 Hello and welcome to Newsclick. Today we're going to discuss the vaccine trials that are underway and how positive or how long do we have to wait for a vaccine. Both these questions are really yours because the immune system is what your specialist is doing. So this is really up your alley. Though of course a lot of things else are also up your alley. Now the vaccine trials are on and while we have heard a lot about the modern trials we don't seem to have heard as much about the other trials underway. So can you give us a brief background of the trials and which phase we are at the moment on. Some seem to have also entered the human trials. So this is in a sense let me make a splashy statement. For the first time in human history we are simultaneously making vaccines by the oldest and by the newest possible methodologies all at the same time. So what is the oldest possible methodology? The old smallpox variation followed by Jenner's cowpox vaccination followed by Pasteur's vaccines for a variety of microbial infections. And the simple argument there was take the microbe that is causing the disease weaken it or kill it so that it's safe to be injected but it will still generate an immune response and then inject it get an immune response hope that the immune response is protective hope that the immune response is long lasting and you have a vaccine and either you are famous or you're rich. So that's the old model. Are we doing that for SARS-CoV-2 and COVID-19? Yes we are. There are at least two or three companies and organizations making that kind of a vaccine by just growing the virus killing it or attenuating it and injecting it and Sinovac Chinese company is making that vaccine and is apparently in early phase trials. So that's one end. The second way of making a vaccine is to take components of the virus particularly components against which the immune response is likely to be protected that is the outer coat proteins of the virus. So you can make the outer coat protein in a variety of ways. You can mix it with adjuvant. Everybody will remember having taken tetanus toxoid shots and for those of us who've been brave enough to actually look at the syringe the fluid in the syringe is milky and it's milky because there's a little bit of adjuvant alum mixed with alum suspension in which it is so it's a suspension. So basically you take the viral protein that you've made in a variety of ways put it with an adjuvant like alum inject that and again hope that you get protective long-lasting antibodies and I'm going to keep harping on this protective and long-lasting as we go along. There's a very large group of many many many vaccine makers in very very many countries who are trying basically to take the spike protein of the SARS-CoV-2 virus to put it with adjuvant to formulate it with adjuvant as a vaccine injected and make a vaccine and again at least a couple of those are in early phase. So this we called also as a DNA vaccines. We haven't gotten to the DNA vaccine. We haven't gotten to the DNA or RNA vaccines. No no no. So these are the oldest and the second oldest modality of making vaccines and we are doing both of those for SARS-CoV-2. The third modality of making a vaccine is actually not to put in pre-made viral protein material which is going to serve as the target for the immune response. Instead what you do through the vaccine is to give your own body the genetic information based on which your own body will make the viral proteins in a micro environment where in the body wherever you inject it so that an immune response can be generated. So rather than the first two approaches this category of approaches are approaches where you don't give the viral target to the body as a vaccine. You give the information to the body and let the body make the target and respond to the target and in this category so this is the new 21st century category of vaccine design. There is currently as far as I know no licensed vaccine made by any of these categories. It's that new and in a sense unproven category or at least. I think developed it for Ebola but it really didn't go. Well it's been developed for a very large number but yeah it's been developed for Ebola but it's never been properly deployed in any scale and there are three subcategories to this general category depending on how you give the information to the body of the vaccinee for making the viral protein. So one is you put the information for the SARS-CoV-2 protein making into another virus which is relatively safe and these are adenoviruses or adenolike viruses and you inject that virus. So what is currently in the news currently meaning over the last 72 hours in the news as the so-called Oxford vaccine is the vaccine that is based on a chimpanzee adenovirus into which information for the SARS-CoV-2 coat protein has been put in and therefore when this engineered adenovirus is put into the vaccinee the vaccinee's body will take the information and will make the SARS-CoV-2 protein and will generate an immune response against it. The second category is that also apart from the Oxford virus one of the ones which are being under in clinical trials at the moment is also a Chinese vaccine. In fact none of the examples that I'm using are unique to any one group. So multiple people are growing the virus, multiple people are making the viral protein, multiple people are making all sorts of adenoviruses mostly adenoviruses of different kinds carrying the information and the fourth category is and the CanSino group both of these were actually one of the early enlistments WHO for the clinical trials. That's correct. So the fourth group category is of DNA vaccines where again instead of putting the genetic information for viral protein making into a into another carrier virus you simply take the DNA appropriately configured and you inject the DNA and if you've done your formulation correctly that DNA is used again by the vaccinee's body to make the viral protein and to make generator immune response against it. And the last category which is exemplified by Moderna is since DNA is converted into RNA is copied into RNA and then RNA is copied into a protein rather than giving the viral protein information as DNA Moderna is giving the viral protein information as RNA directly and again letting the body make the viral protein and respond. So those are the categories and in each one of these categories there are a large number of people who are trying to make vaccines the world. So adenovirus RNA or DNA vaccines all these are in that sense new vaccine making have not been tested earlier? Yes as you pointed out there are a couple of examples of adenoviral vector vaccines that have come close to being deployed DNA and RNA vaccines haven't come that close but all three modalities have been under development and investigation for oh easily 25 years. Okay so in the laboratory they are not novel as a matter of fact none of these approaches is particularly novel because many of them are simply repurposed from earlier candidate vaccines that went a certain distance and then didn't go further because there didn't seem to be any demand for them and have simply been repurposed for them. They originally started with SARS as the target. SARS, Mars and Ebola but none of them lasted long enough for them to really get into full-blown clinical trials and then come out to the successful version. Well to be honest they lost capitalist value lost capitalist value and therefore did not go further and I would insist on that rather than saying that they lost societal value I don't think they lost societal value but what they did lose was what I'm in fact calling capitalist value. In fact following what exactly you have said that expecting a coronavirus pandemic after SARS and Mars this should have been funded so we are ready at least well before it hit us. So we got a 10 year more than 10 years time for preparing ourselves which you don't seem to have used. Well okay so let me do a little disagreement. Yes and no and then no my point of disagreement is because I think in fact that the actual technologies that are being deployed were in fact technologies that were developed and publicly funded might with taxpayer money in pretty much every country and the technologies were developed in the laboratory far enough that in fact we were ready technologically which is why all of these in a matter of weeks not even really too many months have come out of the laboratory and have gone into clinical trials. What we what I agree with in your statement and that what we have not prepared for is the downstream. Who will manufacture it? How will we put together sufficient accredited safe manufacturing to scale so that we deliver the vaccine to communities across the world as they need them without forcing them to pay through their noses for it. This component of a human response to a pandemic we have not learned at all and that's where we are going to arrive by the end of this year where the laboratories will have done using publicly funded resources what they are promising to do and then we will begin to fall on our faces because we have not done the economics of technology dissemination. Which is where the virus wars seem to be shaping up with Trump saying warp speed nothing to do with China we do not accept WHO's premise it should be available publicly and so on but we'll come to that a little later. So coming back to the the kind of vaccine development that you talked about and three of them are currently clinical trials and I'm sure more are but at least three have been talked about one is the Moderna vaccine one is the Sinovac vaccine and the other is Oxford vaccine. Coming to the Oxford vaccine because you talked about the last 72 hours news cycle that was also connected to Astro Genka which is a British company and also to Serum Institute in Pune they seem to have a retire. So the failure of the Oxford vaccine trials at least partial failure you think that is no longer now a candidate? No I think that it's a candidate I wouldn't call it a failure so let me clarify since you bring up the detail of the Oxford vaccine essentially the most likely expectation from pretty much all of these vaccine approaches that we talked about is that all of them will work to a certain extent meaning will they generate some degree of protective antibodies and protection? The answer I suspect will be yes and that has in fact been borne out some in the monkey experiments preclinically some in both the monkey experiments and the initial small handfuls of humans who are immunized with them that antibody responses have been generated that are that have protective properties and in the monkey experiments there is actual protection however and that's where the qualification about the Oxford vaccine appears to begin is protection a yes no phenomenon and no it's not so essentially what seems to be happening is that in the Oxford vaccine monkey experiments unless I'm misunderstanding the data there is clinical protection meaning the monkeys don't become diseased there is a virological protection partially in the sense that the lower lung load of virus is substantially lower but the viral load in the upper respiratory tract does not seem to have gone down as dramatically now what this means if it means anything at all either in terms of success or failure is quite unclear but I would think that the likelihood is that as a first generation vaccine this is going to be as as successful as the scientific vaccine or as successful as the as the Moderna vaccine or or indeed any of the other vaccines I don't think that we should be expecting too much of any of these in the what I'm calling series of first generation COVID-19 vaccines that will begin to come out by the end the Moderna and the Sinovac vaccine seems to show that the monkeys did not get infected that when they were infected later by the actual virus yes and no again it's not clear to me that the monkey experiments in the Moderna and the Sinovac vaccines were as extensive as those for the Oxford vaccine and both of those showed substantial reduction in in in virus load and so it's all you know give or take a little bit it's all comparable and they're all within the same ballpark I would think at the moment so you think that the vaccine is still very much in the race absolutely okay so the question is we have three candidates in the race who have gone to a certain distance others may have that we haven't received enough notice about them partly because they may not be as well connected to media or needing the share price boost which some of these companies seem to do so there is obviously both these angles playing here but we would say at the moment probably there are six to eight candidates which are which have started running in terms of what would be called the two class of trials that are there so both these vaccines both this these set of vaccines and a few others are doing clinical trial one and two now what's the difference between the one and two series of clinical trials yeah so um keep in mind that um all the preclinical work that we are hearing about falls into two categories before I get to the clinical trials the preclinical work is immunizing animals uh getting antibodies from them and testing to see whether they have protective properties this is universally true so there's a hundred and something vaccines registered in clinical trial registries across the world for prospective trials and I suspect that at least in two thirds of them if not more and the simple experiment of immunizing small animals with them mice rats rabbits guinea pigs and finding antibodies with protective properties have been successful so that's one the monkey experiments which is where you can actually look for protection because you can infect the monkeys with SARS-CoV-2 and look for quasi real-life protective capacity of the vaccine have been done for much smaller numbers in part because monkeys are expensive not easily available in part because monkey centers which do monkey experiments using SARS-CoV-2 are even rarer so groups are lining up and uh on a waitlist for this so those are this handful that we are talking about in the clinical trials the first stage of clinical trial is to take relatively small numbers of people certainly less than 30 usually about a dozen or so um and the formal question you are asking in a phase one clinical trial is whether the vaccine is safe or not so the primary stated um intention of the clinical trial in its first phase is simply safety not either um it's the ability of the vaccine to generate an immune response leave alone the ability of the vaccine to protect okay however since you are immunizing a few people you will take blood samples and you will test those blood samples to see whether there are antibodies and if there are antibodies what the protective characteristics of the antibodies are if there are any and it is from those very tentative preliminary results that we are hearing noises okay all over so this phase two clinical trial will be with larger numbers of people and will begin to ask questions about does the vaccine reliably generate a protective immune response i have i have as yet not formally heard that any of these trials has begun phase two although i may be behind hand on my information um i do expect that within a matter of weeks people will start phase two clinical trials and in fact as i said some of them may have started already but we have no result suddenly from phase two clinical trials is yet and it is in the phase two clinical trials that the ability of the vaccine for mutations the vaccine candidates let us call them to generate an immune response that looks protective will be tested whether the vaccine in fact protects against actual SARS-CoV-2 infection and COVID-19 disease or not will be in a yet further stage of the clinical trial and there depending on what the incidence of infection in the community is very large numbers of people may have to be recruited for those trials that's a phase three trial that's a phase three trial and it's in those situations it's with respect to those situations that people are now talking about controlled human infection models for rapidly validating the protective capacity the actual protective capacity of vaccination where you will take relatively small numbers of people vaccinate them give them deliberately give them infectious virus with appropriate safeguards and therefore ask whether the vaccine protects or doesn't protect with quick definitive results from relatively small numbers of people but with some amount of risk so that's the something which is new this is not a normal vaccine development program no the the controlled human infection model chimps as they're called has not as yet been used to license any any vaccine currently in the market all vaccines currently in the market that we have followed the conventional phase one phase two phase three trials that we talked so when you talk about the phase three trials that takes the longest time it takes the longest time for a variety of reasons large numbers of people are required for statistical reliability and you have to wait for long enough for natural infection incidents to accumulate large numbers of examples of disease in both vaccinated and placebo so it can be about three months four months six months oh i can imagine that if by then across the world transmission efficiency of COVID-19 has dropped substantially phase three may take longer than that so that's why we are talking about the controlled human infection model human infection model that's the reason yes okay so if this happens say what the United States is saying they'll have a vaccine by fall we still have the question of scaling up production we are not entering into the issue you have raised whether it will be available at a price which people can afford particularly the global community this is of course the battle which has been now just fought in the World Health Assembly as you are aware of and the United States and the UK being particularly unhappy with WHO more or less throwing its weight behind the argument and which India has also passed you to that this should be a global public good which Chinese prime minister president seems to have agreed to so do you think that this issue of scaling up production before we go to the in who controls that scaling up production particularly if it is the old-fashioned vaccine will be simpler um actually surprisingly scaling up production is easier with the what I call the newer category of vaccines the adenoviral vaccine the DNA vaccine the RNA vaccine these are paradoxically far easier to scale up in fact as you go from the newest method modalities of vaccine design to the oldest scale up becomes technically more and more and more difficult in fact that's the major reason why so many companies and organizations and groups across the world are trying to make vaccines in these relatively new unproven I suppose you could say modalities because scale up is going to be much easier if and when one of them or more and more than one existing facilities that countries have for instance a serum institute or the afghan institute they cannot produce live back live or inactivated vaccine oh in the existing scale so so none of the technologies is difficult in the sense of these biotech industrial organizations being unable to absorb the technology it's simply that the so there's a built-in limitation how much virus can you make in one liter of tissue culture is a limited so it's not so much a matter of knowing how to do it it's a matter of how many millions of liters and it's simply the physical infrastructure of scale and that's going to be for example sine of x problem sorry to interrupt something you have to build it a new it has to be built specifically for this purpose exist no it doesn't but keep in mind that if we are talking about a global demand over a very narrow window for vaccines we are going to need more doses of vaccine per month than we have ever imagined okay and it's in that scale will lead that making whole virus inactivated vaccines is going to I suspect run into scale up difficulties and that's where the RNA and the DNA might in fact be a little easier for scale up okay so what you are saying is that in that sense the advantage to scaling lies with the newer vaccine technologies so it's not very surprising efficiencies of the newer technologies tend to be higher than older technologies in a sense yes okay so if this is successful say in the human trials phase three trials and if the controlled human infection strategy works so do you think a target of say fall as the Americans say or September October is realistic right so let me say something about benchmarking and decision making I think it's entirely possible if the pandemic continues to worry the world as much as it is wearing the world currently it's I think it's entirely possible that regulatory authorities across the world will accelerate approval processes so that with evidence of immunogenicity meaning that the vaccine generates an immune and antibody response and that the antibody response in laboratory testing has protective properties that much might be eventually approved as sufficient for licensing I don't know this but it's it's at least possible beyond this there will have to be a formal clinical trial for the infection which would be the the orthodox way to go or the controlled human infection regardless do I think that by autumn fall as the Americans call it we are going to have a vaccine rather than a vaccine candidate I doubt it do I think that we will get there by say next january or so I think that by next january we will begin to see the first clear unambiguous results that multiple different vaccine candidates do detectably well in protecting so my guess is I suspect a little uncharacteristically I'm being a little optimistic but my guess still is that by early next year we will begin to see this data I doubt seriously that we are going to see the unambiguous data which allow regulatory approvals by the coming on okay and the last question if we have it by end of the year beginning of next year then parallely we could scale up production so that when it hits us that means we have this vaccine scaling up should be relatively faster so you mentioned that the serum institute of India which is one of the world's major generic vaccine suppliers has a tie-up with the Oxford vaccine development group and that tie-up in fact is an interesting one aimed precisely at what you're talking about which is preemptive scaling up and the interesting part is the preemptive part by and large you would begin partnerships of this kind you know almost franchising partnerships of this kind for scale up across the world in multiple centers when you have a vaccine that's working okay and in that sense I'm pointing out that what's interesting here is that this is a preemptive scaling up in the sense that the serum institute is investing in a speculative scale up of the Oxford vaccine at least from their from their own description that's what it sounds like yes in fact they have said that we can afford to spend the money because it's our money we don't need any approvals so the Poonawallas have said this is okay for us and as you point out they are one of the largest in the world in terms of generic manufacture AstraZeneca is an interesting case because this is why the UK government has been against the patent pool on the in the vaccines being declared as public good as much as Mr Trump so always have the flip side of public funding in terms of the Oxford vaccine is publicly funded but it then becomes privatized to AstraZeneca and then of course not available to the rest of the world yeah so that's interesting and so keep in mind that AstraZeneca wasn't born as a UK company it was a it was born unless i'm mistaken as a Scandinavian company but with with multinationals the point of origin becomes pointless after a while but but the fact of the matter is that this is not really to do with Moderna or AstraZeneca it is to do with the broader both practical and ideological commitment of how governance and major industry in western political economies are configured to be complementary to each other so the the the US and the UK governments will in fact point out that their public sector contribution of science and technology development is in fact intended for the marketplace to take advantage of so there is there is an element of the generic ideological fervor involved in in their positions as well and of course the fact of the matter is that what they will do is sufficient negotiation that their national populations will have some reasonable access built as in in return for their support of these companies in the international arena for intellectual property right protection so it's going to be a complicated dance of who's trying to get what advantage for which corner of their own and and i suspect that the straightforward position that we are spending public money across the world in trying to deal with a problem that's worldwide and that therefore we should simply all of us get together and spend whatever money is required to make the solutions available across the world that apparently common sensical point is i suspect going to get subjected to a major barrage of special interests it's interesting the salk vaccine if you remember johanna sol is a salk was asked exactly this question and he went to patent it and he said can i patent the sun so it belongs to the people the salks are no longer the ones who are there even now bat batting purified insulin and yes earlier in fact the same thing that he he sold he gave the patent to the university of toronto for one dollar and when he was asked he said it's not my insulin it's it's everybody's insulin yes that actually comes before salk so you know that there are there are different ways of looking at this yes but and that's where we are going to be those are going to be the major wars in boardrooms across the world come next year yeah and i believe satyajit that this will be a repeat of the aids wars and ultimately the fact that once you know that this works repeating it is relatively easier and therefore that compulsory licensing to other mechanisms will also come into play so i don't see that this will take 10 years which is what aids back aids drugs took before it became accessible to the poorer sections i don't think it's going to be that long but that's a hope that's you where it actually with you let me add something to what you said that may be interesting and that is you see the anti hiv anti aids drugs were being developed in relatively small numbers of laboratories primarily distributed in the development here is an extraordinary distinction that i think we in india and in fact we across let me say the global south should not lose sight of and that is we have friends and colleagues in laboratories of the global south who are making sarkov to covet 19 vaccine candidates using exactly the same methodologies and technologies that are being used in these other places there are a bunch of efforts in india for example to make vaccines by one or the other of these methodological categories that we talked about and my argument is that we need to be heavily supportive of these efforts because they underline a major tactical point so this is not about they are necessarily succeeding and making great vaccines that will go out i hope that they do but it's but my support is not dependent on that i'm arguing that we should be supportive of those because it undercuts patent claims as and when they begin to get made okay and that i think is and i'm saying this publicly is a critical issue in underlining the point that the state of art knows how to do this the world over okay and therefore we need to be both supportive of ongoing efforts and we need to demand the poorest of us as countries need to demand hey can you support some of our scientists and technologies to try to make a vaccine candidate good so the battle continues absolutely your vaccines which it did over the issue of aids and as i said hopefully it'll be much shorter and if you strategically invest in some of the issues you are saying some of the areas of research development as you are saying then we'll be in a stronger position thank you satyajit for being with us sharing your knowledge about a rather complicated issue which is of great interest to people as and when such pandemics or other such issues come up this is all the time we have a news click today do keep watching news click and do come back to our also visit our website