 Hello and welcome to NewsClick. Today we have with us Dr. Satyit Rat and we'll be discussing the vaccine trials which now seem to be entering phase 3, which means that they'll be much larger in number and we could in another 3 to 6 months see successful trials and possibly its deployment. Of course this round itself can start with perhaps looking at the more those people who are more in danger, the hospital staff and so on and maybe some of them will also be covered in this phase trials, this phase of trials. Satyit, it could welcome information, we now seem to have at least 4 vaccines which are going into phase 3 trials. Oh absolutely, it's welcome news, it's not surprising news at all, at this stage any surprises would have been unpleasant surprises so I'm glad that there are no surprises in this. All of these have been tested in at least 2 animal models and what they did in those animal models, they seem to be doing in these small scale human trials. So I think that we are on track and all of them have entered phase 3 clinical trials already. Except the model now which is yet to start its clinical trials. Well they're doing the paperwork in the group and clinical trials are starting in what 5 different locations across the world, in the UK, in China, in the US, in Brazil, in South Africa. Also in the United Arab Emirates, they have a center where it is being tested, one of the Chinese vaccines is being tested there. So I think that these are expected good results but they are small steps, they are an initial very small step. What do those these 4 reports that everybody is talking about which have come more or less coincidentally together? What do they tell us? They tell us some definitive evidence and they tell us some indicative information. The definitive evidence is that all 4 of these vaccines are safe or let me be correct all 4 of these vaccine candidates are safe over the short term. And on a small number? Small numbers. It's noteworthy that 2 of them are based on adenoviral vectors and 2 of them are based on RNA formulations. No, I think there's one virus which the Chinese are doing which is actually inactivated virus. The current report that we are looking at is the Chinese adenovirus 5 vector based vaccine. That's correct. The inactivated vaccine report has come early. Yes, but that's also entering. So in that sense there are 5 candidates in play. How is it 5? Just one way. There is one. As to the internal RNA, there is bio-intake Pfizer's RNA. There is the Chinese adenovirus and there is the Chinese inactivated virus. In fact, what I'm trying to say is that we are going to see an accelerating large number of these reports coming out in the coming weeks. Because if you look at, for example, if you look at the WHO status update document on the WHO site about vaccines. The latest is I think dated the 20th of July. So it's not that out of date or anything. And in that tabulation, there's a fair number of vaccine candidates which are in phase 1. Oh, that's very large. So those results are going to start coming up in the next few weeks. So we are going to have, it doesn't matter 3, 4, 5 candidates. We are going to see many more in the coming weeks. And I suspect that in all of them, the first result from the human trials are going to say exactly these two things. Let me interrupt you for a minute over here. While the Chinese 2 viruses and AstraZeneca, they seem to have done a sufficiently large number, 600 to 1000 or so. But the model is a small sample, it's only about 6. Yes, there are significant differences in the numbers. And one could always quibble about it all. Keep in mind that the Oxford chimpanzee adenoviral vaccine report that we have, the actual phase 2 level data are not from all samples. In fact, the paper actually specifies correctly that this is a preliminary analysis being reported because all tests have not been as yet complete. So this is why I'm saying that the current step has two components. The definitive component as we said is that these things seem to be safe when people get injections. Safe over the short term, safe in adults, safe in adults of European, healthy adults of European ancestry in the main except for the Chinese trials. So there are caveats, but this is good that they are safe. The non-definitive indicative component of the evidence is that all of them seem to generate antibody responses in pretty much all vaccine candidate recipients. All of these antibody responses seem to show virus neutralization capacity. All of these vaccine needs, these vaccine recipients also generate T lymphocyte responses. Keep in mind that the antibody level can at least be analyzed for, as I said, virus neutralization capacity. The T cell responses at this point have not been and really properly speaking cannot be examined for their protective contribution. So we have definitive evidence about immunity. Just to make it clearer to all viewers, the antibody response will be also protective. While the T cell at the moment, we cannot say what will be the protective response. How do you sort of elaborate a little on that? So you can measure the antibody response in ways that don't tell you whether that antibody response is likely to be protective or not. But you can also do so-called virus neutralization tests with the antibodies. And if they show the capacity for virus neutralization, then it's a reasonable piece of information that they may be protected. They're likely to be protected. It's not evidence of protection, but it says they're likely to be protected. Exactly similarly, you can test to see whether there are T cell responses and there are. But at this point, nobody's done even indicative tests to ask whether the T cell responses have any antiviral capacity or not. They get awake, but we don't know whether they can attack and destroy the virus. That's what it really means. Or the cells which get infected and therefore take out the virus. To be fair, those are much harder tests to do. The virus neutralization tests for antibodies are hard enough to do. Which is why the results between the four papers are for fine readers, the results are a mess. But broadly, they still say this. So we know now there is antibody response. We know now there is T cell response. We know that the antibodies may be able to neutralize the virus in case of infection. But we do not know whether the T cell response will be able to do so or not. At least definitely. So that's where we are at the moment. And that's why of course we need larger scale trials to test it through the fire. So to say of the actual large scale exposure to infection. And as well to see whether there are any possible side effects which can also be harmful. Absolutely. So there are additional nuances to this. Especially when you consider all four reports. That are still not adding the fifth one, which is also entering clinical trials. Because we don't seem to have a report about it or at least not recently. So the interesting thing is that the adenoviral vaccines as well as the RNA vaccines. On the one hand they are safe. On the other hand, they are pretty damn painful. They are pretty damn painful. If you look at the data, the amount of redness, swelling, local tenderness, a little bit of fever. All of this is quite notable. So for people of sufficiently advanced age such as you and me. It is reminiscent of the vaccines that we used to take when we were children. Where the arm would swell and you would feel horrible and miserable for a day or two and so on and so forth. Now, is this a huge problem for these vaccines? On the one hand, no. In the sense that these are transient effects, they'll pass and if the vaccines work, it's well worth it. But in this day and age of social media, mediated amplification of anti-science, irrational, anti-vaxxer movements. This is something to be considered about how successful implementation and acceptability of these vaccines will be. Well, that hopefully will be more in the United States. For some strange reason, there is a strong body of people who do not believe in science, believe in either in flatters. By the way, their numbers are also growing and of course the anti-vaxxer. But coming to the question of ill effects, possible ill effects. The Moderna report seems to indicate that a few more, shall we say, beyond paid effects have also been observed. Is that correct? You know, they've reported one severe effect I think. Frankly, I'm not inclined at this point to be judgmental about it. So it could be, if we have a much larger sample, we find that this is an outcome. I think that the data and safety management boards have all correctly generally supported movement forward into phase 3. And in the phase 3, we will see what the results look like. Keep in mind that the numbers in terms of the magnitude of immune responses of the Moderna vaccine seem to be larger than that, for example, of the Oxford vaccine. Now that brings up the second of my particular bees in the bonnet about nuances. Because I think that our listeners should be cautious about the interpretations of these numbers. These are not absolute numbers of universal meaningfulness. So in a sense, different tests with different levels of sensitivity would give different numbers. And since these are very different centers doing their own tests, depending on the local configuration of the test, the numbers would look quite different. In fact, if you look at the Oxford vaccine reporting paper, they've done three different virus neutralization tests. And the numbers in the three virus neutralization tests are completely different from each other. So I think that it's important to keep in mind that these absolute numbers may not mean anything other than technical differences. Yes, I guess also the ultimate test will be do they protect us or denote? Absolutely. And the numbers are only very rough indicators and they don't really tell us where it will protect and where it will not. Plus what you're saying, the calibration of the numbers itself is a problematic issue because they're not calibrated to a common quote unquote viral utilization standard. So these are the caveats we have to take into account, but the bigger caveat is how long the if there is protection, how long the protection will last. Absolutely. That's other big issue in this game that if some of the reports are true, it is possible that we might need to have vaccines every six months, every year, every two years if we are lucky. Absolutely. The Oxford trial, for example, shows data until day 56 or so. Some of the others show even less. So all we know is that within a month of vaccination, pretty much everybody makes a respectable antibody response with some neutralization capacity and pretty much everybody makes diesel responses, both of which are good things. But that's all we know at this point. There is yet another nuance since you bring this up that our listeners might find interesting and that is the use of boosters of second doses. So the Oxford vaccine, for example, uses a minute number of people, 10, to give a second dose of the same vaccine and it shows that the second dose improves the antibody levels, although it does not show any measurable improvement of the T cell responses. Again, these are all small, useful, minor findings. Nothing can be said from any of this of definitive public health significance at this point. And all a small technical value. But the good thing is adverse reactions have not been observed, except one may be outlined in the modern case, but all other vaccine trials phase one, phase two, the primary purpose of which is also safety. So that has been at least found to be. Yeah, we should keep in mind that this conflation, this merging of phase one and phase two carries its own difficulties. Phase one is formally supposed to be about safety evaluation. Phase two is formally for vaccines supposed to be about definitive evidence of whether good reliable immune responses are generated. And to have published reports that say that the immune response related reporting is preliminary, partial and incomplete because this is a sort of phase one oblique phase two trial. It leaves us slightly uncertain about just how robust the evidence is for the generation of immune responses. When I look at the numbers, they look good. I will not at all please any worries about it. Nonetheless, we must remember that phase one and phase two have these two clearly distinct. Purposes in formal terms and while the first purpose has been served well, the second still seems to be somewhat shall we say soft evidence, good evidence but soft evidence. So hopefully with more tests, et cetera, we'll get a better picture, but this another report comes which they seem to have promised we might get a better picture. And if we start the clinical trials early enough for phase three, some of that evidence will also help us make a better judgment about these things. So all in all, cautious optimism to caveats. We do not know how strong the protective action is. That's the one question mark. We have to see how it really pairs on that. And the second is how long will the immune response last and when we might need the booster or an additional vaccine or the vaccination again. But leaving these two things out. The last question. It's also interesting that we have two Chinese vaccines, Pfizer, Moderna and Oxford. All three seem to have been backed by the US. What is the warp speed project? Lightning or whatever. All in the warp speed. I see. Yeah. No, I'm raising the issue that will it also mean that they will have control over the vaccine itself by having given such large amounts of money. Clearly there is control because clearly governments have already made deals with the vaccine developing organizations about priority in vaccine supply in speculative terms. The US and the UK government seem to have made some sort of deals about priority supply to them and so on and so forth. All of which comes back down to something that we've been discussing on this forum over the past two months. And that is that the vaccine technologies in the plural themselves are not going to be the bottleneck. As we can see, we are already at four or five in the coming few weeks, not even months. In the coming few weeks, we'll have even more candidates coming to exactly this stage. There'll be large numbers going into phase three. By the end of this calendar year, as we said earlier with cautious optimism, we will in our likelihood begin to get first generation. Protective efficacy, at least for short periods of time and significant production in disease susceptibility. The real problem is going to be what on the one hand is the plan for manufacturing supply chain delivery and implementation of vaccination. And even more, what is the legal, political, economic struggle to ensure rapid affordable actual delivery of the vaccine to the world sport. And if we want to do that, that is the government has to start creating the necessary infrastructure and the legal, as you called it, the legal, political, economic strategy for doing so. Because if you don't, then we'll get what is happening with remdesivir. The medicine is either available at black market rates because it's simply not enough supplies. And it's still, even when the supplies are available, it's 30,000 rupees to 35,000 rupees for a treatment. Six injections over five days, you get to spend 35, 36,000 rupees, which probably costs all of 1000 rupees at best. So you are seen profiteering on COVID-19 on a scale. And since we have not seen any action by the government on remdesivir. The question that arises that are they going to wait for the Indian vaccine for the Indian people? Or are we going to see what you said? What I understood you to say that if the vaccines succeed, duplicating it with local skills and local infrastructure is not a problem. It's not a problem provided governments address the issues that we've been discussing and on proactively. Whether the government will do so or not remains an open question. But if this is the time to talk about it and not after the vaccine is available to the rest of the world, then we start thinking about how to do it. I mean, if we look at our response to the COVID-19 pandemic, this has been almost of the same kind. That we first issued the lockdown orders and then we decided what do we have to do under the lockdown. There's no preparation, there's no blueprint for the lockdown, except one announcement by the Prime Minister. Four hours lock everything down and then it became a police action. Curfew across the country. That was the effect of the lockdown. So if we don't prepare now and we have six months to be trying to do so, we may be able to say both. Yes, absolutely. And this is particularly important when the international fora in which to do this kind of global health policy coordination on the one hand, global trade policy coordination on the other hand are in uncertainties. The US has pulled off the WHO, the World Trade Organization lacks a head currently. It also doesn't have a lung or a stomach because basically the dispute settlement body, which is the key power of the WHO, that has one member and they can't meet other three members. The US has not allowed any member to... So under those circumstances, governments have to come up with innovative proactive strategies for planning for this. And at least in the public discourse, there doesn't seem to be any evidence that it is doing so. And again, from our viewers that under Indian law, which is basically the patent act, we have complete powers to do any of the things we have talked about, compulsory licensing, under health emergency. All of these measures are available in public interest, both of which are in this case two are available. So the question is having, as you said, the political will to do so because economically, there is really no bar. If you can, what is it, give lakhs of dollars of rupees as largesse in some sense to the capitalist class. Surely for public health, this kind of money is also available. And other issue that you talked about technology infrastructure, actually we have a huge vaccine infrastructure that exists in the country. So using that for Indian people should not be a problem. Oh yes, absolutely. It is the political will that is the primary part of it. And the political will to confront the countries which at the moment are the ones personally say, and sabotaging the global organizations that exist, which in this particular point are really particularly important. The question is not how good they are. The question is they exist. And the absence of those organizations mean the lack of coordination for public health at the global level. And this is not a disease that you can live with and say, okay, doesn't matter. Let's hope things will improve. You have to stop it at the moment with vaccines. There doesn't seem to be anything else that will work in the long run, except the vaccine as of now. Absolutely. Okay Satyajit, thanks for being with us, explaining the intricacies of vaccine development and immune responses. I'm sure that we will continue to throw light on these difficult issues which have to go beyond the headlines of the newspaper. This is all the time we have a news click today. Do keep watching news click and do visit our website.