 When I was looking at this topic, what occurred to me was that a lot of the concerns were ones that we'd actually raised in previous presentations. And so going back over the older presentations, what I thought I would do is to give a combination of old slides as well as new ones just in terms of reminders, because what we're faced with, as you said earlier, we did predict some of these issues. So there've been a huge range of reactions if you've been following the news with respect to access to the vaccines as well as to the gaps in vaccine supply. But I actually wanted to start on a positive note, and that is that we do have vaccines. I mean, if we think about the fact that we have three vaccines that have been made and are being used in less than one year, I mean, that's a phenomenal achievement. And I think we shouldn't lose sight of that. And I think we do need to celebrate that particular point. So these are the BioNTech Pfizer vaccine, the Moderna vaccine, and the AstraZeneca vaccine. And as I pointed out earlier, there are a large number of other vaccines that are still being tested and are in the clinical phase of testing. However, vaccine studies do remain difficult. And the next slide, it was a bit of a disappointment that Merck has actually abandoned two of its vaccines. I won't go into the details of this, but the reason they were abandoned was because they did not give us good responses in their clinical studies as the three that are currently being used. So vaccine development does still seem to be, is rather a difficult process. And so let's keep that in mind as well. So next slide, in addition to making the vaccines, we touched a little bit about the bottlenecks on manufacturing. And I went into this in a little bit of detail. And unfortunately, what was predicted at that time does seem to be the case. Making these vaccines and scaling them up is not as trivial as one would anticipate. And so a lot of the issues that are going on at the moment are with respect to the companies either not being able to meet the demands or meeting them in the appropriate timeframe that they were expected. And the EU in particular has been posturing quite a lot about this in the last week. Now anticipating the bottleneck, the next slide, we talked about how to go about getting global and equitable access, accepted the fact that there was not going to be enough for everybody. And this gave rise to these initiatives that were looking at advanced market commitment and also how to get vaccines supplied, particularly to low and middle income countries. And WHO came up with a mechanism for thinking about how to prioritize groups to vaccinate, which not surprisingly starts off with the frontline workers and then getting into the more adult population, those at risk and before getting up to the rest of the population. So next slide, please. Unfortunately, as we saw, this gave rise to vaccine nationalism. People beginning to kind of queue jump if you want to call it for that, call it that where lots of efforts were going on in terms of making bilateral deals with the production, with the companies. But keep in mind that GAVI, which again was recognizing the fact that they needed to be, so this is the global vaccine initiative, recognizing that there needs to be vaccines available for low to middle income countries, came up with a list of 92 countries that would benefit from these global initiatives. And this next slide, this gave rise to what Jimmy has sometimes referred to, which is the COVAX facility. So the COVAX facilities is led by GAVI, WHO and SAPI. And as just said, the idea here was to try to guarantee a fair and equitable access for countries. So this was trying to secure 1.8 million doses for the 92 countries. And underneath that, it shows you what COVAX offers. Now, the problem or looking at equity, basically, they're trying to aim for covering at least 20% of the country's population. So not the entire population, but getting the vaccinations up and running, offering the number of different types of vaccines. And the problem is that the next column there is the caveat. Vaccines to be delivered as soon as they're available. And the idea was to actually treat the acute phase of the pandemic, and then which would then help rebuild economies. I hadn't actually seen any estimates of the global loss, but COVAX estimates that a vaccine would prevent the loss of about $375 billion per month to the global economy. And that's a staggering sum that I hadn't actually appreciated. So next slide, let's look at what the AU has been doing. So that's the African Union. And this is information derived from this month. So the AU has actually made orders for 270 million doses. This is from Pfizer and AstraZeneca. They actually list Johnson and Johnson there as well. But as far as I'm aware, Johnson and Johnson don't have a product on the market yet. And the funding for this has come from various African sources here with an advance commitment of $2 billion. And so under COVAX, they will provide 600 million doses in Africa. And yes, the anticipation here was that first doses would become available in March. And if you've been following the news in Kenya, the next slide, please, in Kenya, there have been recent orders that have been made for 24 million doses. This will cost the government $43 million. And this calculates at a cost of just over $7 a dose. Now, this is twice the amount that was originally anticipated, if you remember, back to my earlier presentations. And the Kenyan government has basically come up with an idea about how these would be used, obviously starting with the frontline workers and then going into those who are more susceptible. Now, the problem in all of this, of course, is that we don't know whether the companies are going to be able to meet these dates in terms of production and delivery of these vaccines. So next slide, please. So continuing along the access to vaccines, so vaccines nationalism is giving way to vaccine diplomacy. And this just shows you an immature of Africa. Unfortunately, I've concentrated on Africa, and I hope the Asian colleagues will forgive this. Those countries that are listed in red will benefit from the COVAX mechanism. But those that are not listed there, so countries like Morocco, Egypt, Algeria, South Africa, they've been made there. They're out of this. And so they've been making direct contacts and linkages with the vaccine manufacturers to get vaccines directly. And in fact, some of these countries have already started receiving vaccines and they are being used. Now, it's one thing to actually get the vaccines. The next slide is what we're also seeing is that actually distributing the vaccines is not as easy as speaking up next earlier, please. Go back, please. Yeah. So the speed of vaccination. And this is information showing how fast countries have been able to move in terms of getting their population vaccinated if they've had vaccines available. And you can see that some of these smaller countries have been doing much better than the larger countries. And so having vaccine is one thing. Being able to distribute it and get it out into your population is actually also proving to be a challenge. And so I hope that countries that don't have vaccines available yet are taking these types of things into account and getting themselves ready for vaccinations once they become available. So next slide. So this was the big question that Jimmy was asking was, when will global herd immunity be achieved? There's a little bit of discrepancy in terms of what percentage of the population needs to be vaccinated. I've seen figures ranging from 40% up. I think 70% seems to be the safer bet. And next slide, please. So if we look at the countries where you're already beginning to have a large enough percentage of the population vaccinated, people are beginning to look at these countries in particular interest. And so for example, in the Israeli situation, they have vaccinated just under 130,000 people. And following up on those particular people, they only notice 20 cases of COVID. And this 20 cases were mild symptoms. None of these were severe symptoms. So there's going to be a lot of interest in following up on people as they get vaccinated. And we're going to learn a lot more about the vaccines that are being used, how much herd immunity this will impart, and what percentage we need to get to before we start to become a little bit less concerned, less concerned, I'm not saying not concerned, less concerned about the effect of the vaccine, about the disease itself. So next, please. So we're still in the early days of both pharmacovigilance as well as efficacy assessment. Because don't forget that the efficacy assessments come out mainly from phase three clinical trials. And we need to get efficacy data coming out now from the much larger population that's being vaccinated. So questions that we had posed earlier in earlier presentations, how long will the immunity last? Will vaccination prevent virus transmission? Is one vaccine better than the others? All of this type of information hopefully will start to come out soon. And actually, are the vaccines still safe? And safe in the different demographic groupings? And what is the vaccine efficacy versus effectiveness? And there's a little bit of a difference between the two terms. Efficacy is derived from clinical data, whereas effectiveness data is derived from when you go out into the general public and start vaccinating. And unfortunately, there is inevitably a drop in vaccine efficacy that is seen when you start to look at effectiveness. Because this is basically done under non-control situations, whereas clinical trials are very controlled. OK, so the question of vaccine efficacy and effectiveness kind of leads me to the second part of the presentation, which is the effect of the SARS-CoV-2 variants that we've been seeing and the implications of their spread and whether they're going to be breaking through the current vaccines. So before I go into the data, I think it's useful just to look at a bit of the nomenclature here, because this can be a bit confusing. And mutations in the SARS-CoV-2 genome refer to actual changes that take place in the genome sequence itself. And viruses whose genetic sequences differ are called variants. And that's the term that we've been hearing more in the public domain. Now, variants can contain a few mutations. And those that contain few mutations belong to the same lineage. And variants can either have the same characteristics or they can have different characteristics. And those which have different characteristics are actually called strains. And so from a vaccine perspective, what we're really more interested in identifying are those variants which have different characteristics, which then might allow them to escape the current vaccines that are being used. And next thing is that the lineages are important to follow because this allows epidemiological study to take place to define how viruses spread through communities. And these are normally revealed rather through next generation sequencing efforts. So next slide. So we have a number of variants that are floating around. And they're not unexpected. Viruses do change. Viruses do mutate. However, some of them are of concern. And so the notable mutations that the scientific community have been concerned with are those that alter the function of the spike protein. And you remember now this is the spike protein that's being used in the vaccine. And it's also the protein that's responsible for initiating infection. And there are three mutations that I've listed there. D6142G, E4840K, and N5012Y. And what that reflects is just the position of where that mutation occurs in the molecule and the change of the amino acid sequence that's taken place from the vaccine strain. So for example, N501Y is an asparagine amino acid residue has been changed to a tyrosine one. So if we look at the variants that have been reported in the UK, there's this one called B117. In South Africa, there's a variant called B1351. There's a new one in Brazil, B1. And there's actually also one in Kenya that's been identified called the titer variant, which is D80A. Now, if we look at these mutations, these mutations actually map in a part of the spike protein, which interacts with, which is important for infection. Let's put it that way. And so that's why the D614G, E484, and N501 mutants are of particular concern. Because next slide. In vitro, they've been shown to be less efficacious or rather overcome the ability for antibodies in particular to be able to neutralize those viruses. Notwithstanding that, however, I think it's still too soon to say that the current vaccines that we have will not work. And there's been an interesting study just published last week from a group in Seattle that's looked at the effect of the mutations and the implication of them, not so much for vaccines per se, but they have a more profound effect on the use of monoclonal antibody therapeutics. And you remember that was the last topic that I covered. And monoclonal antibody therapeutics basically replacing vaccines as a way of passively getting passive protection. Now, because monoclonals are designed for a very specific part of the molecule, unfortunately, what the study has shown is that the Regeneron cocktail of monoclonal antibodies may be quite susceptible to the mutants that are floating around. So it's too soon to say whether the vaccine will fail. I don't think they're going to fail, but they may not work at the same efficacy. Next. And the reason for that is because the in vitro situation is really very different from the in vivo situation. Can I have the next slide, please? Hello, Jimmy, can you still hear me? OK, I'm not seeing the next slide. Is that stuck? No, it is up on the screen. OK, I don't see it on my screen, so I'm going to have to. Slide 25. OK, there it goes. Yeah, all right, sorry. So what I was saying is that the in vitro assays that are being used are extremely, they're very different from the in vivo situation. Because in the in vivo situation following the vaccines, if you remember what I said is that you get a large number of antibody responses, you also get a T cell response. And so it's too soon to say that the current vaccines will not work. And in fact, I was alluding to this earlier that the data that I'm showing you here is actually out of date as of this morning. Because if you saw the BBC News this morning, there is a vaccine coming out from the Novavax company, which is based on a protein vaccine. And the data coming out from there is showing that the vaccine works against both the UK variant and it works against the South African variant as well. Now, in the absence of those vaccines, they haven't come online yet, but that's really good information. Because what it means is that we have next generation vaccines that are coming out from the current work that's going on. But don't forget that part of why the three vaccines that we have currently in work as they were rapid response technologies. And so these companies have actually already started working on the variants and looking at how to put the variants into the next generation vaccines as well. So I think in the longer term, we're going to have vaccines available that will cover all the variants that will come out. The current vaccines will work against the others, whether they will work as well or not remains to be seen. So really, that's what I wanted to cover, Jimmy. I hope that gives you an indication of where we are and everybody else. And so as I finished off last time as well in the next slide is unfortunately for the coming period, we still don't have any choice but to keep security on the top of our minds. Just one more thing, Jimmy, relating to the time frames that you were talking about. I saw a recent publication from the Economist where the intelligence unit of the Economist was actually trying to assess the global access to the vaccines, the current vaccines that is. And what they were saying was that the advanced communities or the bulk of the population in the advanced communities will probably be vaccinated by mid-22. The timeline would extend to early-23 for the middle income economies and stretch out to 2024 for the poor economies. That's assuming that there weren't going to be any other delays in the supply chain. So the supply chain still seems to be the major issue. I think the science side of things can be controlled. Thanks. Thank you, Vish. That was really helpful to analyze, learn what our variants was when we talked about mutations and variants and strain, what those all mean. What is the current state of the vaccine value chain, if you like, global supply versus global demand and so on? I have one question before you go, Vish. I mean, I think your bottom line, including the last report on the Economist you mentioned, is that developing countries, low and middle income countries are a long way from getting this vaccine given current production capabilities and so on. But what if, Vish, we do have a variant, well, not the variant so much. But suppose we find out that the protection of the vaccine is only a year. Wouldn't the developing countries, the developed countries, who are trying to get herd immunity, if it's only a year of protection, they will start all over revaccinating. So buy up all the supply again. Is that what are your thoughts, maybe you and Dieter, about the issue of protection? Is this long-term protection? So indeed, once the developed countries finish vaccinating, the rest of us will get. Or are they going to want it soon again, because it's only a limited period of time. And so developing countries may never get it. That's a great question, Jimmy. I mean, I don't know how that's going to play out. But my thinking is that if we look at what happens with the flu vaccine, where there is a new flu vaccine that's made on an annual basis, and there is a mechanism in place that's been put into place by WHO, where they assess the flu variants that are floating around the globe and try to predict which are the variants that are likely to be present in five to seven months' time. And so the flu vaccines are actually made way in advance of the next flu season, five to seven months in advance. Sometimes they get it right, sometimes they get it wrong. And unfortunately, that's the way if coronavirus indeed goes along that line, which is still questionable. Because at the moment, at least, it certainly doesn't evolve at the same rate as the flu virus does. But I think you could envisage mechanisms coming in place where it would be possible to be able to control future variants provided you can get the manufacturing side and supply side of it in tandem with the ability to be able to come out with the new variants. Do we know about, I read a lot, but countries talking about vaccine production as a security need, are there many plants being built around the world, do you know? Yes. Are people investing in supply? Absolutely, absolutely. So there are lots of new ones going up in place. Lots of people are retooling. The Serum Institute of India has done a phenomenal job. They're actually going to be involved in the Novavax vaccine that I just talked about, this new one that's coming online. They're already behind AstraZeneca. They're behind the other two vaccines that are being made in India. And lots of other countries, again, doing the same. They're actually building new facilities and they're adapting old ones to be able to redesign and re-get into making the new vaccines. Now, what really gives me extra hope is that the Novavax vaccine is based on true and tested technologies that the vaccine companies are more familiar with making. And actually, I think that there are even better technologies that are in line, which will come about in the next six to eight months, which will be even easier to manufacture, I think, than the Novavax vaccine. So I think over this current year, we'll see a huge change in what will be available and what could be designed for future outbreaks as well. You know, just two comments, what we said before. You know, the Johnson and Johnson vaccine, they have very good data. So it's a vector vaccine. And most likely, we'll be getting emergency market authorization in May in Europe. And this is more one of the classical vaccines. And I think that's an important step forward. The other thing, you know, new production side, everybody is working on that. You know, Sanofi is the largest vaccine company, except the one in India. And they didn't develop their own COVID vaccine. But they have, from a former time, a bearing manufacturing cycle close to Frankfurt in Germany. And they're starting in May, producing their Biontech vaccine. And they say they will produce 250 million doses until the end of the year. So there is a lot of improvement coming up. But otherwise, you know, in Europe, for example, with the exception of countries like UK and Israel, where they roll out the vaccination, it's very, very slow because, you know, the order and the promises of vaccine doses getting is not there. Interesting is also, you know, that in Europe, at least, you know, many people are still skeptic with getting a vaccine shot. Germany is good. 67% of the German population wants to be vaccinated. The worst country is France. In Europe, only 35% of people are ready to get a vaccination. So that's an important information to when we talk about herd immunity. If the people don't come for vaccination, you are far away from herd immunity. The other thing is, Jimmy sent me yesterday an article from the CBC in Canada. And there was a nurse. She had both shots, the BioNTech shot. And after both shots, she got positive two weeks after the second shot. She became positive for coronavirus again. And the question is, you know, how can this happen? But we know that immunos people could still carry and transmit COVID-19. So this is something which is important to know again and a clear statement that we will have our non-pharmaceutical interventions, like mask hand washing, will be important for the future. In addition, it could be, you know, the BioNTech vaccine say they have a 95% vaccine efficacy. So maybe this nurse is one of the 5%, which is there or maybe, but we hope not. This is a strain, a new variant, which is not covered by the vaccine. But the good news is yesterday, the EMA, the European Medicine Agency, agreed that the data shown by BioNTech, at least for the UK variant, that the UK variant is fully covered. So let me talk about the boring thing about masks. And there's two occasions which really started the discussion again. And the one is more a global discussion. Everybody followed the inauguration of Joe Biden. And, you know, there was this young poet Amanda Gorman, which fascinated everybody, but also fascinated people because she was wearing two masks. And the other thing is, you know, in Europe, particularly Germany, Austria, they started to say only FFP2 masks are allowed. And you see here our German Minister of Health. And I will tell you why this is important. Next slide, please. So most people use the closed mask. And, you know, there is now a tendency to go away from closed masks. But still they have the importance, particularly in countries where you can't buy FFP2 masks as many as you want. And, you know, the CDC, the US Center for Disease Control, made a study again. And the conclusion from November last year is that experimental and epidemiological data show clearly that community masks can reduce the spread of SARS-CoV-2. And the prevention benefit of masking is derived from the combination of source control. That means everything what you exhale and personal protection. So inhaling for a new mask wearer, for the mask wearer. The relationship between source control and personal projection is likely complementary and possibly synergistic. Individual benefit increase with increased community mask use. So as more people have a mask, as better it is for each individual in this community. Therefore, don't be shy and just remind people if there are around you that they should wear the mask. And this, the last sentence, I think, is a little bit too positive that adopting universal masking policies can help a wear future lockdowns or anything. I think that will be not happen. Next slide. So here, the face mask function. Just to say the closed face mask, so the simple ones, they have some source control. So they can help that droplets in the exhaling are kept in the mask. But they are very bad in inhaling filtration the air. Searching the mask, you know, these are the light blue ones. They are very good in source control, but still bad if they function against or function for your protection. Then the respirator, these are this FFP mask or FN. So they have different names. I come back to this. They're very good for source control, but also good for your personal protection. And that's, I think, something we have in the past not so much looked at. But I think for your personal protection, it's very good if you can get this type of mask. And then the respirators with an exhaust valve, they're good for source control, but they're very bad for others. Because through the valve, you exhale all your droplets into the community around you. They're only used in high infectious areas where you need to definitely protect the people working in this area. Next slide. So this is the famous searching the mask or medically mask as it's called. And if you talk about protecting yourself against coronavirus, and it has, as I said before, it has not proven that this face mask can effectively protect you against viral infections. And you have to look at the side of this mask. There is not a good fit between the mask and the face. And this opening is a problem as well for inhaling as for exhaling. They are probably able to catch some germs before they reach your mouse or nose. And more importantly, they prevent people from touching their mouse or nose, and which most people do instinctually mean myself as well. And if you are already sick, such much can help to reduce the infection to others. So this is this mask which are good for protecting the others, the environment, but not as good protecting yourself. The next slide. So this is now the double masking makes Dr. Fauci, the famous science advisor to the US government, say double masking makes common sense and is likely more effective. And this goes back to the inauguration where everybody started to talk about it, not about the gloves of Sunday's only this one. So double masking, for sure, it's logical that a virus should have a tougher time getting through two layers than just one layer. Very close mask tightly on top of a surgical mask could provide even more protection. And I think that's a very good strategy to have these two masks. And so there is no gap between your face and the mask. And Fauci said, this is a common sense thing. And now the question is coming, how about three layers? Yes, three layers most likely are better than two layers. If three is better than two, how about four? And you could say, what about 200? But finally, you can't press because it's so tight that you can't press this. But also, if you see the right thing, if you don't have a medical mask, this double masking is a good thing. And the white thing, one of the best one are the taking a filter, which is made from your vacuum cleaner package. So they are very good in keeping these droplets away. So that's a good thing. Next slide. So now this was the two-mask. And now the weighs-up mandatory FFP2 mask in shops and transport open buildings. You have now to have FFP2 mask. And FFP actually means filtering face piece. And FFP2 is the name mainly in Europe. In other regions, they are called even KN95 or N95 or P2. So the fantastic thing with this one is that the FFP2 respirator is a tight-fitting mask, which creates a facial seal and filters both inflow and outflow of air. And they remove about 94% of all the particles in a certain size. But this is the size in a way of the aerosols. And so it's a much better protection for yourself. It's not only a protection as the close mask for the people being around you. So it protects yourself as well. But if you say here, tight fit over nose and mouth, but if you look at the imaging there, people with a beard are terrible. They should be not around you because there is no seal between the mask and the skin. There's a lot of gaps where the aerosols can get out and inside as well. So for beard people, there was a discussion here in Europe that official people working in medical facilities are not allowed to have a beard. The other imaging here shows because FFP2 respirator costs about in Europe, about between $2 and $5. So there's a lot of poor people in even in European countries. And there will be more poor people because of the lockdowns in future. So the government said, we need to make this mask accessible for poor people as well. And you see, even I got a voucher from the government that I can go to a pharmacy and I get then six FFP2 masks free of charge. Next slide. Because the price of this FFP2 mask is high, everybody is now saying many people can't go there and buy for every day new masks for the whole family. It will be quite an investment. So as you see the left image, it shows if you want to reuse your FFP2 mask, it takes about seven days. So the red spots are still the virus or the droplets. And it takes about seven days that they're going to zero. So one strategy could be that each person in the family has a mask for Monday, Tuesday, Wednesday, Friday, and so on. And takes on Monday. The Monday mask put it back there. Next day it takes the Tuesday mask. So you can then take this mask a couple of times without washing or without treating, especially because then there could be a problem there. Or as you see down, you need to have to put it in the oven for by a temperature of 80%. And then there are disinfected again and can use them again. But this process destroys the mask quicker than the other side. Next slide. So these are FFP3 masks, which is only used in COVID stations. But I just wanted to show you and see more and more often you see this type of mask available and they have a valve. And the valve is a problem for people around you because there's a fantastic protection. If you inhale, but there's no protection for the people around you by exhaling. So it is not anything which should be used in the community. And therefore, I think it's very clearly, if we say before about the cases being people vaccinated and becoming positive again, I think the mask will be gone. And the rules here in Europe, even if you are vaccinated, you are forced to have a mask because nobody knows when you become a carrier again. You can be vaccinated, but can be a carrier. And then it needs to protect others by having a mask. And I think that's a good solution. My last slide, please. So I like this statement. Sir Peter Medever, he won the Nobel Prize in 1960. And he said, no virus is known to do good. It has been well said that the virus is a piece of bad news wrapped up in protein. And I like this statement very much. And it will make clear that we live with masks the next years, absolutely as well as we do now. And we have to continue with all these activities. Thank you very much.