Viruses, Pandemics and Immunity - with Arup K Chakraborty and Andrey S Shaw

[Music] we thought it might be good to start by saying what motivated us to write this book this human story really cannot be told without also describing the story of infectious disease causing microbes and pandemics past but because of improved sanitation antibiotics vaccines and good luck we the inhabitants of the 21st century have forgotten about the enormous economic and human toll that infectious disease-causing pathogens can exact so when proven 19 hit many of us did not have the concepts or facts that have suddenly become so pertinent and although there was a deluge of information the information was usually provided in snippets and not developed layer by layer in terms of concepts so that one could have a holistic perspective so we thought that if we wrote a short book which described these concepts then readers would be armed with the knowledge to not only understand issues pertinent to covet 19 but potential pandemics of the future and most importantly they would become informed participants in the debates that will hopefully now ensue about how we might build a more pandemic resilient world so today we're going to give a brief outline of some of the topics that we cover in our book and in our book as we develop these concepts we also inter-read stories of the people behind the science whose passion and dedication led to advances that enabled for example the development of these covet 19 vaccines at such a fast rate in describing the various concepts the drawings that we will use to illustrate these ideas are very much informally drawn in the style of our book and they are all the creation of philip stork who is a scientist at oregon science and health university as mentioned the written record since antiquity is replete with references to contagion in particular the great plagues and smallpox now our ancestors noticed that people who had recovered from disease could safely serve as caregivers people in china and india then started to harness this observation to protect against smallpox in a process called variolation iran material from the scabs of smallpox patients were collected stored and then administered mary wortley montague in the 18th century brought this process of violation to the uk and it's a remarkable story which led to the first formal vaccine trials if you clinical trials if you like which were organized by caroline the princess of wales but you know variation was a dangerous procedure and killed some people and led to localized outbreaks so we had to wait until jenner before we had a safe and effective way of protecting against smallpox jenner discovered that you could inoculate people with cow pox for relatively harmless pathogen and that would confer protection against smallpox and this discovery ultimately led to eradication of the scourge from the planet but jenner did not know that infectious diseases are caused by microbial pathogens that had to wait until the 19th century when pasture and coke and several others began to observe microbes isolate them grow them study their properties and thus came a new era in vaccine development for example pasteur had the surrender bitters observation that you could inoculate people with dead inactivated or attenuated pathogens and that would confer protection this was a major paradigm shift in vaccination the 20th century saw its share of pandemics too the 1918 influenza pandemics was partly responsible for for ending the first world war polio epidemics which ultimately led to vaccines by salk and sabin and then the hiv pandemic which still rages on today with antiviral therapies we can control it but we don't have either cure or a vaccine for hiv in the 21st century we have seen three disease pandemics caused by the same family of pathogens namely coronaviruses now when pasture was trying to make a vaccine against rabies he could not isolate and observe the causative agent because viruses which are such a threat to human life are tiny particles about 1 000 thickness of the human hair and so cannot be observed using a standard microscope now when a virus enters our body it then tries to invade our own cells viruses have spikes on their surface made up of proteins and for example sar cov2 the virus that causes covid19 its spikes bind to a protein a molecule on our cells called ace2 which helps regulate blood pressure now ace2 is abundantly present on cells in the lung blood vessels those that cells that help us smell heart kidney etc and so this virus can infect tissues in the in various organs and cause potential complications in very many different organ systems now once the virus binds to ace2 through its spike it still has to force its way into the cell and sar cov2 collapse one of our own cellular molecules which acts like a scissor and cuts the spike into two which is like releasing a spring which then injects the viral materials inside our cell and now the virus has to replicate that it has to make many copies of its proteins and then start to assemble many different virus particles which then can go on to infect other cells now how does the virus make many copies of its proteins to see that let us first have a reminder of how we make many copies of our proteins now a cell is the quantum if you wish of a functional unit in us and if you think of the cell as a car the various proteins are its parts and so the cell has to make many many proteins in order to function and information about the proteins that we can make is encoded in dna which sits in the nucleus of our cells as you know dna is a helical molecule made up of two strands each strand is made up of four units or bases called t a c and g and the reason it forms a helix as the two strands wind around is because t only binds to a and c only binds to g so one strand is the complement of the other the way that dna encodes information about our proteins is the following proteins are made up of amino acids we have 20 types of amino acids and triplets of these letters on dna code for different amino acids so for example acg codes for amino acid 1 gcc for amino acid 2 and so forth so how is the information contained in this dna result in the production of proteins well the dna strand is a sequence of letters as we said and we have a molecule called rna polymerase then uses this dna strand as a template and makes another molecule an ancient molecule called rna and it also is made up of four letters except that t becomes a u so this rna that is made and many copies of it are made this way contains the same information as the dna and then this information is translated into protein production by a huge protein machine in us called the ribosome so this set of steps dna to rna to protein is called the central dogma now viruses come in broadly two categories dna viruses and rna viruses now dna viruses carry the information about their proteins in the form of dna and herpes viruses chickenpox viruses are examples rna viruses carry information about their proteins in the form of rna the chronoviruses and influenza viruses or examples now viruses however cannot translate the information contained in their dna or rna into proteins and multiply on their own they need to infect plants animals or us and then hijack our cells machinery to make their proteins then begin to multiply viruses if you like are like very experienced travelers who travel light with only the things that they know they cannot find in hotels namely our own cells now dna viruses their this information is translated into their proteins rapidly by our cells machinery as per the central dogma that i just described however rna viruses break these rules rna viruses like coronaviruses have bring a molecule with them called rna-dependent rna polymerase and what this does is that it copies this rna into many other copies of rna very rapidly and then our ribosome takes these rnas and makes them into viral proteins and therefore many viral particles hiv is a class of virus called retroviruses and they are even more weird what they do is they first take their rna and using a molecule they bring called reverse transcriptase they convert this to dna and then this piece of dna is inserted into our own genome and then as per the central dogma our machinery converts this dna into rna and then to proteins now one of the surprises that was there when we sequenced the human genome is to find the significant fraction was composed of ancient retroviral genes that were silent apparently we've been doing battle with retroviruses for a very long time so the viral replication cycle for a rna virus is that it enters then it makes many copies of its rna which is made into proteins virus particles are assembled they put out of this cell and then go on to infect other cells and people antiviral therapies like rem deservier for example try to block one or more of these steps of replication during the viral replication cycle now as you mentioned we've been dealing with viruses for ever because they are very ancient organisms but the viruses that infected our ancestors were probably both different in type and diversity compared to those that prevailed today many of the viruses that circulate today like influenza and coronaviruses are spread across the population by casual contact between people now some do die because of the equity of the acuity of disease but for most of us our immune system vanquishes the virus a memory of this infection is then imprinted on our immune system and if we are infected again our immune system swats this virus away viruses like this would have a very low probability of thriving in pre-agrarian times our ancestors then lived in small communities and spread over very large tracts of land the low density of population so most people encounter very few others in their daily lives and so if they were infected they would infect only a few other people if the virus was highly lethal it would kill this small community and then it would not be able to replicate anymore and that would be the end of that viral species if on the other hand our immune system was able to vanquish the virus very few people would remain susceptible very quickly and that again would be the end of that viral species that is it would go extinct our ancestors were likely not afflicted by viruses that were terribly contagious or deadly or ones that our immune system could readily vanquish rather they would adapt to live within us silently most of the time but once in a while they would rear the heads and start to multiply our immune system would suppress them and this cycle would go on dna viruses like herpes viruses are examples of such ancient viruses that circulate in the human population today all of this changed when our ancestors learned how to grow crops then we started living in larger communities the population density became higher and so one person could transmit the virus to many others in a large dense population new birds and trading with communities nearby provided a steady stream of newly susceptible people we also started to domesticate animals and so viruses that were living in animals in the past started to infect humans all of these effects were enhanced with the growth of the population the industrial revolution and urbanization and travel so here is a map of uh when the human population was 256 million people in thousand a.d and you can see what the population density looked like the population exploded to 6.4 billion in 2000 but what is important to note is how densely various areas were populated and how we started to populate completely new areas which brought us in proximity with completely new animals thus it was that a great diversity of viruses started circulating humans which could be spread by casual contact how did these viruses start to cause pandemics well the processes by which viruses like the coronavirus or the retroviruses like hiv make many copies of their proteins are error-prone so for example in the case of these sorts of coronavirus-like vaccines a mistake could be made while copying it such that this u would become a g and the same is true for these retroviruses which can also make errors now a different rna means the corresponding proteins are different and so this causes the emergence of viral mutant strains now most of these mutant viruses are worthless and they they they're not functional but sometimes a functional virus that is mutated can emerge and sometimes they can become even more functional than their parents and that is what happened for example in this viral strain of sar cov2 that was first identified in the uk which became more transmittable and therefore started to take over the population now viruses can also change guys in other ways for example imagine a virus like the coronavirus and it is in fact two different strains of it in fact the same cell in a particular animal so this could be two strains that are one coming from a human one coming from an animal or it could be two different viruses that live one from one animal and the other from another animal or for organisms like bats which harbor many types of coronaviruses for example it could be two viruses in the same same animal now what happens then is that this rna polymerase starts to copy this red rna and then hops off and then starts to copy the green blue one and so you can get hybrid viruses with a combination of these genomes by this process called recombination in other viruses such as influenza the rna genome actually comes in segments that is to say these are like cassettes that are interchangeable so once two such viral strains infect the same cell what can happen is hybrid viruses can arise which are made up of a mixture of cassettes some from this guy and some from the blue virus this process is called reassortment now if a virus is circulating in an animal species this virus adapts to thrive in this animal and so because we are different they're most likely not going to be able to infect us or cause any trouble but because of this malleability of rna virus genomes through processes of mutation recombination and reassortment sometimes in an animal a virus can emerge that becomes able to infect humans alternatively it can become able to infect another animal and then other mutations could occur while it adapts to this animal and if this animal is sort of like us then that could also that virus could also become capable of infecting us sars mers sar cov2 and the influenza viruses that cause pandemics undoubtedly arose in this way and when such a new virus emerges no one in the population has immunity to it and so if the virus is reasonably contagious and can be spread rapidly and it's reasonably lethal it can cause a frightening pandemic such as the cobit-19 pandemic now even though we have been living with viruses for so long uh we've been winning these wars or at least the battles and we'll win the kobet 19 battle as well and that is because we have an immune system that can combat these pathogens and we have learned how to harness this immune system to create vaccines and andre will now describe these important topics so the ability of the human race to survive has been dependent on having an immune system that can adapt and specifically recognize and obliterate all of these new pathogens immunologists over the last hundred years studying the immune system have recognized now that we've got two parts of our immune system we have the adaptive immune system that many of us are familiar with this is part of the immune system that makes antibodies and makes t cells and these weapons antibodies and t cells are generated in a bespoke fashion they're generated to be specific to every pathogen that they see but part of the problem of having a system that is this powerful and this specific is it takes time to generate these specific weapons against the virus and so we think now that the adaptive immune system takes about five to seven days to basically kick in if we were to only rely on the adaptive immune system most of us would be dead before by the pathogen before the adaptive immune system could come to the rescue and so we've recognized is that we have an innate immune system that functions to alert the body that a pathogen is entered and it uses some very broad mechanisms to slow down the growth of the virus or the or the pathogen the tools of the innate immune system are relatively blunt they're kind of a one-size-fits-all sort of system the innate immune system has specific receptors that recognize that a virus or a bacteria or a fungus has entered the body when it senses their presence it triggers a system-wide response releasing hormones that immunologists call cytokines that cause symptoms like fever like muscle ache like fatigue like lack of appetite these cytokines also change your metabolism they change your blood flow they increase clotting when you start to feel sick it's because the innate immune system is kicked in it's functioning not only to slow the growth of the virus but it's also telling the adaptive immune system that it needs to start working on a specific response now one of the most important differences between the innate and adaptive immune system is the concept of memory the innate immune system has no memory every time you get infected it has to do the same thing but the adaptive immune system actually remembers which viruses that you've been infected with with bacteria you've been infected with so the next time you're infected with uh the same pathogen it kicks in very quickly very efficiently and most of the time you never even know you were infected by that pathogen so putting this into context probably the easiest way to think about how the innate and adaptive immune system works is to really think about covid so when you get infected with covid you're exposed to the virus virus enters your body and begins to grow at a certain point the amount of virus that's growing your body reaches a point where the adapt where the innate immune system is able to recognize it and that's when you become sick the activation of the innate immune system is triggering the adaptive immune system to go but as i said that takes about another week before it's able to be ready to fight the virus as viral levels arise the adaptive immune system makes you feel sick but eventually the innate immune system makes you feel sick but eventually the adaptive immune system will kick in and the adaptive immune system is very efficient at getting rid of the pathogen and so pathogen levels will fall your innate immune system is no longer triggered to stay on so the patient feels better and eventually the adaptive immune system completely clears the pathogen from the body now one of the weird mysteries of the covid19 virus is that there seems to be a delay in the triggering of the innate immune system this gives the virus a couple of extra days to grow increase in volume making it a little bit harder for the adaptive immune system to actually clear the virus but this explains why patients who get infected with covid often feel well but have enough virus to infect others before they start feeling sick now in the cases of severe illnesses the adaptive immune system is unable to completely eliminate the virus and when this happens virus levels are staying high the innate immune system cannot turn off and then patients begin to feel worse and worse this is probably due to higher viral lows that make it harder for the adaptive immune system to clear this has cascading effects on the health of the patient because the adapt the innate immune system was not designed to be on for weeks at a time and because the innate immune system cannot turn off this is very detrimental to the health of the patient and this is generally the time at which patients are feeling very badly they're doing very poorly and they become hospitalized and some of them are sent to the intensive care units the strategy behind our medical treatments like steroids like specialized drugs that basically dampen the effects of the immune system and covalent antibodies are really there to help support the patient to decrease the viral load and hopefully buy time for the adaptive immune system which we hope at some point is going to kick in and then clear and sterilize the body from the virus so how does the adaptive immune system work as we've told you viruses come into the body they bind to cells they enter those cells the viral nucleic acids make viral proteins they assemble new viruses that are then released into the bloodstream the adaptive immune system has two different cells called b cells and t cells now b cells are the cells that make antibodies we have over 10 billion different b cells that are able to make 10 billion different antibodies and so when a new virus enters the body it is exposed to all of these different b cells and hopefully you have a few b cells that are able to recognize the virus and when the virus binds to the antibody molecules that are on the surface of the b cell the b cell begins to proliferate and the proliferating b cells will also make antibodies that go out into the blood and these antibodies will bind to the virus and block the virus from entering what we describe in the book is that this is a little bit more complex process it's a darwinian process and we have a system that allows us to generate the most highly efficient antibodies now we need t cells to basically destroy virally infected cells because antibodies cannot destroy the viruses that are within cells and so the cells that are making the virus need a separate way of getting destroyed and that's through the t cell system now what t cells are recognizing are small fragments of viral proteins that are transported to the surface of cells and basically displayed on the surface as flags to tell the t-cell system that i'm infected with a virus and i need somebody to come in here and kill me so just like the b cells we've got over 10 billion different kinds of t cells allowing t cells to see a vast diversity of different peptide molecules and when a t cell sees a specific peptide molecule that it is specific for it like the b cell will proliferate but this time the t cell actually will differentiate will basically convert into specialized cells that are specific to getting rid of the virus one of these cells is called a killer t cell or cytolytic t cell it basically can travel around the body and when it recognizes an infected cell this cytolytic t cell can go in and destroy it now when the infection is over we don't need all these b cells and t cells anymore and so for the most part most of the b cells and t cells that we've generated in immune response are destroyed but importantly we keep a few of these around and that's what memory is we want a few of these around so that the next time we see the virus we have more of these cells they've already been selected for their great properties and so they can be activated very quickly they don't need a weak they can be activated very quickly and most of the time as we've said you never even know you have the second virus because the b cells and t cells ready to go basically destroyed the virus before it could really take hold in the body or even stimulate the innate immune system but this memory this ability of the adaptive immune system to have memory is really the basis for vaccination so as we describe in the book vaccines and vaccination we've been using this next slide we've been using vaccines since the time of jenner to generate an immune response uh against pathogens and as arupa is described in the 18th and 19th century pasteur and robert koch in germany who were hotly competitive with each other uh recognized that the generation of vaccines was going to be a very efficient way to protect humans from the miseries of infectious diseases and they came up with two strategies one strategy was just to collect the pathogen grow it up and kill it and then use that killed pathogen to immunize and vaccinate individuals and and probably the most common example of a vaccine of this type is the influenza vaccine this is what we do every year we pick a certain strain of influenza it's grown up it's killed it's given to massive numbers of people pastor also came up with this live attenuated vaccine this is the vaccine that he came up with for polio what he did was he tried to grow a virus that didn't cause disease but would generate immunity to the to the pathogen very much like what jenner was doing with smallpox and this is how he generated the rabies vaccine and for most of us the most common live attenuated vaccine that we're familiar with is the measles mumps and rubella vaccine that all children get and as we'll go over in a minute the polio vaccine by sabin is an example of a live attenuated vaccine and the salk vaccine is an example of an inactivated now the great accomplishment of vaccine development in the 20th century was the subunit vaccine prior to this we needed to grow up bacteria kill it inject it into your body or grow up a virus kill it inject it into your body and so people really wanted to figure out a way where we can vaccinate without giving you the whole organism and so the realization was the nucleic acid in these pathogens make proteins and so if we could just synthesize the specific proteins in the laboratory mass produce them we could use these purified proteins as the basis of the vaccine and this way we would eliminate ever having to touch any of these infectious organisms we wouldn't have to think about uh injecting them into humans and this is the basis of most of our vaccines today and the ones that you're probably familiar with are hepatitis b the human papilloma virus and for many of us diphtheria pertussis toxin and tetanoids tetanus toxoid is a common example of a subunit vaccine covid19 ebola sars and mers has really helped push the development of new technologies uh and so we're hearing a lot about these today probably in the first category of vaccines to be approved are the rna vaccines the ones made by bile intec and pfizer and the modernity groups both of these vaccines mass produce the rna that encodes the proteins of the covid19 virus this rna then is formulated into a vaccine that's injected into individuals cells of the body take up the rna they use this rna to basically make the copin 19 proteins and now you get an adaptive immune response to those proteins the newer viruses that are beginning to come on the market now one was developed at oxford and then licensed to astrazeneca the other one was developed at harvard and licensed to johnson and johnson basically use a benign cold virus that doesn't normally cause disease these viruses are engineered to carry the dna for the covid19 proteins when these viruses are injected into humans they infect cells the dna makes rna the rna makes the covet proteins and now you have an immune response to the covate19 proteins and hopefully these will generate a good adaptive immune response and memory i should mention that these viruses are also engineered so that they are unable to replicate once they enter the human body so they are completely safe now one of the pleasures of writing this book was to learn about the incredible story of the polio vaccine i for one i knew about salk and sabin but i hadn't appreciate that this story is one of the greatest scientific triumphs of the 20th century and i think in telling it it really illustrates many of the issues that we're talking about today in the development of the covet 19 vaccines now there's very little evidence in the historical record until the late 19th century for any cases of polio we first became aware of polio in the 1860s when small epidemics of polio that was were resulting in childhood paralysis began to be reported uh sporadically in the late 19th century mainly in scandinavia and and in the united states these epidemics started to grow both in frequency and in size throughout the beginning of the 20th century by the 1940s in the united states polio was causing about 21 000 deaths per year of young children and so there was a great desire to understand what was going on was this a new virus or an old virus we know from looking at the archaeological record that egyptians described potentially an infectious disease that was causing a paralytic disease that could have been polio what we think today is that polio is ancient that prior to the 20th century most children were being infected with polio during infancy and were likely in fact uh being protected by breast milk children exposed what we realize now is that children exposed to polio at older ages have less protection from it and the virus had an increased propensity to spread and infect the nervous system and this was causing paralysis we believe that the increased hygiene of modern societies was causing a delay in childhood exposure to polio explaining while paralytic polio cases were increasing mainly in developed countries and understandably there was great fear for children in the summer months and this resulted through the 20s 30s and 40s in the closure of beaches swimming pools movie theaters and other activities that involved young children the infection of franklin del delano roosevelt at the age of 39 in the early 1920s was a galvanizing moment and he started a charity called the march of dimes to develop a vaccine so the first breakthrough in polio was the work of john enders at harvard in 1949 where he figured out how to grow the vaccine or how to grow the polio virus jonas salk immediately recognized that this was going to be the path to making a vaccine and so in three short years jonas salk working as an academic physician at the university of pittsburgh figured out how to massively grow the virus how to inactivate it with certain chemicals and formulate it as a vaccine to give to children in 1953 four years after john enders had figured out how to grow the virus jonas salk started safety trials testing the vaccine to make sure it didn't hurt anybody and even he even treated his own family in 1954 he announced that he was ready for large clinical trials and because epidemics occurred mainly in the summer what they wanted to do in the 1950s between 1953 and 1954 was to immunize a significantly large number of children mainly seven-year-old children and get all of this vaccination done before the end of the school year in may this was complicated by some of the regiments requiring up to four or five booster shots and there were controversies like we have today about the ethics of such a trial and whether we should use placebo controls eventually a variety of trial designs were used and almost 2 million children in the united states and canada participated in these trials after the summer ended they had to tabulate all the information and given the huge size of this trial and the massive amounts of data in this pre-computer age it took almost nine months to come to the conclusion which was announced in the spring of 1955 that the salk vaccine was successful now albert saban was another polio scientist who was about 10 years older than sulk and he had been working on polio since the early 1930s he had a pretty good track record in the field as he was the one who identified that polio was spread by contaminated water and food and that it first infected the gastrointestinal tract and this led him to believe that the best vaccine for polio would be one that we could swallow and infect and protect the gastrointestinal tract from the polio infection he spent the 30s and 40s developing a weakened attenuated strain of polio that didn't cause disease that he could give by mouth but by the time he was ready in 1954 and 1955 the march of dimes and the u.s

authorities were unwilling to help him test his vaccine because they felt that we already had a good vaccine in the salt vaccine and there was no need to have a second vaccine so saban actu uh went to the russians who mass-produced the vaccine and tested it on up to a hundred million individuals and i i find this story remarkable because this was happening at the height of the cold war the sabine vaccine was approved in 1961 and it turned out that saban vaccine was much easier to produce did not require syringes for injection and so it was very easy to use in max mass vaccination campaigns the saben vaccine also only required a single dose and unlike the salt vaccine conferred lifelong immunity it's mainly through the use of the savin vaccine that we've eradicated polio in almost all parts of the world however the saben vaccine because it is a live virus does result in a small number of polio cases in a small fraction of the pay of the individuals who are given the vaccine and with this much lower incidence of polio in the world today the us and the uk decided about 20 years ago that it was time to go back to an inactivated vaccine which is much safer and and so that is the current vaccine that is used today i think this example shows how important it was to have more than one vaccine how differences in the dosing schedules how long the immunity lasts and how easy it is to administer are issues that are just as important as the efficacy of the virus we have much to learn about the effectiveness of the current covet vaccines and so it is really a good thing that we have multiple strategies going we have many new vaccines that are behind the astrazeneca and the jnj vaccines and so only time will tell what the best vaccine is for the human race thank you andre let me just uh end by making a few comments about how we might take steps to developing us technologies that might and the scientific discoveries associated with it that might lead to a more pandemic resilient world and i'll speak today only to two such technologies one of them concerns testing in many countries one of the big challenges when the pandemic first hit was that we simply could not deploy at scale widespread testing so that we could quarantine and isolate people in the early days of the pandemic this is not surprising when a new virus emerges and even now the typical paradigm for testing is a sample is collected sent to a laboratory and then results come back after some time what we really need for the future are portable reliable testing methods that can be used at the point of view care and deployed at scale and moreover can be easily adapted to screen for a new virus if one emerges several people are developing such technologies so this is not fantasy for example here is one such example created by collins and co-workers during the zika epidemic the sample is collected its rna is isolated and amplified by standard methods but then synthetic biology is an approach that allows you to make cells do what you want them to do not what they usually do and usually these cells are bacteria so these guys they made a synthetic biology circuit which can detect the rna from zika and then when it does so it secretes a chemical that has a particular color so this synthetic biology circuit was placed on top of a filter paper and then suddenly freeze-dried and so then you could transport it as a piece of paper anywhere you wanted and once you got to the point of use you added water and started to function so if you dropped a bit of the sample on it if it changed color to this magenta shade you are zika positive and otherwise not much like a pregnancy test these sorts of tests need to be developed and deployed at scale because they're also easily adaptable from one virus to another now today we hear a lot about the threat that could come from the new coronavirus strains that are emerging for example the south african strain that causes kuvin is not as efficaciously but thankfully still effectively inhibited by the current vaccines but now when the whole world is vaccinated there will be an enormous selection pressure on the sar cov2 virus population to evolve and mutate in ways that can evade this vaccine so perhaps it will become like the flu and we are already designing vaccines that can adapt to the new strains that we know about and so forth but can we think of a pan coronavirus vaccine one that would be effective for all coronal viruses including future ones that may emerge now this is not complete fantasy for example for different virus species hiv and influenza being two such examples much progress has already been made in creating these pan virus family vaccines although clear success is yet to be reported so this is a depiction of the spike of the hiv virus and while it has a highly variable regions there are regions like the ones shown in yellow here that are relatively conserved that is the same from one virus to the other for hiv similarly for influenza there is a similar region here and these regions are more or less the same because they are involved in the mechanisms that allow these viruses to infect human cells so now if you can design vaccines that attack with antibodies and t cells they attack these regions of the virus then those vaccines will be able to be effective across a virus family now by massively sequencing viruses and having a global surveillance program that includes sequencing animals that contain particular virus families and then taking that massive amount of data and using the power of modern machine learning and computational models and then combining that with the unprecedented amount of knowledge that we are gaining about the pathogenesis of viral infections and immune responses to this during the current pandemic we may be able to identify for virus families that are important such targets and design vaccination schemes that can elicit immune responses that target them and as andre mentioned the 21st century vaccines are easier to quickly make because both the rna viruses and the adenovirus vectors they do not contain the proteins of the virus but information about the proteins of the virus so they could be quickly made to take advantage of these advances such vaccines would take us some ways towards building a more pandemic resilient world there are many such technologies that need to be developed in scientific discoveries to be made so that the next time it doesn't have to be like hobit 19 again the question is whether we will make those investments so with that we'll stop and uh thank you very much for your attention you

2021-04-27 10:14

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