COVID-19: Vaccines

by Sean Elliott, MD

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    00:01 COVID-19 Vaccines.

    00:04 Vaccines in general, are the best tool for prevention against any infectious disease.

    00:09 And for them to be effective and to be accepted, as being effective and again this is any infection, it should be at least 50% effective.

    00:18 Specific to COVID-19 and the SARS-Coronavirus II vaccines, the initial requirements in the United States, were that the new vaccine products, be at least 50 % effective.

    00:29 Now, as we are moving forward into the current, there are many vaccine products, including a vaccine product, which has been tested and found to be safe and effective in children from ages 12 years of age and up.

    00:43 This is the Pfizer messenger RNA vaccine, which showed 100 % efficacy against COVID-19, in this young age group.

    00:52 So, vaccines are always the best tool for prevention as noted and luckily, the COVID-19 pandemic, has triggered creation of very successful vaccines, even when compared to the influenza vaccine, which is perhaps one of the most common and upheld successful interventions.

    01:10 The influenza vaccine, typically 40% to 60% effective in any epidemic year, but, it is still quite useful in preventing severe disease and preventing an overburdening of the healthcare system.

    01:23 Full vaccines then, are recommended for everybody, including those who have had prior COVID-19, since it has been demonstrated that patients with mild to even moderate COVID-19, have a risk of second infections or even third infections and vaccines provide a robust, high level of antibody protection against currently the spike protein, which is, quite protective even for those who have had prior infection.

    01:51 So, at least in the States the CDC recommends vaccines, for all individuals despite their prior infection status.

    01:59 However, full vaccination meaning a full either two doses, for a two dose vaccine, or one dose for the Johnson Johnson vaccine, which is a one dose vaccine, but full vaccines remain controversial.

    02:13 Again, it is unclear exactly whether a previously infected person requires just one dose of vaccine to get robust protection or whether having the two doses, will provide long-lasting and robust protection.

    02:28 So, as of the time of this this lecture, that issue remains unresolved, but currently at least individuals previously infected, do require vaccine of some sort.

    02:39 What are the types of vaccine methodologies? And we start with the products by AstraZeneca and Johnson and Johnson, similarly, Russia’s products Sputnik V, follows this methodology as well, these are vaccines which include a non-replicating adenovirus as the vector or the carrier for a gene encoding the spike protein of SARS-Coronavirus II.

    03:04 The next category are the vaccines made by Pfizer and Moderna.

    03:10 These are messenger RNA vaccines in which, the messenger RNA, specifically and only for the S-protein gene, are included in a nanoparticle encapsulated lipid particle construct, which then, triggers immune reaction.

    03:27 And then a vaccine produced by Novavax, takes the actual spike protein itself the S1-protein, coats it with synthetic nanoparticles and then provides it in an immune boosting adjuvant, which triggers immune reaction.

    03:42 So, in general, how do vaccines work? Well, we know that vaccines work by triggering, a specific adaptive immune response, by the human immune system, which then, creates memory, so, that the individual's immune system, can react to subsequent challenge, by that same antigenic challenge.

    04:01 Looking specifically at the messenger RNA based vaccines and this this is newer technology to most of us, it is really quite unique and exciting as a platform for vaccines, because this process will work for other infectious diseases as well.

    04:18 In a messenger RNA based vaccine against SARS-Coronavirus II, the messenger RNA code for the spike protein the S1-protein gene, is introduced into the human body, where, it is taken up or absorbed by antigen presenting cells, as with any other antigen delivery via vaccine.

    04:43 However, those antigen presenting cells, as they ingest the messenger RNA, then go through translation and transcription processes, to create the spike protein and then express the spike protein, at their cell surface along with MAC classes 1 and 2 and or, release the spike protein where it is then able to be ingested and to trigger an immune response, by other antigen presenting cells.

    05:10 So, here, we see the delivery vehicle, the messenger RNA vaccine, with the messenger RNA code, for the spike protein in its little nanoparticles, it then is taken up as the full construct by the anti-presenting cell, the messenger RNA is introduced into the anti-presenting cell, where, it is translated into spike protein, the spike protein then is expressed at the cell surface, with MAC class 1 and 2 to T-lymphocytes and B-lymphocytes, which, are the next stage and or secreted externally to where it is then taken up by other antidepressant cells in the same process and that then drives the adaptive immune response using T-lymphocytes the CD4+ T-helper T-lymphocytes and B-lymphocytes to create specific immunoglobulins.

    06:05 So, that is the strategy, does it work? Now, this this is a historic slide, but it shows in the United States, the most recent surge or peak, which occurred in the winter of 2021, in the States and you can see on the slider front of you, around, I guess it was December, is when,w max vaccinations started in the United States and it took quite some time of course, to get to anything resembling a decent vaccine coverage and in fact, currently the United States in general, is hovering around, 50% maybe 54% total fully vaccinated and just a little bit more who have received at least one dose.

    06:52 However, as that vaccine coverage has rolled out, one can see a decrease in the number of cases quite robustly, as we go into spring of 2021.

    07:03 So, that would suggest that the vaccine efficacy was excellent.

    07:07 What is vaccine efficacy? It is, the degree to which a vaccine prevents disease and potentially also transmission, so, preventing infectivity is important, under ideal or controlled circumstances.

    07:21 Typically, one creates an estimate of the efficacy of any intervention, whether it's in this case a vaccine or medication or something similar, by comparing that that test group, the vaccinated group, with a placebo group, so, efficacy is how well it prevents disease and potentially transmission disease.

    07:41 That's what's predicted in a laboratory-controlled setting or a can a clinical study in which everything is controlled.

    07:48 What about real world or population level data? This is what is known as the effectiveness estimate.

    07:55 This is how well in this case the vaccine actually performs in the real world.

    07:59 As you would imagine, that the real world numbers are going to be lower than the carefully controlled efficacy numbers.

    08:07 But that's okay, as long as the effectiveness is adequate.

    08:10 What one is really looking for of course, is, how effective is the intervention the vaccine against infection? does it do its job in the real world setting and this is the number the effectiveness against infection, that the FDA signed, an a hoped for value of 50%.

    08:30 As it turns out that that target was exceeded significantly, by most vaccine products currently available, in the United States and Europe and even parts of India and Africa.

    08:44 So, most vaccines are up to 90% effective against symptomatic infection, so, that is fantastic.

    08:52 And of course, on a personal level one wants a product a vaccine which will protect one from infection period.

    08:59 However, in terms of major use of resources, the absolute morbidity, the challenge that all countries have faced, in the COVID-19 pandemic, has been the burden on health care infrastructure, so, what one really wants to prevent that challenge, is, effectiveness against severe disease.

    09:19 How well does the vaccine do against a disease, which requires, the patient to be hospitalized and to consume health care resources and of course, this is the most important factor, not just to prevent death, which is ideal, but also prevent use of the healthcare system.

    09:37 And again, major vaccines, certainly the messenger RNA vaccines and several of the adenovirus vector vaccines, are near or at 100% effectiveness against severe disease, that's fantastic.

    09:51 Okay, let's fast forward into the real world, one more step and that is knowing that as we attempt to control, the SARS-Coronavirus II in nature, nature abhors a vacuum and new variants, mutations are occurring all the time.

    10:07 How well do the vaccines do, in effectiveness against the new virus variants? And especially the delta variant which is the current challenge, being faced by the United States.

    10:17 Yes, there are variations in effectiveness, but in general, the currently available vaccines worldwide, remain effective against the new variants of concern, that have been identified to this point.

    10:30 Most of the vaccines do better against severe disease, even against the variants, but all of them have at least some protection, even as low as 50% against the new variance of concern.

    10:42 As we speak, however, surveillance on goes all across the world and new vaccines are still in development, so, any slide regarding this is likely going to be dated, by the time you're watching it.

    10:53 Now, vaccines are fantastic, but they are also an intervention, a medical science intervention and so there will be side effects, most of which are minor.

    11:04 So, the minor side effects identified with the vaccines noted so far, are, a flu-like illness, so soreness at the injection site of course, which, will last a couple days to a week and accompanied sometimes by malaise, low-grade fevers, some sore muscles and that basically reflects a very excellent immune response, by the vaccine recipients.

    11:27 Thankfully, major side effects and certainly fatal side effects have been incredibly rare, that's a wonderful thing and that of course then drives the question, was that incredibly rare, “I hadn't seen it before side effect,” in my single vaccine recipient, due to the vaccine, or was it something related to health issues, pre-existing in the vaccine recipient and in many cases it's very difficult to tell, as proof of causality is difficult to achieve.

    11:58 So, as an example there have been evidence episodes of myocarditis, in vaccine recipients of one of the messenger RNA vaccines, Pfizer or Moderna, mostly young men and those incidence, numbers of myocarditis, in those individuals have exceeded the rate normally witnessed, in a non-vaccine, non-covid pandemic time.

    12:25 So, that would suggest that there is some association, why we don't know, but some association, with messenger RNA vaccination and myocarditis, in certain individuals.

    12:37 So, what are the side effects that we've witnessed, anaphylaxis, of course, would be a severe side effect, anaphylaxis is possible with any vaccine.

    12:46 Fortunately, for the messenger RNA vaccines, in which some episodes have been reported, this is an incredibly low incident, so just 3 to 5 per million vaccine recipients, mostly in women who had pre-existing severe environmental allergies or allergies to food or other products.

    13:05 The incidence of thrombosis and thrombocytopenia and specifically, a heparin induced or vaccine-induced immune thrombocytopenia, has been demonstrated in patients who received one of the adenovirus vectored vaccines mostly AstraZeneca and Johnson and Johnson.

    13:25 These individuals, have had some significant effects of this thrombosis, including cerebral venous thrombosis and splanchnic vein thrombosis, are the two most common, thrombotic illnesses witnessed in these individuals.

    13:42 With the AstraZeneca vaccine, out of 34 million doses administered, you can see the numbers there, just 169 episodes of cerebral venous thrombosis and 53 episodes of splanchnic vein thrombosis, have been demonstrated and confirmed with 18 deaths and based on that, although it is an incredibly rare risk, but the risk is felt to be real.

    14:04 So, in many countries, AstraZeneca, is not given to vaccine recipients, who are under age 60, because these cerebral venous and splanchnic venous thrombotic events, all occurred in young adults.

    14:17 In the Johnson and Johnson vaccine, out of 20 million doses administered, 25 cases and 9 deaths respectively, with vaccine associated thrombotic thrombocytopenia.

    14:30 So, if we then try and compare the risk of vaccine effects, whether they're minor or major or severe or fatal, to other adverse effects, these are great these are great talking points, if one is having this conversation with one's patients, the lifetime chance of dying in a motor vehicle accident, 1 in 103 that's huge.

    14:51 The lifetime chance of getting struck by lightning 1 in 15,300 and 10% of those die.

    14:56 So, one is absolutely going to be encountering a lot of vaccine hesitancy, due to the side effects, but the risks of death from COVID-19 itself, are far greater, than any theoretical risk from vaccine and one can also use these lifetime risks as well.

    15:13 So, how long will the protective effect last? Well, that's not known, in fact there are many questions that emerge, as we go further into the pandemic and here are some of the ones to which we don't yet have answers.

    15:26 It appears, that vaccine recipients in the vaccine trials, have had protective immune response, for a minimum of one year after vaccine, but that number will continue to lengthen as we go further into the pandemic.

    15:40 Can the vaccines prevent asymptomatic infection or can they prevent transmission? The tentative answer so far is, yes, but how successfully remains to be determined.

    15:53 Will they prevent infection by all the current or emergent strains? To date, the answer is, yes, but would decrease efficacy compared to the original strain.

    16:02 Will they be effective in immunocompromised patients? Here the data would suggest that immunocompromised patients are not all created equal, those who are on immunomodulatory drugs for example, somebody with systemic lupus or erythematosus or rheumatoid arthritis on a biologic agent, still have a robust response, while a solid organ transplant recipient or a chemotherapy recipient does not, so, it's a variable response and there may be a need for booster in those patients.

    16:34 Will the vaccines be effective in patients, who are at high risk for severe COVID-19 as those who are at low risk? Again, the answer would suggest, yes, but this is a smaller more difficult to study population, because of complications from those same comorbidities, which, already lend to morbidity and mortality.

    16:54 So, what are the major concerns with vaccine strategies? Perhaps, the hugest one is getting vaccines delivered, to as many people in the world as is possible and of course, there are many countries that are horribly under-resourced and either have no vaccine doses whatsoever or have been able to immunize less than 1% of that country's population.

    17:19 So, making vaccines available to all countries, all people in the world, as soon as possible is a critical concern, if we have and wish to have any chance of getting through this pandemic.

    17:31 Protecting those who are at highest risk for severe disease or those for whom the risk of infection is significant.

    17:38 So, protecting healthcare workers, so, that we can continue to care for those who do have COVID-19.

    17:44 Protecting the elderly, the ones who are at highest risk of hospitalization and death and including those who have immunodeficiency and then represent a huge burden in healthcare infrastructure.

    17:57 What about the variance? So, following the impact of the mutant variants of the virus and adapting our vaccine strategies to reflect those, all these are our major concerns and especially the duration of immunity.

    18:13 How do we detect if the vaccines are successful and for how long? Is it simply checking antibodies? or should we look at T-cell function, should we look at plasma cell derivations populations and lineages of COVID-19 effective plasma cells or neutralizing antibodies, versus other antibodies.

    18:33 So, there are a whole bunch of concerns which remain to be fleshed out.

    18:39 And then finally, limiting the insertion of the actual SARS-Coronavirus II, into the viral milieu of humans in an endemic matter.

    18:48 What does this mean? At some point in time, way, way, way, back when influenza was also a pandemic, however, it was so successful, that it entered human infectious milieu and now creates an annual epidemic.

    19:02 The fears are that our point of no return for, SARS-Coronavirus II has already been crossed and that we will likely have seasonal recurrences, just like we do with influenza, which, will require an annual booster vaccine.

    19:16 That is absolutely, I think a likely reality, if not already a true reality.

    19:22 And then what are the long-term complications of the disease? For example, those individuals who are long COVID-19 survivors, the long haulers as they've been called, which has horrible and tremendous impact on quality of life, can those be prevented by COVID-19 vaccination and can those be addressed as we bring this pandemic under control? So, lots yet to be determined, the science of course is evolving at a rapid pace in this pandemic and that is a good thing, because otherwise nature in its abhorrence of a vacuum, will continue to win, in creating variance, which, will eventually be the death of us.

    About the Lecture

    The lecture COVID-19: Vaccines by Sean Elliott, MD is from the course Coronavirus.

    Included Quiz Questions

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    1. A nanoparticle-encapsulated lipid that includes mRNA specifically for the SARS-CoV-2 spike protein gene is injected into the host to produce an immune response.
    2. Inactive viral mRNA triggers an immune response so that T and B cells are already activated in case of exposure to a new virus.
    3. The mRNA of a non-replicating adenovirus is injected into the vaccine recipient.
    4. Viral mRNA from the SARS-CoV-2 virus is injected, causing an immune memory response to recognize and fight off future infection.
    5. A synthetic nanoparticle already coated with the spike protein is injected into the host to produce an immune response to future SARS-CoV-2 mRNA, if exposed.

    Author of lecture COVID-19: Vaccines

     Sean Elliott, MD

    Sean Elliott, MD

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