 Hello and welcome to NewsClick. Today we are doing our science show. We have guests on the show which I will introduce you to just a little later. Let us first look at what is the topic. The topic is how do you create a vaccine which can stop the various strains of SARS-CoV-2 what causes COVID-19 and is there the possibility of having a universal vaccine which will work on a number of different variants not only of SARS-CoV-2 but also maybe other similar infections of the SARS-CoV-2 family. So this is what is the discussion today. The possibility of a universal vaccine will show you first this is the SARS-CoV-2 spherical particle which is there on which the different kinds of proteins which are embedded on the surface of the SARS-CoV-2 virus. When it enters our bloodstream different antibodies try to latch on to different parts of it depending on the kind of antibody it is and therefore it triggers a response which leads to the destruction of the SARS-CoV-2 virus particle within our body. Now this identification of what works what doesn't work is the memory that the body has which is what gives rise to a vaccine. So there are different kinds of vaccine earlier we used to have what is called the you know a inactivated virus particle itself a dead virus particle or inactivated virus particle then we have genetic engineered virus vaccines which can slip off a part of the virus particle and then use that to generate the antibody vaccine antibody in the body which is what leads to the vaccines. But the problem that is there is what's called immune escape that the vaccines have to change continuously as the virus itself changes and this immune escape property of the virus is why we need to take flu virus vaccines every year particularly for old people like us we did a flu vaccine but it changes every year and that's exactly what we find with SARS-CoV-2 as well it changes very rapidly. The target is a universal vaccine and this is what a universal vaccine could look like that that you have this ball very small nano particle and which you embed various proteins. Now this then the proteins that we embed here the parts of the virus you embed here are what would be called the parts of the virus which don't change that much that means even with all the immune escape we see the different virus variants you've got these don't seem to change that much and you take those parts and embed them into this nano rubber ball equivalent as it was like a soccer ball actually and then this experiment was done again with the team which was in Caltech and they took eight what would be called the Sarboka coronavirus family out of which of course SARS-CoV-2 is one of the viruses within the took and then they tried to create this this vaccine quote-unquote particle which would have different proteins embedded on its surface and this was used to it was tried on different animals and what it was found is that it seems to be able to protect that animal from the infection. This is the quest for the universal vaccine is what we're going to talk about with our experts in the studio and the interesting part is that at least we now have something in the lab it must be understood it is not it has a long way to go before it becomes a vaccine but you've got something in the lab and an approach which seems to indicate yes there is possibility of a universal covid vaccine. Coming first to Gautam, Gautam what has prevented us from doing this till now is it the knowledge science that we didn't know enough is it the technology we didn't know how to do this or is it the money and the political will shall we say that we should spend on this as a major exercise so at least I think it's partly the technology first because the ability to do this sort of bioengineering that makes something of the sort that we'll describe this today the nanoparticle with things coming out to it that represent parts of the virus that's a fairly recent breakthrough and of course money I think the large sums of money that have to be devoted to development to testing and finally taking it to humans certainly been inhibited earlier and now with now that the world has understood the impact of SARS-CoV-2 that barrier at least is much reduced and governments are prepared to invest very large sums of money the private sector is prepared to invest very large sums of money in this. So essentially the quest for a universal vaccine didn't really start or wasn't thought of such in as a possibility because you feel because the technology was really not up to it at that point so Vinita you from the other side meaning that you know the viruses as well what would be your response to the possibilities that we had earlier we didn't explore them or we didn't really have the ability to explore them. I think it's both Gautam is partly right in the sense that there were technological hurdles the paper that we will be referring to again is is a technological breakthrough of sorts but it's not the case that we haven't tried this earlier for example polio oral polio vaccine was a combination of three four polio strains so again because they were somewhat different they the combination was required so is the case with developing and developing dengue vaccine which is in the trial phase different problems with both dengue and polio are different but this principle of mixing individually prepared vaccines together so that at least hurdles of giving four injections or four oral doses is overcome by giving one single dose but technology to integrate all of this together by synthetic biology wasn't there as much as what we are seeing even today I'm sure there are difficulties. A part of it Satyajit is also that I unlike the case of polio say or certain other diseases where the this kind of change we seem to see in SARS-CoV-2 or in the flu virus that doesn't seem to be that much but in these cases these seem to change very rapidly is that also what makes the possibility of say the equivalent the polio vaccine much more difficult for flu as well as for COVID. So I'm going to disagree with both Gautam and Vinita that is the good part of it having three of you here so we get an actual discussion. Let me start with my agreements. Vinita is right of course we've been trying to make multiple strain specific vaccine formulations in a variety of infectious diseases for a long time with variable degrees of success polio has been a qualified but respectable success many others not so much and both she and Gautam are right that the recent technological report from a few months ago from Pamela Bjorkman's group is an interesting bioengineering trick for getting a certain kind of preferential immune response but I think that we are missing the elephant in the room in all of this and the elephant in the room is has got four legs one that all of this works if well if you know what the variant strains are it doesn't hold up particularly well if you don't know the strains now both my friends are going to point out that the Bjorkman paper actually tests for a couple of strains that were not included in the formulation that they tested and they still got immune response against it but those are all very closely related strains what will happen over six months or a year of maturation of virus evolution is entirely unknown the second leg is that the kind of antibody response that you want to get a so-called cross-strain specific protection is our imagination once we put that sort of pressure immune pressure onto a virus population it would not at all be surprising to begin to find virus variance emerging let's sidestep that kind of protection it's one of the extraordinary abilities of proliferating life and natural selection that this happens let me stop on two legs since my friends will want to respond to those before I get on to the elephant's hind legs they're going to get some hind legs here finally also but I think it's really too of you to respond to what you said my question also is one of the questions I had was are certain say parts of the virus shall we say in my layman's language are less variant to change a more conserved as it were and therefore a vaccine target there might be much more successful is that the argument so that's the argument that the paper makes that you can isolate parts of the virus that mutate less that are more conserved and isolate them and attach them to this nanoparticle so let me just describe what what the methodology of the paper is that's to make a roughly spherical nanoparticle with little legs that come out that are sticky legs to which you can attach parts of the virus you can attach multiple parts of the same virus or you can attach parts of different viruses or different variants of the same underlying virus in this particular case you can choose those parts such that they represent more conserved parts of the virus that don't change much through viral evolution so that's where I disagree a little bit with what Satjit says it's possible to do this a better job than a completely naive job by isolating those parts that don't change very much and there lies the hope for having a sort of pan coronavirus or pan sarbeco virus vaccine in that particular case so I don't think the situation is as bad as that certainly there will be mutations certainly there will be changes and there will be escape from the sort of pressures that are imposed by the vaccine but one may hope that it will last substantially longer than the short period if you only looked at those parts that change very rapidly well that's an interesting of course question which only future will answer we haven't still come to Satjit's hind legs so Vinita what would be your response to the elephants two front leg question that Satjit has posed to both of you I don't think he particularly contradicted what I had said he added his own leg to it so that's all right but what I was in fact thinking of was his argument is right that in this particular case the points the antigens or the parts which which have to be inserted into the nanoparticle one has to know them in advance so that there with there is going to be utility for this and in a sense it's it's one will never essentially win the race in a manner of speaking if the virus is capable of mutating very effectively like flu virus is or the coronaviruses are so in that sense what he was saying is correct but I probably would go I don't know what his third and fourth legs talk about but I was in fact thinking that this is a strategy that in principle it can be used even for unrelated virus what Gautam was referring to why do we have to predict that there will be sarbicoviruses which is what has been used here to make the mosaic particles that you use six or eight different subsets and then you have more protection for four additional subsets of the virus or strains of the virus instead of that can one actually simply use the way polio virus is designed which is what I was referring to that either you in insert relevant parts of the polio virus or relevant parts of Japanese encephalitis virus or together I mean all we need is decreasing the frequency of immunization if the vaccine is effective it's going to provide protective responses and long lasting responses all of this is not really tested for the in the paper but all I'm saying is that the strategy can be expanded and one doesn't have to necessarily look for sarbicoviruses variants as they will emerge in the future well the argument should be even it gives you a longer lasting vaccine than what we have now because this this particular one the covid 19 as well as the flu this seems to be particularly adept at changing and defeating the vaccines we have so that we have to have the next generation next year's vaccines for the indexes and kind of thing so Satyajit responding to these two is only a small part of what I expect you to do I really want you to go also on the two other legs that you are threatening to I will not say kick us with but nevertheless put this put it up to us so so let me start that by pointing out the really interesting bioengineering biological trick involved in what Bjorkman and her colleagues have done Gautam points out that they're taking little nano balls and they are spacing sticky bits on these nanoballs what they are then doing is putting complementary velcro sticky bits of virus onto these nanoballs in such a mixture that no two neighboring sticking bits on any given nanoball are the same variation and because the immune response likes to bind to more than one site at a time in order to make a good response the hope that Bjorkman and her colleagues had which seems to have been realized in a controlled situation is that only those antibody making cells whose antibodies can recognize multiple variants will be most efficiently triggered this is really the heart of the Bjorkman trick it's also the reason why the technology is particularly of interest for a virus family with multiple minor but consequential variations I'm not suggesting that Vinita's point is not valid of course it's a technology that can be used much more broadly but this particular angle makes it very attractive for generating what is called cross protective across minor variations strain protective antipaxene immunity that brings me to my two hind legs of the elephant in the room which is the first of which is that these responses means that the cell that is responding to this nanoparticle is not actually binding to the nanoparticle with uniform binding potency because different parts of it are binding to different targets and therefore the potency of binding to different targets is variable it is quite possible that as a consequence not just the magnitude of the antibody response that will result but more importantly the duration of the antibody response that will result might be handicapped in consequence this is this sort of stuff in with some caveats has happened in experimental immune situations in the past so it is a genuine worry as the third leg but the fourth leg of the elephant is to do with real life situations in communities which is all of this we are talking about when we immunize an animal with the this combination of SARS-CoV-2 variant targets the animal has never seen any such target at all so far and therefore the cells in the animal that are responding to this engineered target we hope are strain cross-protective cells what happens as with the real life situation of SARS-CoV-2 and COVID-19 where the bulk of us are either vaccinated and pretty much universally infected in the past with one or two or maybe at most three strains with all the expanded antibody making memory cells in us that recognize those one or two targets with high efficiency that then becomes an enormous problem for this entire Bjorkman model the model works beautifully in controlled laboratory situations whether it will do so in the far messier real life situation I think is the real elephant in the room well I think we have covered a lot of ground I have not come to the trunk of the elephant which I am inclined to at the moment that if all this succeeds and succeeds so well that we eradicate most of the diseases like smallpox will it happen that the therefore the vaccines will vaccine making will stop and be equally unprepared in the future a completely thought experiment now I don't think that's likely that we've seen I think that 80 percent or 70 to 80 percent of all new infections or novel viruses come to us from zoonotic sources from animal sources hope yet perpetual sources for sort of new things to happen over there you say hope yet for new diseases yes and new vaccines any closing thoughts with it and Satyajit to anything that has been discussed or you know you want to put further into the room Satyajit please bear with our audience they don't understand a lot of the stuff that you say and you throw out so try if you if you can leave the science out or make it a little more such that we can understand it might be easier for us you know unfortunately we are not well equipped to handle particularly the biological sciences the most complex of all the sciences that we have Benita first yeah well I know Satyajit what Satyajit described as a forklift it's a very technical point but it is completely something one that I accept and concur with what he's saying what he had said but about the generalities I agree with Gautam that uh with with time our numbers are going up our as in human beings numbers are going up jungle and environmental protection which needs to be there is not there there are multiple many more chances with the time that they're the zoonotic viruses that means those which are primarily the diseases of the non-human animals but they jump into the human beings the ways our scope is supposed to have happened so that those are the likelihoods that we will have to live with so in a sense need for new vaccines is something that is going to stay I don't know for how long certainly be much beyond our lifetimes since all of us here are looking quite elderly to me so including myself so I don't think the the end of that effort is anywhere inside and also I I think the while we discuss the technology the current technology that we were discussing of this mosaic particle which was which is being uh in uh interestingly developed I suspect even for that technology to be to become feasible for me in uh for the companies pharmaceutical companies or vaccine manufacturing companies so that mass production is possible is still very far away so this currently what we are talking about is excitement and going up and down jumping up and down essentially thinking oh wow this is something interesting this is something new whether it will reach ultimately multiple hurdles that it still has to cross it's very hard to say so Tijit the wise words of the sage um I don't know about that but let me make three very quick points firstly is this a cool new trick absolutely yes it is just truly cool new trick is it going to solve the vaccine problem no it's not um vaccine problems are multi-layered and multi-dimensional and this is this is a really interesting instrument but it's not going to solve all our vaccine problems um it's going to be interesting in a specific sector of vaccines however let me end with my third point which is when are the poor people of the world going to see this new technology and how are they going to see it um the um clinical trials that are starting off the ottmann's vaccine are of course um entrepreneurial companies um what the intellectual property rights are is anybody's guess at this point but given what we have seen over the past three years with the mRNA technology um I'm left skeptical about the speed with which technologies of this sort can achieve two outcomes of interest to society firstly to actually reach people in need as vaccines and secondly to reach poor economies in an effort at techno commercial decentralization across the world of societal commons and it underlines a point that keeps coming up over and over again over the past three years with the mRNA technology which is our response for ensuring social justice in these matters of biotechnology should not be technology specific because here is an entirely new technology about which different questions from our mRNA technology are going to come up and we are going to need to address those just as much as we need cross protective vaccines we need cross protection for social justice and access with biotechnology I think that's a very point you're raising which we didn't have time today to discuss which we need to address at some point hopefully sooner lot rather than later if there is some success on this but it's interesting that you raised that because this is being funded the clinical trials have been funded by SAP and as you know that's a Bill Gates foundation and I mean behind it and they seem to hold a lot of influence on that area and they believe in patents and commercialization through companies rather than it becoming a public good so we will leave it at that and let us hope that at least the science and technology of it succeeds so that we can fight the bigger social and economic battle on that thank you very much to have you with us really today it's good that we have had Gotham with us in the studio otherwise normally these discussions given the sparsity of shall we say scientific and tech people in this world at least on accessible to us that we really get really rarely get to see people in the studio and of course Satyajandrita both of you who have been with me on a lot of these discussions particularly Satyajit trying to talk about COVID-19 and all the issues there and unfortunately for us those issues are not going away soon this is all the time we have for news clicks science show this week and we'll come back to you with more such issues in the future