 Hello and welcome to NewsClick. Today we have with us Dr. Satyajit Rat from National Institute of Immunology. Satyajit, I think that has been sort of going around recently is a malaria vaccine. We have had times of India extoll about it in great detail. We have had even New York Times has commented on it as a major development. This vaccine which has had some field trials now, some results are available, talks about 47 percent cover if you will of for small children regarding malaria infections also claimed to be the first vaccine against parasites. Now what do you think this represents? So this is the vaccine from GlaxoSmithKline that was initially made in the US Army laboratories and since then has been developed by GSK in association with the path malaria vaccine initiative which is a multilateral public interest consortium. There is as is evident a very substantial financial and otherwise interest of the Bill and Melinda Gates Foundation. It is an interesting vaccine because it is a truly genetically modified protein. So it takes the surface coat protein or a fragment of the surface of one of the surface coat proteins of falciparum malaria and it is from the life stage of the malaria parasite that mosquitoes inject into the body. It then stitches this fragment of protein to a protein from the hepatitis B virus against which we have a very good vaccine. The nice thing about the hepatitis B virus protein is that it forms ordered particles by itself. You make the protein, you put it in appropriate physiological solution and it clusters. So it creates particles. So this fusion protein also creates particles and particles are much better to generate an immune response, to trigger an immune response than dissolved proteins are. So in this sense, it is a nice little vaccine candidate that has been around for a long time. It is very slowly gone through a number of clinical trials. It is phase 2 clinical trials in Africa. Remember, this is falciparum malaria. So inevitably trials have been almost entirely as far as I can recollect in Africa in a whole range of countries and all the phase 2 trials which are small trials have succeeded. Incidentally, they started with human volunteers who agreed to be vaccinated and then deliberately infected with malaria to see whether they could be successfully infected or not and that is where efficacy was shown to some extent and therefore that is how it was started. Now the nice thing about this trial is that this is a phase 3 trial. It is a large scale trial. Many thousands of children, 16,000 I believe are to be recruited. The trial has two components. One is very small babies, 6-week, 10-week, 12-week old babies. Remember our immunization program for children in public health, we usually do the bulk of our vaccinations in that age. So if at the public health level you have to introduce yet another vaccine, that would be the age to introduce it at logistically, expenditure wise and so on and so forth. But they have also got a greater than one year age between one to two years age. I forget the exact month slot group of children in whom also vaccination has been done and results are to be generated. Now the trial is to go until 2014. So they have done a mid-trial analysis and they have determined that the second group of children, the one year plus group of children shows a significant protection with the vaccine against attacks of malaria. Doesn't change deaths due to malaria. It does improve the severe attacks of malaria, the very severely ill children that frequency has gone down as well. But if they pool both groups, the effectiveness of the vaccine comes down. So what that suggests possibly is that the very young babies being immunized may not be as well protected, number one. Number two, the bulk of the protection is being seen within the first year. The trial is only just bigger. Now other people have done this, they haven't, the authors haven't done this. Other people have done this, that if you split their data into protection early after vaccination and protection towards the end of the first year after vaccination, protection towards the end of the first year after vaccination tends to be a little lower. Now one doesn't know if this is the case or not. In all of this, therefore, there isn't really a vaccine as far as anybody can tell right now. There may be, there may not be. What there is is some glimmering of an indication that there may be a vaccine. This is better than any other anti-malarial or anti-parasite vaccine that we have seen. And to that extent, the enthusiasm is, I suspect, warranted to some extent. But it is curious that rather than waiting until 2014, which after all is not that far away, they have chosen to do a midterm analysis and to release both a publication and maybe even more importantly an announcement by Mr. Bill Gates in the Bill and Melinda Gates Foundation meeting that here is a vaccine. They're also talking about introducing this by 2015. Now if the trials are going to end by 2014, is that possible as a date to introduce the vaccine itself one year within that? So WHO has said again unusually that if the present data hold up in the next set of analyses, say once you begin to do interim analysis, you can do a whole range of interim analyses. So if they hold up in the next set of analyses, which will be towards the end of next year, and if they hold up at the end of the trial, which is 2014, then because it has gone through a protracted set of clinical trials over recent years, WHO will feel comfortable with these provisos in saying in 2015 that it should be introduced. This is coupled to the fact that GSK has said that it will cost this vaccine, that it will price this vaccine at production cost plus a token amount of additional cost, which GSK has said, I have not seen the original commitments, but GSK appears to have said that it will undertake to invest in a next generation vaccine because everybody admits and agrees that even if this vaccine works, we are going to want a better vaccine. Manufacturing cost plus recovery of the R and D cost which Glaxo Smith and Klein has said is about 300 million dollars, I don't know. So whether the manufacturing cost is just manufacturing cost plus a percentage of other cost. And as you know, the major cost as far as drug companies are concerned have always been about the R and D cost, not about the cost of manufacturing. So that itself makes it, you know, okay, we will take this on phase value, but it's not as clear that it will be affordable in that sense. Oh, not at all. As a matter of fact, I haven't seen any realistic estimates of what it would cost to put it into actual regular immunization schedules for children in middle and low income countries. Also, we have this notion that vaccines are going to solve our problem. Clearly, that's not the case. So our proposal of which there is a statistic that we would be doing well to keep in mind. Remember, this is a trial in extremely poor African countries. In fact, one of the remarkable things about the trial, one of the nice things about the trial is that scientists from African countries were involved fairly intimately in the doing of the trial, which is always a nice thing. But this is in very poor countries. Yet, simply by virtue of being recruited into the trial, deaths from malaria have been extremely few in this group of children to the extent that you cannot even get statistically significant differences simply because there have been so few deaths. Why have there been so few deaths? Because given that they are part of the trial, the children have gotten proper medical care and attention. So effectively, what we run into the danger of saying is that because we either cannot or do not choose to provide the medical care that ought to be the right of everybody, we will substitute it with a vaccine. There are difficulties with this. I think that's a very telling point also because a lot of the single issue programs that have come into Africa distort the public health scenario, but that's really a discussion for another day perhaps. But I would like to come back to you on the issue of vaccine itself. Most vaccines we know are really almost 100% effective and that's what we know the vaccines to be. So what does a 30-40% vaccine protection really mean? At the individual level, that's perfectly true. Should will individuals take a vaccine, that's only 30 or 40% effective. Now many of the people of young India may not even remember it, but you and I certainly remember the so-called TABC vaccine for typhoid, paratyphoid, cholera, etc. that we used to get that showed between 30-40% efficacy over the first year and that was discontinued or at least has fallen outside widespread usage. W also had a TB vaccine, if I remember correctly, the BCG vaccine? We still have a BCG vaccine. We still continue to use it because in very small children, for certain illnesses, it is clearly effective. But yes, it's not certainly universally effective. The issue here is whether the individual is protected or not is one question. Whether for an infectious disease you can break the transmission cycle in the community enough to bring down exposure frequency and therefore bring down the total numbers of cases happening every year or not, these become two separate questions. For large public health infectious disease problems, public health authorities, agencies, tend to think in terms of at least breaking the transmission cycle, if not achieving individual protection. Individual protection is the ultimate ideal goal. More than 90% protective efficacy would be wonderful, but most public health agencies tend to think that if you can manage to achieve the break in transmission cycle, you've contributed. I'm inclined to think that that would be a nice thing. Satyajit, again studies have been conducted on what kind of interventions are required for breaking the transmission cycle and it comes down to that you really target the families where there are infections. If you have the public health system to do so, that's much more likely to break the transmission cycle than intervention at the generic level of society as a whole. So, I would agree that it's certainly a proven method for intervening effectively. All sudden, unmedicated bed nets work very well when the program works. I would argue that it's at least plausible in an academic sense to think about a vaccine that breaks the transmission cycle. So, WHO, for example, has said that if we can have a vaccine with 50% efficacy maintained over one year post vaccination, it will be a significant addition in the portfolio of choices for intervention. Nobody is pretending that the vaccine is going to replace anything else. But I think that there is still an issue about single disease-focused approaches in not quite in contrast to, but effectively in competition to far more integrated approaches to public health. And every vaccine hype, deserved or otherwise, tends to worry me from that point of view. Getting out of this malaria issue, there's a larger issue that is there regarding drugs itself. That for instance, after the Artemisinine's introduction, we really haven't had a malaria drug. The last malaria drug for tuberculosis is about, I think, 40 years, 45 years back. Now, do you think that this is a, that we have really reached some kind of scientific limit? Or is it really that there is not enough money in research? There's not enough attention for actually having drugs against what are called the forgotten diseases, forgotten, I don't know by whom, but certainly they are the most prevalent diseases which kill in the world today. I think it's a little bit of both. This is completely prejudice mine in this case, but I think it's a little bit of both. In the first place, I think that there is, it's getting, in science terms, it's getting harder to find targets. Simply because the most obvious and the easiest targets that distinguish microbial infectious agents from us, which are the targets that we would like to make drugs against, many of those already have drugs against them. So it's that much harder to find new ones. It's also easier to find drugs against bacteria, for example, than against parasites because parasites are eukaryotes like us. Bacteria are a whole different category of life forms altogether. So the distinctions are more stark and therefore drugs are easier to find. That said, I don't think it's impossible to find targets. I do think that it is necessary to commit to far more widespread, far more shall we say non-linear efforts to find targets. And our present modality for finding targets, which is really pharmaceutical industry driven, much more product patent driven, tends to try to minimize risk and therefore tends to try to stay within empirically accepted parameters based on prior experience with drugs for the purpose of finding new drugs. That essentially locks you into a relatively small subset of the potential operating terrain for drug finding. And unless we shift away from that into a public sector, public interest, public good effort, that's much more broad ranging. My guess is that we are always going to have this difficulty of self-restricted drug discovery space. Thank you very much, Sir Tijit, for sharing with us your views and your knowledge about these areas and these issues. We'll follow them with you as we go along. I think that we have a long way to go on this as yet. We certainly do. Thank you.