with the target cells, through the technique of incorporating or "doping" the membrane of the nanoparticle with polypeptides that represent the exodomain of a virus natural that could couple to the receptors of the target cells to infect them. what I do not know is whether the mRNA vaccines currently in progress use this technique.
Excellent overview. Do you feel we must hit a sweet spot with the dose? In other words too much mRNA entering too many host cells will trigger an innate immune response that is too aggressive. Dose dependent autoimmune reaction against the cells infected with the mRNA by the CD8 T cells thereby damaging a critical level of host tissue. Essentially causing a transient autoimmune disease.
How efficient is the lipid nanoparticle in getting absorbed by the muscle cell? And once it is absorbed by the cell does the RNA always make the cell express the proteins it is encoded for or could it be possible that the cell might ignore the RNA that is present and continue to behave normally? The reason I ask is that people say one of the unknowns about mRNA vaccines in general is how efficient they actually are and how many doses might be necessary. I'm wondering if that is an issue with this covid vaccine in particular. Thanks for such a great video with an awesome explanation!
Great points. As per my knowldge there is no such study that evaluated these things. Phase 3 trials of this vaccine are starting and that will reveal the efficacy of this vaccine.
Good question. Just wondering about the M OR Renée once it arrives in the sale. Could it be damaged in transit & then start coding for an entirely different protein that nobody was expecting? or are there are checks & balances along the way?
I came to this video after the end-phase trial of Pfizer and Moderna mRNA vaccines and the immature approval of poor countries for Sinopharm and Sinovac traditional vaccine trying to figure out why the first ones are more effective, and indeed more expensive. Thank you for simple, and clear explanation.
MedicoVisual - Visual Medical Lectures www.google.com/amp/s/www.livescience.com/amp/coronavirus-vaccine-trial-no-animal-testing.html I meant to say the pre-clinical trials were skipped.
18:26 question: I am wondering if another reason why mRNA vaccine could be better than antigen vaccine can be that eliciting MHC1 in the first place, could deliver more effective and clear cytokines messages in comparison to immune system, mainly via MHCII reactions, having to locate antigen spike proteins floating around plasma. what do you reckon of that, dear Doctors ? Besides, could MHC 1 system also elicit interferon gamma and interferon alpha thus respectively downgrading aggressive Th17 immune response and reducing initial infection load? I hope my question makes a sense.
I am a mechanical engineer and have little to no detailed knowledge of the human immune system beyond the layperson. This video was an excellent explanation of how a synthetic mRNA vaccine actually works compared to a traditional vaccine. I find this information both fascinating and a little bit creepy (intentionally reprogramming healthy cells with manufactured genetic material is seems like the plot of a Sci-Fi horror movie). Great job with this video!
Very nice lecture, you are doing great job and I’d say you maintain a perfect balance for being “scientific enough” for non scientists. Keep publishing new videos!
Seems like some kind of #Windows update with no patches possible in case of a problem? I want a #Firewall because i feel like the future is full of #TrojanHorses!
It never "produces" mRNA. Some mRNAs are dropped into the cells by lipid nanoparticle. They can not undergo self-replication. After making few spike proteins mRNA is destroyed. Cytotoxic T cells will destroy the infected muscle cells causing the redness and swelling at injection site. Within a day or two muscle will then heal.
isnt there the risk that the mechanism of the cytotoxic t cells as part of the immun reaction due the vaccine can lead to an excessive apoptosis of to much cells? especially if you have an mhc i polymorphmism- so you have got of the risk of an excessive immune response?
Good point. I think such risk may posed with a self-replicating vaccine. I don't think a therapeutic dose of this non-self-replicating mRNA vaccine can lead to such problem. However, I can't say it for sure. That's why clinical trials are there to assess such adverse effects.
My question exactly. Previous attempts to create a vaccine for the SARS virus had catastrophic results when lab animals were exposed to "a" (as in any) corona virus post innoculation. I am not clear as to the platform used for those vaccine development attempts. I am very opposed to skipping animal trials for any vaccine or pharma product.
Is it possible after assembly of virion the spike protein fragment goes to cell surface and bind to MHC1.... How it is possible?? Need your kind response.... Thank you
This is one of the best videos of immunology explained in non-medical language. I am not from a medical background but still, I understood the concepts very clearly. Thank you for your wonderful videos. I have a request. Can you make a video on the HIV lifecycle and what are the obstacles to finding a vaccine or a cure for it? Now we have a better understanding of these viruses but still no solution coming up.
Thank you so much for your appreciation. Right now I am making a visual lecture series on hepatitis B virus. I will make a video on HIV soon. Thanks again.
Very educational and detailed video! I have a question though. I read the following comment on TH-cam and I was wondering if you could comment on it, whether it's true or not that in the Moderna vaccine (unlike Comirnaty) the CD8 T cells won't be activated? "The Moderna mRNA vaccine has a transmembrane anchor so the spike protein will be embedded in the muscle cell plasma membrane and will tag the cell to be degraded by a macrophage via the exogenous/extracellular antigen presenting pathway. The exogenous antigen presenting pathway leads to the antigen (a piece of the spike protein in this case) being presented on Class II MHC and not on Class I MHC on these macrophages. As a result, you get CD4 Helper T cell activation and not CD8 Cytotoxic T cell activation."
thanks for the appreciation. Well, I don't think that information being presented in this comment is correct unless it is backed by a peer-reviewed research article. As the Moderna's vaccine infects the muscle cell, spike proteins will be processed by proteosomes and will be presented on MHC1. So cytotoxic cells will be activated.
@@MedicoVisual Thanks. I have found this product and an interresting resource. Thanks for the videos. organixinc.com/lipids/mc2-dlin-mc2-dma-tbfb8 www.ncbi.nlm.nih.gov/pmc/articles/PMC6383180/
how widespread is cytotoxic CD8 response against (muscle) cells expressing S-protein? How many cells are expected to express the S-protein after vaccination? Is it just local or systemic expression?
Thank you for putting this video together. With mRNA vaccines being so new, I hadn't yet seen a visual explanation as to how they work. This is the EXACT type of video I was looking for. Also, despite my not working in the medical/healthcare field, I was still able to completely understand all of the concepts outlined in your video. If this vaccine were to get FDA approval and is effective against COVID-19, I would be very excited at the prospect of mRNA vaccine technology being applied to other viral diseases!
Thank you for you explanation. I just got the Pfizer BioNTech Vaccin and really wanted to understand what was happening in my body. I can confidently say now that, at least on a basic level, I do. So thank you for your work!
So I read in phase II data that some developed binding antibody (to the cell expressing the antigen) and some developed neutralizing antibodies to the virus itself. Couldn’t the former cause an autoimmune reaction?
No, it's not like that. Antibodies are usually produced against different parts of several different proteins of coronavirus. An ideal antibody should not just "Bind" with the antigen (viral protein), but also prevent it from causing any damage to the host (human). That means this antibody should not only "just" bind but also "Neutralize" the harmful effect of the virus. SuNeutralizingody is called the "Neutralzing antibody." For example, an ideal antibody against the Spike protein of coronavirus should bind with the spike and prevent it from attaching with the ACE2 receptors in the human lungs. Sometimes, the antibody may just "bind" with the Spike protein (or any other antigen of the virus), but DO NOT prevent (neutralize) it's the harmful effects i.e., It binds but does not prevent the spike from attaching ACE2 receptors. This antibody is NOT "Neutralizing antibody"; it is just a "Binding antibody." Remember, a "Neutralizing antibody" is also a "binding antibody." But the Binding antibody may not always be neutralizing. Finally, if the body produces an antibody that does not even bind to any part of the virus, it is neither a neutralizing antibody nor a binding antibody. (It is just a redundant antibody.) So the best antibody or the ultimate goal of a vaccine is to produce the highest quantity of "Neutralizing Antibodies," but "Binding Antibodies" do help to some extent and thus are desirable as well. For example, they can bind with the virus, thus tagging it as a dangerous substance, so the immune system may quickly destroy it even before it can cause harm.
That's a very good explanation. A doubt. As it is a RNA virus, which has tendency to mutate over time. Will this vaccine still be effective against this virus?
Thanks for your appreciation. We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important. BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely. 🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/) P.S: I am not an expert in this field. Any insight into this by an expert would be highly appreciated. Thank you
Is this also the body's natural response to exposure of a virus? If this is the immune response to the introduction of mRNA, how does it differ from the naturally occurring response when directly exposed to the virus? For example, if someone is exposed to the virus, is infected, and then successfully fights it and recovers; isn't the end result the same as exposure to mRNA vaccine? Are CD8, B Lymphocyte, and CD4 cells not produced in the same way? I guess I don't understand how an mRNA vaccine is more effective at fighting future infections than the body's natural response after the body has been exposed, naturally develops an immune response, and then in exposed again in the future.
Yes, you are right. Natural response is pretty much the same. I don't think vaccine is more effective than the natural immunity. They only reason I can think of id that in case of vaccine, 2 doses are given. The second (booster) dose may thus improve the immunity formed by 1st dose. Other than that theoratically, a single dose of vaccine and natural immunity should be equally effective.
By rule, MHC II is used to present the protein fragments only by "Professional" Antigen Presenting cells e.g. Macrophages. Other cells can only use MHC I. Its an established fact in immunology. Don't know the exact reason though.
Great work - Thanks heaps for this video. I was wondering how long this whole process takes? From the vaccine entering your body to when the mRNA infected cells are destroyed. Minutes, hours or days? Would love a timeline.
@@MedicoVisual Ok I just watched your Transverse myelitis video and in there it's exactly what I mean. What if (I am not saying it is true), but due to vaccine the body might start attacking it's own cells or whatever which have a similar spike protein? Exactly what we saw in transverse Myelitis video.
@@MultiSciGeek well, theoratically it can happen. But in reality, it is very unlikely. Let me tell you why: 1. If spike protein resembled some important bodily protein, there would have been a whole lot of cases of autoimmune diseases caused by natural COVID-19 infection by now. But despite of literally millions of people infected with COVID-19 there are little to no cases of autoimmune diseases followed by disease (there are some cases out there but it is not statistically significant to consider that they are caused by Sars-CoV-2 and precisely by "spike" protein of spike protein) 2. Moderna and Pfizer had enrolled more than 30000 participants in their clinical trials yet no one experienced such illness. 3. Although there were few cases of neurological illness with Oxford's vaccine. It is less likely due the spike protein. Oxford's vaccine uses Chimpanzae's Adenovirus that has its own protein receptors. That may be the culprit rather than spike protein. Furthermore, they haven't revealed that the ilness was due to vaccine or not. (Personally, I think Moderna's and Pfizer's vaccine should be much safer than Oxford's and even CanSino's vaccine due to a single antigen i.e Spike protein only). Please note that I am not against Oxford's vaccine but I won't trust it unless it gets approved by FDA or they reveal the data to the public.
Sir I have some doubt ... surface spike protein are continuously changes so our specific immune response does not recognise .. This mRNA 1273 vaccine generate stable spike protein then only single specific spike protein antibodies made .. how infection is prevented 😃
I had a similar question. What happens if there is mutation in the virus which changes the spike protein slightly? Wouldn't that mean the antibodies produced from this vaccine would no longer bind to this mutated virus? This is basically the influenza situation with antigenic drift but maybe coronaviruses are more stable. Do we know how stable has the spike protein been as this virus has spread worldwide?
@@Free-g8r That's a great question. We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important. BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely. 🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/) P.S: I am not an expert of this field. Any insight into this by an expert would be highly appreciated. Thank you
I didn't understand why, when the mrna is injected it can not cause the disease ? How does mrna enter the cell althought it has no spike protein which binds to the ACE2 ?
@@MedicoVisual 1)Although coronavirus can replicate its self, why mRNA is not self-replicating ? 2)In which part of the cell you drop the mRNA, nucleus? cytoplsme ? Thank you for your answer.
@@zehravigna4873 1. Simply because they have removed the "Replicase" enzyme's part from RNA, only spike protein's part is present 2. Its dropped in cytoplasm
@@MedicoVisual You say that it is dropped in cytoplasm. But when the doctor is applying the vaccine on the arm (or somewhere else), when he pushes the needle, how does he know that the area where he inject the vaccine is the cytoplasme and not the nucleus ?
Indeed. The excellent lecture. However, I have a question. Is the mRNA + lipid (PEG) going to enter into a specific cell or it will target randomly by entering into different cells such as heart, nerve, brain, liver, kidney or. other.
Yes, generally phase 3 clinical trials consist of 3000 participants (Ref: Basic And Clinical Pharmacology Book by Bertram G. Katzung). The fact that they enrolled 30000-50000 participants in phase 3 trials of Moderna and Pfizer's vaccine is truly encouraging. It means that these vaccines are quite safe.
@@MedicoVisual Yes. But let's still wait for the full data, and any potential long term effects! Second it would be interesting to know how long the protection lasts, and if vaccinated people don't develop symptoms but could still be "hidden carriers", or if they do not shed any virus at all i.e. they are sterile. But yes, generally I agree. Looks safe so far and the new technology is really amazing! Thanks for the reference btw. And thanks for your detailed explanation. Hope to see more such videos from you.
@@MultiSciGeek The mRNA vaccines don't contain the virus, so those vaccinated can't shed or be carriers. As the video shows, the spike itself can't infect a cell, may bind but can't enter it.
The basic mechanism of prophylactic mRNA vaccines is described on Moderna's official website www.modernatx.com/moderna-blog/shedding-light-our-prophylactic-vaccines-moa The details of CD4+ T cells, B cells, and CD8+ cells can be found in any immunology book. I followed "Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 13e by Warren Levinson" + Dr. Najeeb lectures (www.drnajeeblectures.com)
Question: does the spike protein float around outside the cell, or it is it presented as attached to the cell? Then the immune cell would destroy the muscle cell?
Wonderful video, very clear, also for non expert people, like I am. I have some questions, if you or anybody here can answer: 1 - could it be possible that the mRNA injected will code not just for the "S"protein but for something else, maybe risky? 2 - in general, for this kind of extremely engineered vaccines, what should be a reasonable time to detect eventual side effects? 3 - are we sure that the mRNA is perfectly cut / paste into the lipidic container? 4 - the Moderna company released the vaccine in an extremely short time frame, after the virus was officially detected: isn'it suspicious? 5 - are the current Sars-Cov2 mutations also inhibited with the same vaccine, or we could expect a mutation in the "S" protein, so to re-emgineer the vaccine? Thanks everybody for any answer and sorry if my questions can look like "stupids" or non professionals. I am a software developer and not a genetist, even if I have my theory about DNA compiling, using quantum computers :-)
@@agnieszkat8472 Hi, thanks for the answer. Yes, just for querying is not necessary, I am talking about using IDEs to create software that is not just compiled as binary program but as biological "code", so not with sequences of 0s and 1s but with sequences of ATCGs. If you have something to recommend me about this tools, if they exist, please, just give me some link / refereneces. I am seeing that quantum computing is promising for these kind of stuffs, I mean genetic prediction and developing. See here, for example: www.technologynetworks.com/informatics/news/the-power-of-quantum-computing-harnessed-for-dna-study-298183 Regards.
Omg.... The best and simple explanation ever..!! 👌 Thank you so much... I have been searching for this only... 🙏🙏 I like my native people also to be aware of this.... If u don't mind ... Can i translate your video in our languages with proper credits... !? Btw... Thank you so much for your explanation... 🙏❤️
Thank you so much. These words of appreciation compel me to work harder. I would be honoured if you translate the video. Furthermore, I am licensing these videos under CC (Creative Commons license) so you can freely use them for benefit of mankind (attribution is necessary though). Also, I am turning on the user contributions for this video. Again Thanks a lot. Stay blessed.
@@MedicoVisual And please do check our channel too... We post science topics in our other languages for native people... There are some English videos also... Please do Support us too.. 🙏❤️
Thank you so much for your appreciation. Great question! I am gonna address this in next and last part of Coronavirus visual lecture series. But to give you sneak peek: 1. History of visit to the epidemic area (Wuhan) along with symptoms fever, dry cough, malaise will raise the suspicion. 2. Diagnosed with RT-PCR from Nasopharyngeal secretions of the patient, and CT Chest (Ground glass appearance + consolidation). 3. Serology is of limited importance.
mRNA leads to release of soluble Spike protein... This can bind to ACE-2 receptors on cells throughout the body. So thete is activation of these cells without systemic damage?
Thats the mechanism of its working. S-protein will bind with the ACE-2 of Type II alveolar pneumocytes, Immune cells will destroy these infected cells and thats it. We got the immunity. I know your concerns here. 1. Some type II alveolar pneumocytes will be destroyed. Yes, thats true. But only few cells are destroyed and they are easily regenrated by the body. 2. It can lead to auto-immunity. No, thats not how autoimmunity work. It can only lead to auto-immunity, if Type II Alveolar pneumocytes keep on expressing S-proteins. Which of course, they do not.
Thank you for the detailed explanation. It was exactly what I was looking for. One question I do have is, if this method of vaccination is better than current vaccination methods, why hasn't the FDA ever approved a vaccine made this way? What were the concerns by the FDA regarding other vaccines produced this way that made them decide not to approve them after all? What portion of this mRNA vaccine could become dangerous to people and what population of people could it potentially harm and for what reasons?
Do people who are passive carriers somehow already have a natural antibody response that prevents the harmful effects that others experience? Thanks for the explainer video.
We don't know the answer clearly. Maybe they are transmitting the disease and are not showing any symptom or maybe they are neither transmitting the disease nor displaying any symptom. If you ever stumble upon a clear cut answer please do share with me as well.
Thank you. The question is suppose it was an actual virus and not a vaccine why does the cell not present those proteins on the surface? Or does it ? Is there something in the virus that prevents its proteins from being presented ? In other words, both processes between a vaccine and actual infection identical but because a vaccine isn’t replicating it gives your immune system the luxury of time to make an immune response whereas in a real infection it is a battle of time between an ever increasing virus replication vs immune response?
Yes, they are undergoing clinical trials. Here is the list: www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmv-mma-zika-several-types-cancer-and-other-diseases
The discovery of RNA is stronger than a miracle in Lourde, but in real life it may be a different story ... When you tinker with the living one can have huge surprises.
Do you think it's possible that some of mRNA that infects the muscle cells also gets translated and expressed as spike protein on the surface of the muscle cells and causes the immune system to attack the muscle cells, too? Also, are there neurons in the area of the muscle cells? Can such neurons also express the spike protein on their surface? Maybe this is behind the Bell's palsy reports observed in a small number of patients? thoughts?
I have already answered this question in another comment. I am copying and pasting that here. We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important. BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely. 🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/) P.S: I am not an expert in this field. Any insight into this by an expert would be highly appreciated. Thank you
Excelente conferencia, es el vídeo más completo y fácil de entender que he visto sobre el tema, continuaré con las otras conferencias del canal. Muchas gracias por compartir.
Thank you so much for your appreciation. Mostly it's from Levinson Medical Microbiology, Immunology part. Information regarding vaccine is available on Moderna's website (www.modernatx.com/mrna-technology/science-and-fundamentals-mrna-technology ). If you are skeptical about any specific part of the lecture. please feel free to ask, mentioning its timestamp.
@@MedicoVisual I am a Ph.D. student in Biochemistry/Molecular Cancer Biology, recently checking some interesting vids here specifically for interferon-gamma/cytokines induced immunity invasion which triggered tumorigenesis and happen to run into your video, very neat and easily illustrated (since immunology is not my background lol) keep up the great work and probably will check out more later!
Great explanation. Thank you. To my understanding, many muscle cells will die from the immune respond. But they will be replaced, so it is OK. I'm still worried that it might trigger an autoimmune disease. If normally we have spike receptors, then normally we have the spike proteins, but where, and what are they for?
Just heard the news about mRNA 1273. I have very little Biology background considering i work at IT. But this presentation was simple enough i understood the basic of how mRNA based vaccine works. And it induced my inner nerd which made me question my decision to choose CSE as my UG as opposed to genetic engineering(which i was very much interested in post higher education and seems i still do).
Thank you for sharing. I have a question: what proteins does a real sarscov2 virus produce that makes it cause disease. How does disease develop? Is there a resource you can send me to ?
th-cam.com/video/5Xo4hn18ARw/w-d-xo.html I recorded this video in Feb. It contains basic information regarding the pathogenesis of COVID- 19. The video was created on the basis of latest info available at that time but since then it has gradually became outdated. According to my current understanding, (that maybe outdated as I was busy in "Embryology" lectures so could not update myself), damage is done mainly by immune response towards the virus, rather than virus itself. Plus there is some contribution by hypercoaguable state created as a result of immune mediated damage to blood vessels. However recently, there has been some evidence that some of the proteins of this virus may suppress the immune system probably by interefering with it's communication system (www.sciencedirect.com/science/article/pii/S0168170220308170). If you want to learn more, I can recommend Medcram, Dr. John Campbell and DrBeen. They have been regularly creating update videos on COVID-19. Furthermore, you can always search Google Scholar (scholar.google.com/) for research articles. Almost every journal now a days is offering COVID related articles for free
@@MedicoVisual thank you 🙏 for all the information. Indeed science develops and it's refreshing to hear a scientists who understands that. I will look at these sources
This video is so good. Basically it cover the whole chapter of textbook and bring out the important MAIN points of what the student required to understand about the topic in 21min. The immunology concept is fundamental, however the Dr can apply to COVID-19 in this video is impressive!
Thank you so much for appreciating my work. I literally had to read 30-40 research articles and few books to get hold of the concept and then it took me a few days to summarize it as simply as possible. Please check out my other videos as well. These days I am working on Hepatitis B visual lecture series.
I don't know for sure. Maybe for certain diseases or epidemics the process of clinical trials is expedited by authorities. However, according to FDA's website, Phase III trials alone may take 1-4 years. While Phase I and Phase II may take several months. (www.fda.gov/patients/drug-development-process/step-3-clinical-research). Of course it varies on case to case basis. These timelines are just an estimate.
The H1N1 swine flu vaccine was released in the mid 1970s actually. The adverse sides effect were very significant (ie GBS - paralysis) and it was withdrawn from the market. Vaccine manufacturers were still held legally liable for product damages at that time. The exact same vaccine was re-released during the H1N1 epidemic in the late 90s.
@@MedicoVisual I really really think that gathering those data SHOULD be also part of your job. If not the most important part of the evaluations for the Human Moderna researchers..
@@MedicoVisualis not affiliated with Moderna. I"m with you. But i think lecturers, students; doctors & biotech engineers should become- and be made aware- of risk factors. If not we can be on our way to eliminate people with a vaccine and end up with those who can survive with it. But then: what is the difference with natural selection and (herd)-immunity for the virus itself. And the study of THAT. I'm not out for an argument about it on this medium. Thanks for this lecture and the reply anyway.
@@dirkdaniels5746 I agree with you. But as of now, I can not find any relevant study on Google scholar or any official source. I will definitely create an "update lecture" as soon as the study result comes out. Clinical trials are going on as per my knowledge.
Hi. I really liked your video. It is the best I have seen so far. 👍. It answered a lot of my questions. 👍👍. I am not a doctor or a scientist, but I do try to learn and understand material outside my area of expertise. That said, I have one major question remaining: How do we control which somatic cells the vaccine infects? To put it differently, how do we ensure the vaccine does not infect brain cells, for instance, or other important cells that we would not want to subject to the process described in your video? Thanks again for your video.
I had exactly the same question. I try hard but could not find a clear-cut answer to this. Maybe because Moderna is using a proprietary lipid nanoparticle so information about the dynamics of its mechanism is not publically avaiable. My best guess is that they are using some ligand on lipid nanoparticle and that ligand can only bind with the cell having a particular specific receptor for that ligand. The other mechanism may be that because they are injecting vaccine into the deltoid muscle most likely the nanoparticle will automatically enter the muscle rather than any other cell.
MedicoVisual - Visual Medical Lectures : You could be into something there. If I find an answer to our question, I will come back here and post a link.
Will this spike proteins not cause a NK cellular respons killing the vaccine infected cell ?? Causing auto immunity against the cells infected with the protein ?
Thats not how auto-immunity works. Few cells expressing that proteins will be killed, there will be mild redness at injection site. Within few days these cells will be replaced with the new ones and thats it.
Thank you for the reply😋 I still have 2 other problem with this vaccine is 1) you will inject it into muscle tissue. So the effected cells that will be destroyed is muscle cells. So won't this cause permanent atrophy of the tissue involved if the immune response is severe ? And 2) if the destroyed cells dies the contents of the cell will be spilled out in to the general circulation exposing intracellular proteins to the immunesystem which can cause an autoimmune reation to healthy tissue that was never infected by the m-RNA ?
Human body consists of about 60 trillion cells. Daily billions and billions of cells are destroyed and re-created and thats the normal cellular turnover, nothing to do with auto-immunity. So injecting vaccine into the muscle will not cause atrophy. Even if spike proteins spills into circulation, macrophages will destroy those proteins and thats the end of story. Nothing to do with auto-immunity. Now let me explain you what is the mechanism of auto-immunity. Although its a complicated process, but I will mention the basic idea. Lets say, I give you a hypothetical mRNA vaccine [Not this COVID vaccine]. That hypothetical vaccine contains mRNA for a protein that is very similar to some protein of your body [Similar, but not exactly the same]. Now when body will create antibodies against that vaccine's protein, due to structural similarity of vaccine's protein with the body proteins, some of these antibodies may cross-react with the normal body proteins and strat destroying your normal tissues. Thats the auto-immunity. and this mechanism is called "Molecular mimicry". The good news is that after rigirous human testing in clinical trials, there is no evidence that anything like this happens with this vaccine.
New updated video: Can mRNA vaccine alter your DNA? mRNA vaccine and Auto-immunity: th-cam.com/video/aC53npB_97o/w-d-xo.html
Thank you. Until now I couldn't find a video like yours. Out there there is nothing but short 4-6 minute videos with little explanation as to the bio-mechanics. Instead you satisfied my curiosity, Great job.
You're welcome!
Excellent and nicely detailed explanation. Worth mentioning that there currently are no approved mRNA vaccines.
They are coming!!💉💉💉💉
good explanstion but mRNA with lipis surrounded be able to enter bloodstream and enter other cells like brain cell?
Honestly, I don't have a clear-cut answer this question yet.
This is probably one of the most informative yet easy-to-follow lectures I've seen on this topic. Thank you for taking the time in creating and sharing this video! :)
Hi! Just wanted to come back to let you know that I just received the vaccine. This video helped me understand the process. Thank you and stay safe everyone!
Very well done! A complex topic made very understandable. Graphics were helpful too. Thank you.
You're very welcome!
01:26 "a year or so".
Yeah sure wasn't rushed was it.
Nice job. Your video has more scientifical detail than a lot of news pieces out there -- love it!
Please post your references so we can explore these topics further.
Many thanks for the excellent and informative lecture. I would love to see specific findings about a possible cytokine storm resulting upon exposure to Covid-19 or any corona virus post innoculation. I would also be very interested to know the exact contents of the mRNA vaccine and the medium on which the S proteins are cultured. It matters tremendously in terms of the safety profile and possible long-term or later term side effects that could present years or decades later. Your presentation is much appreciated. Many thanks.
Great explanation. Just wondering if we know for sure how quickly the S protein is expressed & recognised by the memory cytotoxic T cells before the release of the new virus particles from the cell?
Also would be interesting to know how the lipid nano particle actually gets into the cell. Just diffuses across? Many thanks
What mechanism brings the lipid coated mRNA package into the cell? Does it just automatically go in by itself? And how?
I wonder too.
If you search for liposomes, that should give you an idea.
It’s many years since I studied this stuff but I believe it’s a bit like exocytosis, but in reverse (and not just endocytosis cos that seems to form a vesicle as the material enters the cell through the membrane, rather than the lipid package already existing in the extra cellular space).
@@BongoWhack Thanks
If I’m not mistaken this “lipid nanoparticle” described in the video is for all intents and purposes is a virus. A virus that is used to shuttle genetic material across cell membranes and get mRNA into your cell. Here’s where a lot can go wrong. Free floating rna in you cell could theoretically recombine with other strands of rna and be taken up by another virus which could then infect you. And this technique could also lead autoimmune disorders.
Anthony Patch does a great job explaining that
What's to keep these spike proteins from bonding to cardiac muscle cells and then having killer T cells from attacking the infected heart muscle cells? Or any other vital organ cells? If the muscle cells start producing these spike proteins and then bonding to other muscle cells which the killer T cells destroy, wouldn't one lose a whole lot of muscle mass?
What if a person's cells produce these spike proteins at a faster rate than the body can kill?
What shuts off the mRNA? Will a person continue to produce these spike proteins forever? Won't the artificial mRNA continue to replicate itself?
It can not. Because the vaccine can not self-replicate. It will infect few skeletal muscle cells, leading to their destruction by cytotoxic cells and thus vaccine (mRNA) too will be lost. Thats it.
And BTW, lost cells will be replaced by new cells
@@MedicoVisual But what would happen if just one infected cell remained or was not killed off fast enough? Would the artificial mRNA replicate?
Thank you for answering these questions. I like to be informed before I have something injected into my body, and the news media seems to say just take it or you're killing grandma. This vaccine scares me because it hasn't been a year since even this video. I don't think researchers have any evidence of long term side effects. This video said human trials would take a few years. I know people are desperate, but should we throw caution to the wind?
@@nb4749 There is no artificial mRNA. mRNA is simply the sequence of nucleotides, and same "nucleotides" are used in synthesizing the vaccine as those present in nature.
If the infected cells are killed a bit longer, the person vaccinized will have redness and pain in deltoid [shoulder] muscle for a day or two, followed by recovery.
@@nb4749 Your concern regarding the safety is justified. But in real world, nothing is really "Safe". Every drug or medical procedure may incur some adverse effects in very few people. However, the potential benefits must outweight the the potential risks for a drug/vaccine to be advised.
Compare the deaths and complications associated with COVID-19 to this vaccine. Despite of rigorous testing for 10 months in thousands of people, there were no severe adverse effects. It means the adverse effects may be very very rare. Even, theoratically, I can't think of any potential severe adverse effects.
I would take this jab as soon as it becomes available in my area and will share the footage here if they allowed me to do so.
Does the nano lipid particle target or favor a specific cell?
Excellent Question. I could not find a very specific answer to this from Moderna's and Pfizer's docs. Their visuals and infographics depict the target to be the muscle cell, and hence I had depicted it the same way in this video. If you come up with a clear-cut answer, please share with me too.
@@MedicoVisual I understand that, part of the technology of mRNA vaccines carried by lipid nanoparticles, allows to generate specificity in the union with the target cells, through the technique of incorporating or "doping" the membrane of the nanoparticle with polypeptides that represent the exodomain of a virus natural that could couple to the receptors of the target cells to infect them. what I do not know is whether the mRNA vaccines currently in progress use this technique.
This was a truly amazing video. Thank you! Moderna and Pfizer should post this on their websites.
Wow, thank you!
Excellent overview. Do you feel we must hit a sweet spot with the dose? In other words too much mRNA entering too many host cells will trigger an innate immune response that is too aggressive. Dose dependent autoimmune reaction against the cells infected with the mRNA by the CD8 T cells thereby damaging a critical level of host tissue. Essentially causing a transient autoimmune disease.
How efficient is the lipid nanoparticle in getting absorbed by the muscle cell? And once it is absorbed by the cell does the RNA always make the cell express the proteins it is encoded for or could it be possible that the cell might ignore the RNA that is present and continue to behave normally? The reason I ask is that people say one of the unknowns about mRNA vaccines in general is how efficient they actually are and how many doses might be necessary. I'm wondering if that is an issue with this covid vaccine in particular. Thanks for such a great video with an awesome explanation!
Great points. As per my knowldge there is no such study that evaluated these things. Phase 3 trials of this vaccine are starting and that will reveal the efficacy of this vaccine.
Good question. Just wondering about the M OR Renée once it arrives in the sale. Could it be damaged in transit & then start coding for an entirely different protein that nobody was expecting? or are there are checks & balances along the way?
@@rinnin Thanks :-) I've almost fell off the chair laughing
Works about as good as sterile water.
Well presented & explained - thank you for making this info so accessible with easy to understand images 👍🏻🙏
I came to this video after the end-phase trial of Pfizer and Moderna mRNA vaccines and the immature approval of poor countries for Sinopharm and Sinovac traditional vaccine trying to figure out why the first ones are more effective, and indeed more expensive. Thank you for simple, and clear explanation.
You do understand that Phase one was skipped due to the declaration of a “pandemic”, right?
I haven't heard of such thing. If you know please share the link here.
MedicoVisual - Visual Medical Lectures
www.google.com/amp/s/www.livescience.com/amp/coronavirus-vaccine-trial-no-animal-testing.html
I meant to say the pre-clinical trials were skipped.
@@Rachellepollock1 Yes, they were allowed to skip pre-clinical trials. I don't have much insight about the reason for this. BTW thanks for sharing.
@polo polo phase 1 was never skipped. Its the pre-clinical phase (animal testing) that was skipped
18:26 question: I am wondering if another reason why mRNA vaccine could be better than antigen vaccine can be that eliciting MHC1 in the first place, could deliver more effective and clear cytokines messages in comparison to immune system, mainly via MHCII reactions, having to locate antigen spike proteins floating around plasma. what do you reckon of that, dear Doctors ? Besides, could MHC 1 system also elicit interferon gamma and interferon alpha thus respectively downgrading aggressive Th17 immune response and reducing initial infection load? I hope my question makes a sense.
I am a mechanical engineer and have little to no detailed knowledge of the human immune system beyond the layperson. This video was an excellent explanation of how a synthetic mRNA vaccine actually works compared to a traditional vaccine. I find this information both fascinating and a little bit creepy (intentionally reprogramming healthy cells with manufactured genetic material is seems like the plot of a Sci-Fi horror movie). Great job with this video!
Update: Moderna reports 95% effectiveness of its vacine candidate in interim analysis
th-cam.com/video/-5l7uSH5d5U/w-d-xo.html
Very nice lecture, you are doing great job and I’d say you maintain a perfect balance for being “scientific enough” for non scientists. Keep publishing new videos!
Seems like some kind of #Windows update with no patches possible in case of a problem?
I want a #Firewall because i feel like the future is full of #TrojanHorses!
Do the infected host cells continue producing the MRNA particles? If not, how/what happens to stop the production and when? If so, for how long?
It is clearly explained in the video :)
It never "produces" mRNA. Some mRNAs are dropped into the cells by lipid nanoparticle. They can not undergo self-replication. After making few spike proteins mRNA is destroyed. Cytotoxic T cells will destroy the infected muscle cells causing the redness and swelling at injection site. Within a day or two muscle will then heal.
isnt there the risk that the mechanism of the cytotoxic t cells as part of the immun reaction due the vaccine can lead to an excessive apoptosis of to much cells? especially if you have an mhc i polymorphmism- so you have got of the risk of an excessive immune response?
Good point. I think such risk may posed with a self-replicating vaccine. I don't think a therapeutic dose of this non-self-replicating mRNA vaccine can lead to such problem. However, I can't say it for sure. That's why clinical trials are there to assess such adverse effects.
My question exactly. Previous attempts to create a vaccine for the SARS virus had catastrophic results when lab animals were exposed to "a" (as in any) corona virus post innoculation. I am not clear as to the platform used for those vaccine development attempts. I am very opposed to skipping animal trials for any vaccine or pharma product.
@@terripebsworth9623 I haven't heard of that. Can you please share any link.
Is it possible after assembly of virion the spike protein fragment goes to cell surface and bind to MHC1.... How it is possible??
Need your kind response.... Thank you
what happens to body cells which express viral protein on MHC1? Will cytotoxic T cell kill that cell?
Yes, that cell will be killed. Watch this video for details th-cam.com/video/aC53npB_97o/w-d-xo.html
This is one of the best videos of immunology explained in non-medical language. I am not from a medical background but still, I understood the concepts very clearly. Thank you for your wonderful videos. I have a request. Can you make a video on the HIV lifecycle and what are the obstacles to finding a vaccine or a cure for it? Now we have a better understanding of these viruses but still no solution coming up.
Thank you so much for your appreciation. Right now I am making a visual lecture series on hepatitis B virus. I will make a video on HIV soon. Thanks again.
@David Hur Will work on it soon. Thank you
@David Hur Even I don't have any idea yet :-D I will study their literature to find out and make a video on it.
@David Hur Thanks for the link. I will check it out
Very educational and detailed video! I have a question though. I read the following comment on TH-cam and I was wondering if you could comment on it, whether it's true or not that in the Moderna vaccine (unlike Comirnaty) the CD8 T cells won't be activated?
"The Moderna mRNA vaccine has a transmembrane anchor so the spike protein will be embedded in the muscle cell plasma membrane and will tag the cell to be degraded by a macrophage via the exogenous/extracellular antigen presenting pathway. The exogenous antigen presenting pathway leads to the antigen (a piece of the spike protein in this case) being presented on Class II MHC and not on Class I MHC on these macrophages. As a result, you get CD4 Helper T cell activation and not CD8 Cytotoxic T cell activation."
thanks for the appreciation.
Well, I don't think that information being presented in this comment is correct unless it is backed by a peer-reviewed research article.
As the Moderna's vaccine infects the muscle cell, spike proteins will be processed by proteosomes and will be presented on MHC1. So cytotoxic cells will be activated.
Thank you for your service experimental animals
-Humanity
Great video. More detail on how the mRNA nano lipid enters the cell? Is a particular cell target?
Not much detail is available on this publically. Maybe bacuse of its biopatent
@@MedicoVisual Thanks. I have found this product and an interresting resource. Thanks for the videos.
organixinc.com/lipids/mc2-dlin-mc2-dma-tbfb8
www.ncbi.nlm.nih.gov/pmc/articles/PMC6383180/
@@randompuppy789 thank you for sharing
how widespread is cytotoxic CD8 response against (muscle) cells expressing S-protein? How many cells are expected to express the S-protein after vaccination? Is it just local or systemic expression?
Its localized
Best explanation out there for exactly how mRNA vaccine works, and its benefits vs other vaccines. Thank you so much
Thank you so much
Thank you for putting this video together. With mRNA vaccines being so new, I hadn't yet seen a visual explanation as to how they work. This is the EXACT type of video I was looking for. Also, despite my not working in the medical/healthcare field, I was still able to completely understand all of the concepts outlined in your video. If this vaccine were to get FDA approval and is effective against COVID-19, I would be very excited at the prospect of mRNA vaccine technology being applied to other viral diseases!
Such an excellent video with amazing graphic content.
Thank you for you explanation. I just got the Pfizer BioNTech Vaccin and really wanted to understand what was happening in my body. I can confidently say now that, at least on a basic level, I do. So thank you for your work!
Glad it was helpful!
So I read in phase II data that some developed binding antibody (to the cell expressing the antigen) and some developed neutralizing antibodies to the virus itself. Couldn’t the former cause an autoimmune reaction?
No, it's not like that. Antibodies are usually produced against different parts of several different proteins of coronavirus. An ideal antibody should not just "Bind" with the antigen (viral protein), but also prevent it from causing any damage to the host (human). That means this antibody should not only "just" bind but also "Neutralize" the harmful effect of the virus. SuNeutralizingody is called the "Neutralzing antibody."
For example, an ideal antibody against the Spike protein of coronavirus should bind with the spike and prevent it from attaching with the ACE2 receptors in the human lungs.
Sometimes, the antibody may just "bind" with the Spike protein (or any other antigen of the virus), but DO NOT prevent (neutralize) it's the harmful effects i.e., It binds but does not prevent the spike from attaching ACE2 receptors. This antibody is NOT "Neutralizing antibody"; it is just a "Binding antibody."
Remember, a "Neutralizing antibody" is also a "binding antibody." But the Binding antibody may not always be neutralizing.
Finally, if the body produces an antibody that does not even bind to any part of the virus, it is neither a neutralizing antibody nor a binding antibody. (It is just a redundant antibody.)
So the best antibody or the ultimate goal of a vaccine is to produce the highest quantity of "Neutralizing Antibodies," but "Binding Antibodies" do help to some extent and thus are desirable as well. For example, they can bind with the virus, thus tagging it as a dangerous substance, so the immune system may quickly destroy it even before it can cause harm.
That's a very good explanation. A doubt. As it is a RNA virus, which has tendency to mutate over time. Will this vaccine still be effective against this virus?
Thanks for your appreciation.
We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important.
BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely.
🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/)
P.S: I am not an expert in this field. Any insight into this by an expert would be highly appreciated. Thank you
Is this also the body's natural response to exposure of a virus? If this is the immune response to the introduction of mRNA, how does it differ from the naturally occurring response when directly exposed to the virus? For example, if someone is exposed to the virus, is infected, and then successfully fights it and recovers; isn't the end result the same as exposure to mRNA vaccine? Are CD8, B Lymphocyte, and CD4 cells not produced in the same way? I guess I don't understand how an mRNA vaccine is more effective at fighting future infections than the body's natural response after the body has been exposed, naturally develops an immune response, and then in exposed again in the future.
Yes, you are right. Natural response is pretty much the same. I don't think vaccine is more effective than the natural immunity. They only reason I can think of id that in case of vaccine, 2 doses are given. The second (booster) dose may thus improve the immunity formed by 1st dose. Other than that theoratically, a single dose of vaccine and natural immunity should be equally effective.
Firstly full appreciation for your quite explanation, but I’ve single question:
Why not MHC II to present the S protein on the cell surface?
By rule, MHC II is used to present the protein fragments only by "Professional" Antigen Presenting cells e.g. Macrophages. Other cells can only use MHC I. Its an established fact in immunology. Don't know the exact reason though.
Great work - Thanks heaps for this video. I was wondering how long this whole process takes? From the vaccine entering your body to when the mRNA infected cells are destroyed. Minutes, hours or days? Would love a timeline.
Protein vaccines can be presented on MHC I though cross presentation by dendritic cells though, right ? Otherwise, great presentation thanks a lot !
What if something useful in our body or something useful in the future uses that exact same spike protein?
Its a viral protein. Why would body use it ?
@@MedicoVisual Ok I just watched your Transverse myelitis video and in there it's exactly what I mean. What if (I am not saying it is true), but due to vaccine the body might start attacking it's own cells or whatever which have a similar spike protein? Exactly what we saw in transverse Myelitis video.
@@MultiSciGeek well, theoratically it can happen. But in reality, it is very unlikely. Let me tell you why:
1. If spike protein resembled some important bodily protein, there would have been a whole lot of cases of autoimmune diseases caused by natural COVID-19 infection by now. But despite of literally millions of people infected with COVID-19 there are little to no cases of autoimmune diseases followed by disease (there are some cases out there but it is not statistically significant to consider that they are caused by Sars-CoV-2 and precisely by "spike" protein of spike protein)
2. Moderna and Pfizer had enrolled more than 30000 participants in their clinical trials yet no one experienced such illness.
3. Although there were few cases of neurological illness with Oxford's vaccine. It is less likely due the spike protein. Oxford's vaccine uses Chimpanzae's Adenovirus that has its own protein receptors. That may be the culprit rather than spike protein. Furthermore, they haven't revealed that the ilness was due to vaccine or not. (Personally, I think Moderna's and Pfizer's vaccine should be much safer than Oxford's and even CanSino's vaccine due to a single antigen i.e Spike protein only).
Please note that I am not against Oxford's vaccine but I won't trust it unless it gets approved by FDA or they reveal the data to the public.
Great talk. How long is the new antigen detectable in the tissue and in the serum?
We need to begin a warp speed program to develop a method of research that does not involve torturing animals!!!!!
The solution is simple, we torture human instead.
Would genetic differences in MHC1 affect the presentation of this protein and therefore affect immune response?
Yes, it does. And that may be the reason of different immune response in population.. Google MHC polymorphism to learn more
@@MedicoVisual would it affect the ability of the vaccine to produce an immune response?
@@marypatterson3246 I think, yes, it could.
@@marypatterson3246 No vaccine has 100% efficacy.
Sir I have some doubt ... surface spike protein are continuously changes so our specific immune response does not recognise ..
This mRNA 1273 vaccine generate stable spike protein then only single specific spike protein antibodies made .. how infection is prevented 😃
You mean continuously mutating ?
I would love to answer this but can you please elaborate.
I had a similar question. What happens if there is mutation in the virus which changes the spike protein slightly? Wouldn't that mean the antibodies produced from this vaccine would no longer bind to this mutated virus?
This is basically the influenza situation with antigenic drift but maybe coronaviruses are more stable. Do we know how stable has the spike protein been as this virus has spread worldwide?
@@Free-g8r That's a great question. We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important.
BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely.
🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/)
P.S: I am not an expert of this field. Any insight into this by an expert would be highly appreciated. Thank you
I didn't understand why, when the mrna is injected it can not cause the disease ? How does mrna enter the cell althought it has no spike protein which binds to the ACE2 ?
1. Because it is not self-replicating.
2. Lipid nanoparticle is used to drop the mRNA into cell
@@MedicoVisual 1)Although coronavirus can replicate its self, why mRNA is not self-replicating ? 2)In which part of the cell you drop the mRNA, nucleus? cytoplsme ? Thank you for your answer.
@@zehravigna4873 1. Simply because they have removed the "Replicase" enzyme's part from RNA, only spike protein's part is present
2. Its dropped in cytoplasm
@@MedicoVisual You say that it is dropped in cytoplasm. But when the doctor is applying the vaccine on the arm (or somewhere else), when he pushes the needle, how does he know that the area where he inject the vaccine is the cytoplasme and not the nucleus ?
Indeed. The excellent lecture. However, I have a question. Is the mRNA + lipid (PEG) going to enter into a specific cell or it will target randomly by entering into different cells such as heart, nerve, brain, liver, kidney or. other.
Most these Phase 3 trials have upwards of 30,000 participants!
Yes, generally phase 3 clinical trials consist of 3000 participants (Ref: Basic And Clinical Pharmacology
Book by Bertram G. Katzung).
The fact that they enrolled 30000-50000 participants in phase 3 trials of Moderna and Pfizer's vaccine is truly encouraging. It means that these vaccines are quite safe.
@@MedicoVisual Yes. But let's still wait for the full data, and any potential long term effects! Second it would be interesting to know how long the protection lasts, and if vaccinated people don't develop symptoms but could still be "hidden carriers", or if they do not shed any virus at all i.e. they are sterile.
But yes, generally I agree. Looks safe so far and the new technology is really amazing!
Thanks for the reference btw.
And thanks for your detailed explanation. Hope to see more such videos from you.
@@MultiSciGeek The mRNA vaccines don't contain the virus, so those vaccinated can't shed or be carriers. As the video shows, the spike itself can't infect a cell, may bind but can't enter it.
@@a.cuevas1065 I meant after infection obviously
Anthony Patch does a great job explaining this a little better & in more detail, you can find him on TH-cam
Share the link. Could not find it
Thank you so much for this clear explanation. Great presentation.
any references for this mode of action? since i cant find the reference to say this chronology is valid to mrna 1273.to validate the data,
The basic mechanism of prophylactic mRNA vaccines is described on Moderna's official website www.modernatx.com/moderna-blog/shedding-light-our-prophylactic-vaccines-moa
The details of CD4+ T cells, B cells, and CD8+ cells can be found in any immunology book. I followed "Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 13e
by Warren Levinson" + Dr. Najeeb lectures (www.drnajeeblectures.com)
Question: does the spike protein float around outside the cell, or it is it presented as attached to the cell? Then the immune cell would destroy the muscle cell?
yes it does destroy the muscle cell but only very few of them
th-cam.com/video/aC53npB_97o/w-d-xo.html Watch this video for detailed explanation of this concept.
Watching this was so informing. I think I never learned so much in such a short time period. Thank you!
Thank you so much for your appreciation
Wonderful video, very clear, also for non expert people, like I am. I have some questions, if you or anybody here can answer:
1 - could it be possible that the mRNA injected will code not just for the "S"protein but for something else, maybe risky?
2 - in general, for this kind of extremely engineered vaccines, what should be a reasonable time to detect eventual side effects?
3 - are we sure that the mRNA is perfectly cut / paste into the lipidic container?
4 - the Moderna company released the vaccine in an extremely short time frame, after the virus was officially detected: isn'it suspicious?
5 - are the current Sars-Cov2 mutations also inhibited with the same vaccine, or we could expect a mutation in the "S" protein, so to re-emgineer the vaccine?
Thanks everybody for any answer and sorry if my questions can look like "stupids" or non professionals. I am a software developer and not a genetist, even if I have my theory about DNA compiling, using quantum computers :-)
You don't need a quantum computer to search through a virus database for Corona viruses and fuse/select interesting sequences especially for 'Spikes'
@@agnieszkat8472 Hi, thanks for the answer. Yes, just for querying is not necessary, I am talking about using IDEs to create software that is not just compiled as binary program but as biological "code", so not with sequences of 0s and 1s but with sequences of ATCGs.
If you have something to recommend me about this tools, if they exist, please, just give me some link / refereneces.
I am seeing that quantum computing is promising for these kind of stuffs, I mean genetic prediction and developing. See here, for example:
www.technologynetworks.com/informatics/news/the-power-of-quantum-computing-harnessed-for-dna-study-298183
Regards.
Omg.... The best and simple explanation ever..!! 👌
Thank you so much... I have been searching for this only... 🙏🙏
I like my native people also to be aware of this....
If u don't mind ... Can i translate your video in our languages with proper credits... !?
Btw... Thank you so much for your explanation... 🙏❤️
Thank you so much. These words of appreciation compel me to work harder. I would be honoured if you translate the video. Furthermore, I am licensing these videos under CC (Creative Commons license) so you can freely use them for benefit of mankind (attribution is necessary though). Also, I am turning on the user contributions for this video. Again Thanks a lot. Stay blessed.
@@MedicoVisual Thank you so much... 🙏❤️
@@ThiNKBiologyThiNKVISION Please do check my other videos as well. I just uploaded the video on the diagnosis of COVID-19 with special emphasis on PCR
@@MedicoVisual yeah checking it... Of course glad to support ur work...! 🤝😊
@@MedicoVisual And please do check our channel too... We post science topics in our other languages for native people... There are some English videos also...
Please do Support us too.. 🙏❤️
Are control groups used?
I guess, No. See the details here: clinicaltrials.gov/ct2/show/NCT04283461?term=mRNA+1273&draw=2&rank=1
How to diagnose for SARS-CoV-2? Love this series btw.
Thank you so much for your appreciation. Great question! I am gonna address this in next and last part of Coronavirus visual lecture series.
But to give you sneak peek:
1. History of visit to the epidemic area (Wuhan) along with symptoms fever, dry cough, malaise will raise the suspicion.
2. Diagnosed with RT-PCR from Nasopharyngeal secretions of the patient, and CT Chest (Ground glass appearance + consolidation).
3. Serology is of limited importance.
Thanks a lot and I’ll wait the forthcoming videos really they are so useful
Excellent video! finally one video really explains in detailed the CD8 and CD4 response! thank you
Thanks very much for the detailed explanation. Very educational.
mRNA leads to release of soluble Spike protein... This can bind to ACE-2 receptors on cells throughout the body. So thete is activation of these cells without systemic damage?
Thats the mechanism of its working. S-protein will bind with the ACE-2 of Type II alveolar pneumocytes, Immune cells will destroy these infected cells and thats it. We got the immunity. I know your concerns here.
1. Some type II alveolar pneumocytes will be destroyed. Yes, thats true. But only few cells are destroyed and they are easily regenrated by the body.
2. It can lead to auto-immunity. No, thats not how autoimmunity work.
It can only lead to auto-immunity, if Type II Alveolar pneumocytes keep on expressing S-proteins. Which of course, they do not.
Thank you for the detailed explanation. It was exactly what I was looking for. One question I do have is, if this method of vaccination is better than current vaccination methods, why hasn't the FDA ever approved a vaccine made this way? What were the concerns by the FDA regarding other vaccines produced this way that made them decide not to approve them after all? What portion of this mRNA vaccine could become dangerous to people and what population of people could it potentially harm and for what reasons?
I don't think mRNA could pose any danger to people. Perhaps Moderna's or Pfizer's mRNA vaccine will be the first ones to bag FDA's approval
Awesome so clear explanation... THX so much! 👍👌
Thank you
Do people who are passive carriers somehow already have a natural antibody response that prevents the harmful effects that others experience? Thanks for the explainer video.
We don't know the answer clearly. Maybe they are transmitting the disease and are not showing any symptom or maybe they are neither transmitting the disease nor displaying any symptom. If you ever stumble upon a clear cut answer please do share with me as well.
JML Stone
Honorary Advisor (retired) to the National Advisory Council of the Thalidomide Trust
London 🇬🇧
Excellent and very informative and in detailed.. thank you so much for each and every step of mRNA vaccine... Excellent job Madam.
Thank you so much for appreciation. Except that I am not Madam. I am Sir :-D . Lol
Thank you. The question is suppose it was an actual virus and not a vaccine why does the cell not present those proteins on the surface? Or does it ? Is there something in the virus that prevents its proteins from being presented ? In other words, both processes between a vaccine and actual infection identical but because a vaccine isn’t replicating it gives your immune system the luxury of time to make an immune response whereas in a real infection it is a battle of time between an ever increasing virus replication vs immune response?
how does mRNA in vaccine gets into the cells or it is meant to be used by cells in blood?
Immune system is really a blessing 😇😇. Being so super-working, it is so intricate as well.
Yes it is, indeed.
Is there mRMA for any other viral disease
Yes, they are undergoing clinical trials. Here is the list: www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmv-mma-zika-several-types-cancer-and-other-diseases
Thanks for wonderful animated lecture and technical information 👍
@@hellokitkats you are most welcome. Thank you for your appreciation.
The discovery of RNA is stronger than a miracle in Lourde, but in real life it may be a different story ... When you tinker with the living one can have huge surprises.
Good or bad surprises ?
Thank you so much! You answered all of my questions!
You are most welcome
MedicoVisual - Visual Medical Lectures 😊
Do you think it's possible that some of mRNA that infects the muscle cells also gets translated and expressed as spike protein on the surface of the muscle cells and causes the immune system to attack the muscle cells, too? Also, are there neurons in the area of the muscle cells? Can such neurons also express the spike protein on their surface? Maybe this is behind the Bell's palsy reports observed in a small number of patients? thoughts?
please watch this video: th-cam.com/video/aC53npB_97o/w-d-xo.html
Excelent my friend. Is the best technical demonstration of thw action and used mRNA 👏👏👏
Thank you so much.
A wonderful lecture explaining this approach to this type of vaccine technology.
Thank you so much for this invaluable information and really helps us all understand how this works.
Thanks for watching and appreciating my work
Can the spike proteins change from strain to strain? Meaning the vaccine could only affect certain strains? Or all strains?
I have already answered this question in another comment. I am copying and pasting that here.
We don't know for sure. The virus can mutate enough to generate a totally different S-protein for which this vaccine might not work. But slight changes in structure might offer a cross-resistance. Especially with the mRNA vaccine. Because the mRNA vaccine stimulates cell-mediated arm of immunity as well. and cell-mediated immune arm recognizes small protein fragments. In theory, even if spike protein changes slightly, most of the fragments of S-protein will still be the same. So theoretically it can provide a better cross-resistance against different strains. However, we can't say with certainty that what results it yields in the real-world, and that's exactly why clinical trials are important.
BTW I have a found a news article (authenticity questionable), that reads "Nextstrain co-founder Trevor Bedford said the mutations are so small that there is no strain of the virus that is more harmful." So It means if mutations are small, S-protein might not change so much and vaccines might work nicely.
🙂 (Source: nypost.com/2020/03/29/at-least-8-strains-of-the-coronavirus-are-spreading-across-the-globe/)
P.S: I am not an expert in this field. Any insight into this by an expert would be highly appreciated. Thank you
@@MedicoVisual but if people can be reinfected 3 months later, doesn't that show that the virus proteins have been significantly modified?
Excelente conferencia, es el vídeo más completo y fácil de entender que he visto sobre el tema, continuaré con las otras conferencias del canal. Muchas gracias por compartir.
Though I can not understand spanish, Google translate helped me interpret these lines. Thanks a lot for your appreciation of my work. Stay blessed.
And when it’s starts coding for something else because Of errors?
Nothing much will happen. Protein will be destroyed
Wonderful lecture sir..Can u pls share us the source or reference of your lecture?
Thank you so much for your appreciation. Mostly it's from Levinson Medical Microbiology, Immunology part. Information regarding vaccine is available on Moderna's website (www.modernatx.com/mrna-technology/science-and-fundamentals-mrna-technology ). If you are skeptical about any specific part of the lecture. please feel free to ask, mentioning its timestamp.
very very presious thanks
Thank you too
This is such a great lecture and absolutely a great presentation !!
Thanks a lot for your appreciation.
@@MedicoVisual I am a Ph.D. student in Biochemistry/Molecular Cancer Biology, recently checking some interesting vids here specifically for interferon-gamma/cytokines induced immunity invasion which triggered tumorigenesis and happen to run into your video, very neat and easily illustrated (since immunology is not my background lol) keep up the great work and probably will check out more later!
@@andyl3655 Sir! I am honored. Thanks for watching it. Glad to see you here.
Great explanation. Thank you.
To my understanding, many muscle cells will die from the immune respond. But they will be replaced, so it is OK.
I'm still worried that it might trigger an autoimmune disease.
If normally we have spike receptors, then normally we have the spike proteins, but where, and what are they for?
No we dont have spike proteins normally
Just heard the news about mRNA 1273. I have very little Biology background considering i work at IT. But this presentation was simple enough i understood the basic of how mRNA based vaccine works. And it induced my inner nerd which made me question my decision to choose CSE as my UG as opposed to genetic engineering(which i was very much interested in post higher education and seems i still do).
I am glad that it sparked the interest. I love medical teaching. Thanks a lot for watching.
Bioinformatics is a crossover "option" for IT ppl
Thank you for this detailed explanation! 🙏
Thank you for sharing. I have a question: what proteins does a real sarscov2 virus produce that makes it cause disease. How does disease develop? Is there a resource you can send me to ?
th-cam.com/video/5Xo4hn18ARw/w-d-xo.html
I recorded this video in Feb. It contains basic information regarding the pathogenesis of COVID- 19. The video was created on the basis of latest info available at that time but since then it has gradually became outdated.
According to my current understanding, (that maybe outdated as I was busy in "Embryology" lectures so could not update myself), damage is done mainly by immune response towards the virus, rather than virus itself. Plus there is some contribution by hypercoaguable state created as a result of immune mediated damage to blood vessels.
However recently, there has been some evidence that some of the proteins of this virus may suppress the immune system probably by interefering with it's communication system (www.sciencedirect.com/science/article/pii/S0168170220308170).
If you want to learn more, I can recommend Medcram, Dr. John Campbell and DrBeen. They have been regularly creating update videos on COVID-19.
Furthermore, you can always search Google Scholar (scholar.google.com/) for research articles. Almost every journal now a days is offering COVID related articles for free
@@MedicoVisual thank you 🙏 for all the information. Indeed science develops and it's refreshing to hear a scientists who understands that. I will look at these sources
Very clear and educational video, thank you.
Thank you
Such a great lecture... Really inspired..
Thank you so much for your appreciation. Please check out other videos on my channel as well if you are interested.
This video is so good. Basically it cover the whole chapter of textbook and bring out the important MAIN points of what the student required to understand about the topic in 21min. The immunology concept is fundamental, however the Dr can apply to COVID-19 in this video is impressive!
Thank you so much for appreciating my work. I literally had to read 30-40 research articles and few books to get hold of the concept and then it took me a few days to summarize it as simply as possible. Please check out my other videos as well. These days I am working on Hepatitis B visual lecture series.
@@MedicoVisual doctor thanks for your explanation!!!
Excellent and clear presentation. Thank you
Thanks a lot
Why did the H1N1 (swine) flu vaccine come out in 6 months but this one will take longer (1 yr)
I don't know for sure. Maybe for certain diseases or epidemics the process of clinical trials is expedited by authorities. However, according to FDA's website, Phase III trials alone may take 1-4 years. While Phase I and Phase II may take several months. (www.fda.gov/patients/drug-development-process/step-3-clinical-research). Of course it varies on case to case basis. These timelines are just an estimate.
The H1N1 swine flu vaccine was released in the mid 1970s actually. The adverse sides effect were very significant (ie GBS - paralysis) and it was withdrawn from the market. Vaccine manufacturers were still held legally liable for product damages at that time. The exact same vaccine was re-released during the H1N1 epidemic in the late 90s.
@@terripebsworth9623 was it the exact same virus that was re-released in the 90s given the important side effects or was it modified?
This is only a 100% best case scenario...what about the % of side effects and what 'kind of' could they be?
I don't know. If you have the data can you please share?
@@MedicoVisual I really really think that gathering those data SHOULD be also part of your job. If not the most important part of the evaluations for the Human Moderna researchers..
@@dirkdaniels5746 MedicoVisual is not affiliated with Moderna in any way. We just create medical lectures for medical students and doctors. :-)
@@MedicoVisualis not affiliated with Moderna. I"m with you. But i think lecturers, students; doctors & biotech engineers should become- and be made aware- of risk factors. If not we can be on our way to eliminate people with a vaccine and end up with those who can survive with it. But then: what is the difference with natural selection and (herd)-immunity for the virus itself. And the study of THAT. I'm not out for an argument about it on this medium. Thanks for this lecture and the reply anyway.
@@dirkdaniels5746 I agree with you. But as of now, I can not find any relevant study on Google scholar or any official source. I will definitely create an "update lecture" as soon as the study result comes out. Clinical trials are going on as per my knowledge.
Hi. I really liked your video. It is the best I have seen so far. 👍. It answered a lot of my questions. 👍👍. I am not a doctor or a scientist, but I do try to learn and understand material outside my area of expertise. That said, I have one major question remaining: How do we control which somatic cells the vaccine infects? To put it differently, how do we ensure the vaccine does not infect brain cells, for instance, or other important cells that we would not want to subject to the process described in your video?
Thanks again for your video.
I had exactly the same question. I try hard but could not find a clear-cut answer to this. Maybe because Moderna is using a proprietary lipid nanoparticle so information about the dynamics of its mechanism is not publically avaiable. My best guess is that they are using some ligand on lipid nanoparticle and that ligand can only bind with the cell having a particular specific receptor for that ligand. The other mechanism may be that because they are injecting vaccine into the deltoid muscle most likely the nanoparticle will automatically enter the muscle rather than any other cell.
BTW thanks a lot for your appreciation
MedicoVisual - Visual Medical Lectures : You could be into something there. If I find an answer to our question, I will come back here and post a link.
@@lajesq176 thank you
Will this spike proteins not cause a NK cellular respons killing the vaccine infected cell ?? Causing auto immunity against the cells infected with the protein ?
Thats not how auto-immunity works. Few cells expressing that proteins will be killed, there will be mild redness at injection site. Within few days these cells will be replaced with the new ones and thats it.
Thank you for the reply😋 I still have 2 other problem with this vaccine is 1) you will inject it into muscle tissue. So the effected cells that will be destroyed is muscle cells. So won't this cause permanent atrophy of the tissue involved if the immune response is severe ? And 2) if the destroyed cells dies the contents of the cell will be spilled out in to the general circulation exposing intracellular proteins to the immunesystem which can cause an autoimmune reation to healthy tissue that was never infected by the m-RNA ?
Human body consists of about 60 trillion cells. Daily billions and billions of cells are destroyed and re-created and thats the normal cellular turnover, nothing to do with auto-immunity. So injecting vaccine into the muscle will not cause atrophy. Even if spike proteins spills into circulation, macrophages will destroy those proteins and thats the end of story. Nothing to do with auto-immunity.
Now let me explain you what is the mechanism of auto-immunity. Although its a complicated process, but I will mention the basic idea.
Lets say, I give you a hypothetical mRNA vaccine [Not this COVID vaccine]. That hypothetical vaccine contains mRNA for a protein that is very similar to some protein of your body [Similar, but not exactly the same]. Now when body will create antibodies against that vaccine's protein, due to structural similarity of vaccine's protein with the body proteins, some of these antibodies may cross-react with the normal body proteins and strat destroying your normal tissues. Thats the auto-immunity. and this mechanism is called "Molecular mimicry".
The good news is that after rigirous human testing in clinical trials, there is no evidence that anything like this happens with this vaccine.
Very helpful, thank you!
No worries!