Vaccines: a double dose with Professor Brian Cox | The Royal Society

good evening everyone and welcome to tonight's event we call

vaccines

a

double

dose

is part of the ongoing series here at the real

society

uh analyzing and looking at the scientific landscape around the kobit 19 pandemic in january in our first discussion we looked at the early stages of the vaccine rollout and tonight we thought we'd take a current view to reflect on the vaccine rollout but also to take a more global view of the vaccine rollout and see how

vaccines

are being delivered across the world. world now i'm the

professor

brian

cox i'm the

professor

at the

royal

society

for public participation in science and one of my jobs tonight is to submit your questions to our panel so you can submit your questions by going to solido.com and so on your web browser type solid.com and then type the code v605 to make it v605 you can also follow the slider link in the video description and you can also upvote questions and which i found very helpful in previous events s o I have an idea what questions you really want me to ask the panel so they can ask them and also vote on the questions they think are interesting and would like to be asked.

We also have subtitles tonight, you'll see. a link at the bottom of the video bar that you can click for closed captions and you can also tweet of course we have a hashtag covered in science if you want to do that so without further ado let me ask the panel to be present thank you you are very much

brian

my name is salim karim i am the director of caprisa the center for AIDS research program in south africa and i am the professor of global health at columbia university hello and um i am katrina lithgow i am a researcher at the university from oxford and i work on the evolution of viruses so previously hiv and hepatitis c and now on sarsko v2 which is the virus that causes covid19 good evening i'm chris whittie i'm the chief medical officer for england and she's plant santa advised health and training I am an epidemiologist and infectious disease clinic hello my name is wendy barclay I am a professor of virology at imperial college london and have always been interested respiratory viruses that cause pandemics mainly influenza so far but now sarsko v2 thank you all now to get started um you can also ask solido questions but we also have a couple of surveys that i will be presenting throughout the evening and also a word cloud that we found it really very helpful in the long code discussion above because it gives an idea of ​​how you feel about particular issues and I can also put that in the panel and just to test it the first if you're going to solido is um we ask you to say in one Please tell me how you feel about the kobit 19 vaccination program in your country so I think it would be particularly interesting to get a sense of how you think the vaccination program is going so just one word and I'll get to that in a bit. moment like t The word cloud builds up so that's on solido um but I thought I'd start by getting an overview from each panelist about the release about the vaccine and how's that program going and I thought I'd start by selling and asking um specifically that question, what's the landscape for vaccines like right now?

When you think of vaccines, we usually think of the years and years it takes to make one. to see how quickly we could make a covert 19 vaccine. And if we look at the current landscape, there are now over 200 candidates and exactly 124 are now in clinical studies going from the phase one study to phase three. we have eight approved vaccines that are in widespread use we have another six that are limited and limited approval but, in general, part of the reason vaccines are so quickly available is newer technologies, particularly mrna a and viral vector vaccines alive and among the four different types of vaccines, those are the two types of vaccines that have been at the forefront and now have been most widely distributed so far about a billion

dose

s of vaccines have been administered worldwide thank you very much thank you sam that's pretty amazing actually 124 currently in clinical trials it's because especially here in the uk unless it's for wendy we've heard of probably two or three of those so wendy can you set the scene now describe the situation here in the uk United, yes I mean here in the UK so far we have only immunized people with two types of vaccines or two brands s if you like one the mrna vaccine the fisa vaccine and then the oxford astrazeneca combination adenovirus vector vaccine but there are others on the go if you want there are other opportunities to come and for example the vaccines of Inactivated virus and other versions of both the mRNA vaccine type and the vector vaccines may become available. ilable as we go but actually most people who have had a vaccine today in the UK would have gotten the one from Oxford Astrazeneca because we've used a lot more doses in the UK than Pfizer um and you know I'm very lucky to having such early access to those two vaccines and, chris, what are the main issues around vaccines now?

I thought it's used internationally to look at word clouds because people don't. audience maybe it's that there really isn't a problem in most people's minds i mean the big words are relieved confident hopeful proud positive optimistic uh fantastic so people clearly think that there really are no problems but there are problems in the UK around vaccination implement, so actually, maybe in the context of the whole world, well I think the thing, um, that maybe I'll focus on is how do you actually implement vaccinations, um, because it settles down when you've already talked about the different types of vaccines and um d different diseases you actually do this in different ways so uh with um covid because it's a disease that in the UK context has been very dominant in terms of diseases really serious and mortality uh older people so 86 of the people who died were over 70 years old. 70 or those who took care of them right away, we've done a vaccination schedule that started strictly based on age, aside from those for some very specific pre-existing health conditions and went down through the ages, but people on the higher end of the age are the people who are most likely to die from covid or the people who are most likely to end up in intensive care or at a slightly younger age in the hospital in those people, maybe in their 50s or early 60, but much of the transmission of this disease occurs with people who are younger than that, so our current vaccine program is very successful in reducing the chances that, in the long run, people will go to the hospital and die in which it will not have the same effect, but it will. o As we go down the ages, the impact on transmissions is so great that much of the transmission is from people in their late childhood years, adolescents, and particularly young adults in their 20s and 30s, and that it is in complete contrast. to some other diseases, for example, measles, where you really need to vaccinate younger people because a lot of the damage is done in younger people, uh, the last thing is to recognize that, um, some of the serious symptoms, for example, a group of things that are currently called covered for a long time can happen to younger people and that is one of the reasons why it is essential that they are also vaccinated so that both contribute to transmission throughout the community, but there is also the risk of getting seriously ill. uh even if uh in terms of long term disease uh even if not actually uh they have a very high chance of dying now this will be slightly different in different countries and the bottom line What I would say about this is that it's really important that we look at this as a global problem, not just a uk problem, although obviously, at the moment we're just concentrating on the uk situation, the vaccine runs away with the vaccine. variants are another problem but i think you'll get to that later brian yeah so i guess to sum up what you said i guess a tendency to look at deaths which are extremely low in the uk and think hard about the problem is on its way to being sold, I guess what you're saying is that that doesn't reflect general immunity across the population because we have serious problems potentially with younger people who wouldn't show up in those statistics necessarily exactly and if we suddenly dropped all the current social distancing stuff that we have the rates would go up very quickly if we did it right away because there are still a lot of people who are susceptible who could tr respond and there are a lot of viruses around for them to get infected so we should look at this already that we are headed in the right direction, but there is still a long way to go, even in the UK, which is a long way ahead in its u vaccination unfortunately many other countries are much further behind right now um katrina um what are the unknowns here and chris has touched on some of them perhaps but in this context of the global vaccine program what are the what are the unknowns , yeah, largely what Chris said earlier, but to me, the key unknowns to what extent vaccination will actually reduce transmission because that really affects our predictions, um, going forward for future waves and whether, for example, immunity and protection may be decreased. through time, for example, and then it's about how the virus could evolve to escape those vaccines and there are many different ways that we can imagine the virus escaping escaping from vaccines could um that w I'll allow people to allow that the virus will infect people who have already been vaccinated, but it is to what extent those people will become infected if they have been vaccinated if there is an escape variant.

Will the disease be that serious? Know? Do we worry that much? if people get infected but the disease isn't that severe and then to what extent if you're vaccinated and you get infected with one of these new variants you know you're going to continue to pass that on to other people so these are really key unknowns that they really affect how we will see the progress of the virus in the future so thanks for mentioning new variants now so they are very closely related to the progress of the pandemic around the world and so in this kind of section on the that I would like to talk about the global vaccination program maybe you could talk or ask sales initially um how should we and how are we approaching the global vaccination program and um related to that why is it so important So when we look at the global situation, the first vaccine was delivered around the second week of December, since then we have been vaccinated with around a billion doses, I think the great concern and l What worries me the most is that of the billion doses that we have said that seven countries account for about three quarters in terms of salim you mentioned it there I guess the main contrast between approaches in the world is one of the numbers, the science said maybe seven countries that have been extremely successful and the Rest catching up, but is there any difference in approach around the world other than sheer vaccine availability? point about you know this is something we need to look at as a global issue and where we should be aiming for global coverage huh some sort the way different countries have tended to prioritize citizens has varied depending on what they were aiming to achieve mainly some countries have prioritized, for example, vaccinating those who provide social services, I mean in a broader sense, police, teachers, doctors and others, uh, some have uh tried to see how we could actually interrupt transmission, but I think the uh point that Katarina made before that we don't really know the impact on streaming, I think that's something we need to keep in mind. it certainly narrows it down but how much i think is uh still uh a bit confusing um so there have been a lot of different approaches different countries have tended to use different vaccines and there is one vaccine that uh is currently in the works the jansen or johnson johnson vaccine you only need to give one dose instead of two doses and the final difference is that for those who need to give two doses it's different t countries have taken different approaches on how long to delay so all manufacturers suggested fairly short periods of 21 days for example the UK view because we were very because we had shorter vaccines every vaccine short country we were going to delay the second doses because I thought the maximum public health impact would come from delaying them so we chose 12 weeks and that mainly meant that we could

double

the number of people in the first period that we could vaccinate in order to be able to increase coverage, there are some theoretical reasons to think that a longer delay maylead to a better immune response actually, but the main reason was actually just to increase the number of people who got initial protection, which is the majority protection, different countries have taken a slightly different approach so that, oddly enough though, overall countries are now moving to increase the delay between doses rather than decrease it.

This is the direction of travel now, yeah, I figured out the US and I've specifically taken that, haven't I? I think I've read and a number of European countries are now starting to consider this, katrina, I know your background in part is in modeling the epidemiological model and the spread of the virus, so we've touched on the idea that it's a clear message, actually we haven't touched on you that you have to deal with this pandemic globally and you could comment if we don't if we try to take this view that we're going to be a single country focused vision what would be the consequences as far as we can tell given what we know in modeling?

The consequences for the UK really come in terms of, um, the variants that would be coming into the UK from travelers for whatever reason, people travel and the variation in the virus coming in will be kind of a reflection of what's circulating. in the countries that people are coming from so of course if there's a lot of viruses circulating if we're seeing heaven forbid even more you know variants we really have to worry about then they're constantly coming to our shores and and and the like and the kind of bigger that flows onto our shores the bigger the chance that one of those um infections coming in could seed a big outbreak um so it's really um you know, uh, you know, I think everyone on the panel here, we would really like to see you know about equitable access to vaccines but at the same time you can think about that you know from quite a bit you know a personal kind of selfish point I also believe that by protecting the world we also protect ourselves.

I think it is fair. I saw it. like almost like a wildfire that you see emerge in an area initially with a modernist style, Spain I guess, and then it just spreads inexorably no matter what you do, I mean it really is the message you really do. gotta eradicate it pretty evenly mly all over the world otherwise you wont contain it i i yeah i mean i think i think kobe is with us to stay but the more we can yeah keep it down less sparks if you want to keep your analogy of that fire and then it's the few, the fewer than that, those kind of sparks that we need to try to chase down and eliminate, and maybe I can also add that you know the other reason to keep the number of viruses down is because how many the more viruses there are in the world in total, the more evolutionary space, as we say, the virus can explore, so there will be a better chance that a mutation or combination of mutations will be created if it wants to, since the virus makes its mistakes and Find that space. that can escape a vaccine so it's also a numbers game it's not just about keeping it out of one place it's about the total amount of virus that is replicating around the world and keeping it in check I think it's a good introduction actually the next one the section where I think mutations is I'm seeing the questions is one of the things people are most concerned about so we'll get to that in a bit I should just say that we have our first live survey, which is interesting in the context of the global vaccination programme, we would like you to answer the multiple choice survey questions, but who should be responsible, i.e. individual governments, the world organization of healthcare, pharmaceutical companies, g7 nations or any or all of the above, so I think it would be particularly interesting if you just gave your opinion on who should be responsible of coordinating a global vaccination program and with that, actually, he says that all of the above seems to be oh, the world health organization seems to be the two that are there right now in the survey, um, maybe I'm saying seriously, maybe it's a question generally for the panel before we get to the mutations in that survey, who is responsible? one specifically responsible is the framework established at this time.

Would anyone like to answer that question? Maybe just make a quick comment. It is a moral and ethical imperative that you know that if in one country there are low-risk youth vaccinated while in most of Africa the highest-risk health workers have not been vaccinated, that is unconscionable, unacceptable, and should be unacceptable to the world, but that is the reality, that is exactly what is happening and now we are going to see in the United States that they are lowering the vaccination age to 12 years. while in most of the rest of the world we haven't even received doses for healthcare workers, I think that's also an integral part of the challenge and, to me, it points to the real challenge in the way that vaccines are currently being distributed, which that the market allows. t forces you to play the game if you have money you buy you get if you don't have money sorry go to the end of the line now the world health organization tried to address this by joining sepi and gabi and creating an organization called kovacs and the basic idea of ​​kovacs was to buy wholesale and then distribute fairly and when you think in its most fundamental form it's a pretty good concept for fair distribution the challenge arises because there are a lot of countries that just can't afford vaccines and therefore Therefore, donations must be made to receive less that, but the biggest problem was that the countries that with more financial influence jumped the queue are willing to pay higher prices that they negotiated with the companies and so Kovacs left at the end of the cola so kovacs is distributing vaccines after most other countries have gotten them because they were rich so I think market forces have shown they have flaws, so we need them.

I have a centralized approach and to me the world health organization has the moral standing and the responsibility for global health and is very well positioned to take this on and they need to create an organization like covax but with more influence and more ability to buy vaccines and get them out faster so thank you in terms of um we've heard the arguments for the fact that we need to vaccinate around the world it's the only way to get this pandemic under control. In terms of mutations, one of the most popular questions at the moment that's been asked is, related to that, are there variants already in the UK that the vaccines don't protect against?

Maybe I could start with Chris and then I'll have to have a first try, but this is an area where Wendy in particular, I think she could add a lot to, um, I mean, the short answer is we're not in the early stages of understanding how different vaccines work. interact with the different variants so we don't have absolute certainty about this, the b117 variant, which is the one that was first described in the UK, often described as a UK variant, we're confident that vaccines that at least they are currently available in the uk it works against that for practical purposes in terms of the other variants that have come from other countries uh in terms of their first description to be clear that is not necessarily where they arose and i will refer to them by their uh than the country in which they were raised simply because that is what most people understand.

That doesn't seem like with most of the available vaccines it would lead to complete vaccine failure, so we think it probably provides some level of protection against severe disease and mortality, but it's likely to reduce the effects of the vaccine in milder diseases and disease transmission which would be, I think, where we would currently be and then there are a number of other variants that are somewhere in the middle, including one that emerged in brazil circle the p2 variant and then recently they're described several variants in India that we don't fully know about yet although I think they probably fit in the middle as well so I don't think there is any variant that at this point we feel vacuuming won't work at all but there is a sliding scale from situations where the vaccines work just as well as they do against the wild type, the original one first described leaving China and then Europe , to the one at this point that seems most concerning about the escape, which is the South African bones that we have here in relatively small numbers, obviously uh, saleem has a lot more experience with this in south africa, there's a lot of, uh, in the south of africa actually there's a lot in various other countries around the world but wendy might want to comment on this uh she's really something she's very adept at um well thank chris for saying that um i think that i totally agree with your summary, uh, what about a vaccine? predicting protection against transmission is a difficult task, um, and that's what is lost first, since as the type of match between the circulating virus or new variant and the vaccine strain diverges, it will be the transmission whichever slows down first and then it will be symptomatic disease and then eventually you will meet hospitalization so the good news is the very direct answer to the question is no there are no variants in the UK at the moment that we believe against that the vaccine won't work to protect people against severe illness, hospitalization, and death because, um, you know, the gap between all the variants and the virus that we started with isn't that great so far, I think what's in The back of all our minds is that this is an RNA virus and that there is evidence coming from people frantically studying some of the other seasonal coronaviruses that we know have circulated among humans. humans for a long time that these viruses probably drift in the same way that we know the classical influenza virus drifts and over time, over the years, it's possible that this virus could accumulate more and more mutations that change more and more um parts of its surface, so right now because we all do what's called a polyclonal response, a change here and there in the virus means we still have antibodies that see the other parts of the virus that we don't yet they've changed, but when you get to a point where the virus has changed in a number of different places, you'll start to erode that polyclonal response. we've done so I think it's something we need to be very aware of and we may see variants emerging with varying degrees of distance from the first virus that came out but so far nothing that completely rules out vaccines and the other thing that I What I would like to say is these vaccines are amazing as Saleem started they are really great vaccines which in particular I think the mrna vaccines produce large amounts of antibodies and that gives you a lot of breathing room if you want because it's not that the vaccines They don't just work, they work pretty well, so even if it's a bit of a mismatch, you still have a little bit of room there where the vaccine will have induced enough antibody. to continue to protect at least against symptomatic illnesses yeah I wouldn't say like katrina because I know before kobe does his flu experience and um so how does this compare in terms of you know the flu strategy that everyone will be familiar with in the UK at least? with the fact that you have the flu shots and we made a decision at the beginning of the year about which flu shot to make and so on, how will this ultimately compare and then maybe a deeper question is what do we know about from the comparison between the mutation rates of viruses and how similar and different influenza is covered in this regard, yeah I mean our side is that um uh saskop2 has a low mutation rate so it evolves more slowly. than many other RNA viruses and, but I think it's really interesting that analogy that you make with influenza because we see a kind of evolution of influenza, we call it drift and shift, so you know that from year to year we see this type of small changes and then all of a sudden you'll see a big change and that's what causes a flu pandemic and so it's interesting to think of um sars cop2 that way because all these variant concerns that we have in the UK have actually, been a lot of mutations that really puzzled everyone at first it was really unexpected um and it's probably an increase in a single individual and then and then that triggered, you know, a new chain of transmission s or potentially we could think of it as kind of a change, you know, a big change, but then we're going to have all kinds of these little changes like a mutation here and a mutation there, which is much more gradual and so I think which I mean it's a virus that's on a brand new host um so it's really anyone's bet as to what direction it's going to go in the future and there's a question that maybe related was something Wendy said at reality um aboutwho knows mrna vaccines in particular felt it had quite an amazing effect there are a lot of people interested in the question about the differences between the in the uk anyway the pfizer and the modern vaccines and astrazeneca the the um anyone I would like to comment that what we know about the relative effectiveness of these vaccines and also perhaps in relation to what Wendy said that the potential for a mutation to evade the vaccine in some sense is the one that we don't think is most likely to be evaded or a someone would like maybe that's too speculative, but the initial question about effectiveness, what do we know about the data about effectiveness?

Well, I'll try this first because, um, there's the test data, but test data is always a little hard to compare because, uh, people test in slightly different ways. ways and then there is the real life data that we have seen in terms of effectiveness in different groups in the UK and we have the largest amount of data in the UK on people who have received a single dose of az adene uh vectored virus uh um vaccine or pfizer one and um for our own variant the b117 variant uh the um that is now dominant in very large parts of the world uh unfortunately um the uh though there is some difference around 21 days my point of view is that by the time it arrives at 35 days with a single dose the difference between them is really very small these are highly effective vaccines uh we have good data from around the world showing that a second dose of pfizer substantially further increases the protection that pfizer produces we're starting to get that vaccine data az it's a little less it's a little sooner because we implemented pfizer earlier huh for practical reasons um but i think you know the key to say is that these two vaccines and I would extend the same to the modern one that we are starting to use in the UK appear to be highly effective against the mainline variant circulating in the UK and also relative to other other drugs and other vaccines very sure these are the risks-benefits in terms of being protected huh to have side effects with these two types of vaccines huh it's very favorable for the vast majority of people and actually you mentioned maybe sally could ask you why I think Chris mentioned who obviously has a lot of experience in southern Africa, for example, what is the situation there with the different vaccine technologies available and how effective are they? t the dominant variants in southern africa yeah right so you know mutants are mutants uh mutations in uh viruses pretty standard for all viruses and most of the mutations we don't really care about because they are so minor and we don't They do really made some change but South Africa got a wake up call in December when we discovered a new variant we call it 501y v2 or b1351 just a bunch of numbers but basically it's a virus with three mutations occurring in the key part of the virus . that it adheres to the human cell and there were four things we were concerned about when we first described these values, the first was whether it is more transmissible and now we have pretty good evidence that it is about 50 percent more transmissible and similar to the similar type of higher transmissibility of transmission as what has been described for b117 in the UK and probably also true for the p1 variant in Brazil and also probably I mean the evidence is too early still in India to make a definitive comment , but it also seems like it's more transmissible, in fact it needs to be more transmissible to dominate the way a virus evolves to adapt better and be able to spread faster.

The second problem is if it is more serious, that is what we are. we were really concerned it turns out that in south africa the evidence we have now is that it's not more serious but we saw more deaths and those deaths piled up at our peak so at the peak the hospitals were full, they were too busy and therefore So the quality of care was affected and therefore we saw an increase in deaths but the virus itself is not causing more severe disease per se the third is if it evades natural immunity and here we have evidence pretty good because this trial was done with people with past infection and people without past infections: we look at the new incidence rate of infections and the answer is yes, the b13 351 or 501y b2 variant partially escapes past immunity, so if you have been infected with a virus before you are not fully protected this time about half of the people who were exposed who had a previous infection were infected again e, so we saw three infections occur and then our biggest concern is whether these variants escape vaccine immunity and we have some pretty good ones there. evidence from four vaccines, so if you look at, for example, the astrazeneca vaccine which was found to be 70 per cent effective in the UK, it was only 10 per cent effective against 501y v2, but that was a study that focused on mild disease we don't have clinical evidence on severe disease if we look at the vaccine called novobax which was 89 protective in the uk but only 49 protective in south africa on the other hand the johnson and johnson vaccine showed quite similar levels of levels fairly consistent protection at about 62 to 66 percent in the US in Brazil against the p2 variant and in South Africa against the 501 yv2 so it shows similar levels of efficacy across all these variants and if we take pfize r because of that the trials of the fisa vaccine were also done in south africa, it was shown to be 91-95% effective the first time, based on the data in south africa, it is still 100% effective, but it is a small component of the study that we have had no infections or clinical infections or sub or asymptomatic infections and those vaccinated with the fisa vaccine despite 501 yv2 infections in the control group, so these vaccines show some differences in ability to neutralize this particular virus and that is one of our big concerns about these variants because it is a harbinger of things to come, we are going to look next at another variant that is more effective at escaping vaccine immunity and I think that is our big concern right now i think most of us would want to believe and think based on indirect evidence think almost all vaccines are very good against serious diseases right now we don't have solid data on all the different vaccines but it seems that that is the case, but the next stage will be whether we can really prevent infection to prevent viral transmission and therefore the asymptomatic disease and mild disease will be important for us to control with vaccines in the future. online and so we're going to see our vaccine needs change right now vaccine needs and let's prevent deaths prevent serious disease and in the future we're going to try to control this virus so it's going to be very important what role variants you play in this , there's actually a question that came up related to what Sally had said there, maybe someone would like to take it up, which is is there any since there's a variation in effectiveness that appears in the data against particular variants for each vaccine, if there are any plans to mix up the doses to give people a zad and a pfizer or a modena or whatever is there any reason to believe that t That would be helpful and that's when you plan to do it so there's both I have a primer I mean I think so in the UK we are at least doing trials where we do exactly this where we mix different vaccines together and see if the immune responses are better but res or the same and also if there are any side effects that you didn't expect from them and that's also important obviously from first principles so from other vaccines mixing vaccines is usually a good idea but we didn't have data on this so which the reason right now if you've had an az first osu to nasa secondary then you get and they said pfizer first gets it first a second those are the combinations we actually have scientific data for as we get more information we will have more flexibility and it is quite possible that actually by mixing the doses, you will have a broader level of protection and then eventually what I think we all anticipate is that we will end up with what are called polyvalent vaccines , vaccines that currently ly cover several different types of covid and hopefully will really protect against a wide enough range to go back to Saleems and Wendy's earlier points and indeed the points from Katarina they not only protect against serious diseases but they prevent against symptomatic diseases and uh transmission uh potential so the long-term goal I think will be to have a much broader range of mixing different vaccines and the same vaccine with several different types yes, just i wanted before i get to the next poll i just wanted to ask a question because i know before we went on the air katrina was speaking from personal experience about these questions i could never ask you and that's why some people experience worse symptoms afterwards from the az as a zed chad specifically in question, but we could expand that to any job. than others and then it seems that if people have not felt good about Kobe 19, then they have a worse reaction to the jab, so what do we know about that situation? if you've had the disease and reactions to the pricks katrina that was yes so i was the one who spoke from personal experience that um you know i was self diagnosed with cobia in march and then when i when i was lucky enough to have the vaccine um astrazeneca um a couple of months ago I really um you know I lay down for a day really and so uh yeah so I was reiterating that question to what extent um what is the effect of type of prior infection and that and that was my question to Wendy actually my answer to that question is that now there is pretty good evidence that people who have covered and recovered and have already seen those immunogens once make a very, very strong response when they get their first dose of the vaccine because the way you know these vaccines work or the way your immune system works is you prepare and then you boost and the preparation sets the stage and tells your immune system what to do r and then when it sees the same antigen again, it generates a huge response and we see that a lot in healthcare workers who have been a part of many of the studies that have gone on to look at the immune responses that vaccines have produced. and we know that, unfortunately, you know that in the first wave of the coveted pandemic, many healthcare workers acquired the coveted infection and therefore had an immune response to their own infection and then when we immunized them. with the vaccines they get a very strong response um compared to their colleagues who were not previously infected and got their first dose of the vaccine and had a good response but not as good as the others um I mean my answer to why you know that sometimes you feel pretty bad is that the immune system is very energy rich and hungry and it takes a lot of work to generate an immune response and also the way that it works is that there are many cytokines and chemical chemokines that are a part of our immune system that makes it work properly and it's those same chemicals that make you feel like you have mild aches and tiredness and sometimes even a fever, but usually that's a sign that your immune system is responding very good. strongly to the vaccine that they gave you so I don't think it's surprising that you experienced those kinds of symptoms if you will from the first dose and I usually tell people to cheer up because it means the vaccine was working and you were giving a very strong answer, so I think we'll go to the next survey, which is a question for everyone, how do you think we can ensure fair and equitable access to vaccines?

I guess it's in a sense yes and you can put in a word so it's going to be a word cloud so it's quite difficult you're actually challenging yourself how do you think you would ensure fairer national access to vaccines in a word? w Well that's the poll, well as you're playing that poll on that worldwide word cloud, there was a question that a lot of people are interested in, um, and it's a question from the UK perspective, but it's related to the different variants and effectiveness. of vaccines and the question was were we lulled into a false sense of security and because you clearly know you all see the pressure it was lovely to open up the borders people wanted to holiday abroad to europe and beyond and so on that's right this located in the uk because at the moment the disease seems to be on the low level if you look at the statistics anyway people feel safe because they got vaccinated which leads to a false sense of security particularly with reference to the international travel who would like to i didn't address it to anyone specifically i mean i mean i can i can answer thatfrom, um, you know, a modeling perspective, um, and you know right now we're, you know, we have the, you know w this famous arnold number which is you currently know less than one and well you know it's very low of anyway and that may, as you say, make us feel safe, but it doesn't take much for that number to increase for they're not to increase, it doesn't take as much openness and we saw that after the summer holidays and so it's a very careful balancing act and i'm sure chris would agree between opening but keeping that r value down and he's balancing it with the um with the number of people being vaccinated and then he has to think about new variants and if those new variants are more transmissible so that pushes arnold's number up which means you need to vaccinate more people or maintain other restrictions to make it feel like we're in a very happy place and in the uk right now So, luckily, we're in a very good place, but you know I think history has told us that it doesn't take a lot, um, to get to that tipping point and for infections to start growing very rapidly, chris, do you would like to comment on yes and i think ok i mean the first thing is uh i think people in the uk and this is true in a lot of other countries but the uk is where i know best they have been really notable how patients have been and how pragmatic they have been about it. and if you look at the polling data, the vast majority of people have actually said it absolutely rightly, they've said how long it's going to last, they've actually judged it with remarkable accuracy, they've all agreed that it should be done. far fewer know fewer people and that's still the case today the reason the rates are low is a combination of people knowing fewer people and not taking risks and the vaccines but it's that combination in one , either one of us alone wouldn't have gotten us to the place uh the lucky place we are at right now so I think we need to take it steadily the point about vaccines is they take more and more of the heavy lifting and hopefully we can whittle this all down bit by bit until we get to the point where we're living a life that's basically back to normal like it was before the pandemic but people are being sensible living stable that's the way that we're trying to take and I think I think most people agree that it's the appropriate way to do it. you set things steadily uh at the rate you can do it in terms of people traveling abroad there are two separate sets of risks and I think they are much more different harder to calculate than the other one the first one is if a country is has a very, very high rate and another country has a very low rate, then there is a significant risk of importation in either direction and the UK has been at some points a net importer of vaccines and at some point a net exporter of viruses depending on where we were in relation to other uh countries, the much more difficult one is the one we talked about in the previous section, which is the risk of importing a variant that is more transmissible than ours or that can escape Ape vaccines could cause significant long-term problems and the problem here is that these are high impact, low probability events and are much more difficult to model and predict on a scientific basis than e those where you can tell how big the impact is. will have this because another country has a slightly higher b117 transmission rate which is what we currently have so that's what makes the international issues really much more difficult and I think a third thing of course is people often travel through more than one country and that makes all of these travel related issues really quite difficult for legislators in all countries.

This is not a UK problem in particular, this is a global problem. Looking at it, it's yeah, it was actually interesting, so how can we show up here and can you access it? Share collaboration Who again? older age particularly from all the panelists this is a global issue seems to be shared by our audience at least and requires a global response and the latest i'll just say the latest um poll you can start to see actually i'll just wait a minute, I'll let you ask another question before I go to the last poll, so we've got an interesting question that we've covered before actually, but a lot of people are interested in it, which is maybe I'm initially asking Wendy and how could developments related to the Kobe's vaccines change its ability to tackle other infectious diseases.

So will these technologies have a more distant impact? anything is that vaccines work and we can make them pretty well and modern technology has great routes to make vaccines and again thinking about the experience with influenza where we kind of race against time every year to try to best guess what flu strain is going to cause most of the disease in the winter and the vaccine manufacturing process takes six months and you have to try to pick a strain in February that you are going to put into people's arms in October actually So, with some of these modern technologies, you can probably respond a lot faster and also with a lot more precision because you don't need to grow the virus in the eggs or in other ways that might affect the efficacy of the vaccine, so I'm very hopeful that that, not only because of the rapid responses to future newly emerged viruses, but also because of the types of vaccines that we routinely deliver year after year, some Some of these new technologies can really start to push the boundaries and improve our vaccines. a lot of people are interested in whether you actually mentioned it, but at what point do we make a decision in a country like the UK or the US to prioritize and other countries given what we've said about the need for importance to do that in rather than chasing diminishing returns in a particular country say the UK so there's no simple way to solve this because it's as much a political problem as it is a scientific problem where you know I can't see any politician saying oh, You know, we have several million unvaccinated people in our country, but we're going to send the vaccines somewhere else, that's going to be quite a difficult thing to do, but you know that's part of people wanting to protect themselves, but also part of the challenge is the kind of Donald Trump-like view: you know me first and I don't care about anyone else and you know we've seen a little bit of both play out in the vaccine world, um, I think for me, the p The highest priority should be to try to vaccinate the world, the two groups in the world are a priority before we do anything else and the first is the health care workers because they have the front line that they have. such high rates and they are the most needed when we have a surge and they are the first to get infected and have to go home just when we need them all in the hospital so vaccinating healthcare workers is very high the rate of return and then the second is the elderly you can take it ie above 60 or whatever cut it but those two groups I mean co-obilities etc play a role but those two groups really should be all countries I figured that by the time we get to know two billion doses that each country would have vaccinated at least those two groups because after that the returns become much less and when you start to go down to 30 years and 20 years you already know the return is much lower, so I think once countries have vaccinated the elderly and health workers, some essential workers in countries are also counted as important, like school teachers etc., but once they those groups have been vaccinated, so I think you should think about donating a certain proportion of vaccines or helping the kovacs and getting vaccines to distribute to the poorer countries which I think would be a pretty equitable thing if it's really practical and politically feasible for the politicians to do that in a country, that's a different matter, yeah, and actually, let me direct you to the closing poll, we've got about five minutes left, which is, um, on a scale of one to five, uh, one is the lowest five, the highest five, and how worried you are. about the different variants of the virus and possible third or future waves within your country, um, and if you want to vote on that, um, then, yeah, well, people are worried about that, um, related to that, actually the question here about the awesome booster schedule I know this is pretty useful UK specific but I'm guessing it will apply to all countries and the question is will that schedule we hear about specifically cater to the new variants and if it is as well as? going to implement in the fall booster program um maybe i guess this question to chris was really uk focused initially but anyone who wants to contribute please do well from a uk perspective. for potentially wanting to do a booster program, but probably for a select group of the population, in the fall, one of which is what we expect and see some evidence that, in particular older people or people with some reasons for where your immune system is damaged. whether from drugs or other diseases, they will lose their immunity faster than other groups, and at the same time, they are the most vulnerable group, so there is an argument for simply boosting their immunity, leaving aside the variation in general. uh, the second reason, uh, though, is one that, uh, Wendy in particular, but others have made about the fact that these are such, uh, that if we can get a sufficient immune response, it will overwhelm a variant, even if it's not very good. designed so that your two options are either to go for an older vaccine that we know is on the shelf actually boosts the antibody system and therefore will help protect in an indirect way from the variant or a new newly designed vaccine variant in I actually think the chances of having a newly designed new vaccine variant that is effective against major variants, particularly the one that was first described in South Africa, but before Christmas are pretty small now obviously we're all doing our best to speed up those processes, but I think realistically uh, that's the case and so it's probably going to try to essentially use a rising tide, uh, raising all the boats, uh, approach, uh, with some of the older technologies.

It may not be the vaccines we're currently using, but some of the older technology, but in due course I hope we'll use variant vaccines around the world and it may be the ones we actually adapt to particular geographic areas. one possible possible way that we are going to look at things in the long term thank you very much we are almost out of time but i want to review a bit at the conclusion of the discussion is there one final question i would ask i would like to ask if i could keep it short but for everyone on the panel, maybe start with Wendy and move up the panel and the final question is what the future of the pandemic looks like from her point of view and the secondary text is will the vaccines be the end of kobe 19?

So in my opinion, we will not eradicate this virus, it is so widespread around the world and vaccines do not necessarily completely prevent transmission, so I think we will live with the south kobe derivatives. 2 for a very long t ime and as I mentioned earlier there are four seasonal coronaviruses that probably jumped from an animal source and caused a pandemic in the past of humanity that we already live with and this is going to become a fifth um hopefully we learn to handle it um and that as time goes on and people have seen it before in early life maybe they won't get as sick as when this virus first broke out in the human population so I think the long future term is good but there is a lot to do in the middle term katrina yes i think i am just reiterating what wendy said i mean we have only eradicated two viruses from the planet through vaccination which is smallpox and rinderpest , and i just can't see us um being able to do that with um covid but as wendy said i think we should be very optimistic about our abilities to deal with it huh chris i think what this shows is the strange Ordinary power of science to address infectious diseases and we have addressed it in this pandemic epidemic so far with vaccines and some old drugs will come new drugs we haven't talked about that but HIV where saline for example he's so experienced the drugs are really the backbone of this we'll get them we'll get them new vaccines but long term I hope this becomes as Wendy says a much milder chronic disease overall probably with spikes seasonal, and from time to time there will be enough of an antigenic shift that we actually have another problem. that we have to respond in due time and it will probably come at the same time as the flu and various other infections of that type, but in the medium term I have to saythat the outlook still looks pretty bleak around the world and it really would. i reiterate i think all of us would do what selena said until we have a situation where we have induced immunity and those who are most vulnerable around the world will continue to see really significant morbidity and mortality from this virus so i think if i have a five year view the combination of time and science is on our side but its not going to completely go away according to the other speakers on this any time soon i think we need to look at the next 18 months and say we really have to make a global effort on this and just to clarify something that you said there about the return of fairly significant spikes at some point in the future is that in the sense of peaks of influenza pandemics it's not, uh, you're not saying we're going to have the uh disaster again yeah one of the little problems I have is every time I draw a parallel with the flu people say I'm saying it's like the flu flu is not like flu this is a virus it is very different from flu but there are a few things that are probably similar and one of which is you have good years and bad years if you think about flu in the UK and this is without a major antigenic shift, you know?

On average we'll have seven to nine thousand people dying a year in a fairly typical bad year, maybe 20,000-25,000 people dying if we have a pandemic with a severe flu it could be much more than that and in 2009 we had a pandemic with a much milder flu, in fact, it was relatively small numbers, so it's very variable over time and, you know, covered by the reasons, uh, that katarina and wendy that we were talking about earlier probably won't behave like we does the flu but I expect there to be variability year to year and within year between seasons that's the expectation with respiratory viruses and I think that's probably the end point kind of end point for this none of us know it's a species of educated guess based on other infectious diseases but i think that is the most probable right now and stalin the initial question just to remind you is what does the future of this pandemic look like i will make three points i think the first one i would like to agree with what wendy and chris said you know this virus is not going anywhere which we will not be able to eradicate for many of the reasons they mentioned but also because it infects both domestic and wild animals so it will continue jumping between species, so I think we will have to learn to live with this virus for the long term.

The second is that I think there is a reasonable chance that we will see the creation of new variants and I think that vaccination will put immunological pressure on the virus to escape and in those who are immunosuppressed who have been vaccinated and have generated these antibodies we can see founder variants that we have more ability to escape vaccine immunity and our ability to make new versions of the vaccine as modern has done and just reported their results on their new version of their b1351-based vaccine that as soon as we make them and distribute them is probably going to be out of date because there's a new variant out there, so we're going to look at those kinds of challenges and the way to deal with that is to remember that we have a whole set of prevention tools. x not just the vaccines, we have to find a way to use that combination of prevention, some restrictions, not the ones that affect our economy too much, but some personal behavior changes along with the vaccines, I think in combination we have a very good chance of achieving it . know to a situation where we can do most things normally and then the third point I want to make is, like chris and katrina, I'm pretty optimistic that we're going to see the generation of new technology that I've been involved in hiv research now for over 35 years and i saw from a terrible situation where people were dying and i mean my wards were full of patience and i couldn't do anything for them to a situation where antiretroviral treatment changed the game completely and now we've never had an hiv vaccine and the prospects for a vaccine seem a little long but we've been able to reduce transmission we've been able to reduce new infections we've reduced deaths so we can make an impact and i think we'll New scientific innovations are likely to have a long-term impact, so I think those three points are what I see as the three key themes going forward, thank you and thank you all for listening and watching.

I'm sorry. I went overboard so it's interesting I hope you agree um so that's the end of the discussion for tonight I have to say we're going to continue this series through June because um I know people have been particularly interested in these questions and others so if you follow the

royal

society on the volcano website youtube channel etc you will see when we have the next discussion scheduled but for now I just have to say thanks everyone for listening thanks to the panel and good evening.