COVID-19: How to Vaccinate a Planet
This week, the search for a vaccine for COVID-19: will we succeed, and when? Plus, in the news, the search for a chemical fingerprint for severe COVID-19, bacteria that live inside cancers, and could something in your genes make coronavirus harder to deal with...
In this episode
00:54 - Finding phenomic fingerprints of COVID-19
Finding phenomic fingerprints of COVID-19
Jeremy Nicholson, Murdoch University
One of the biggest challenges posed by the pandemic is telling who is most at risk. Eighty percent of people will have very few symptoms, and maybe half of those may even have no symptoms at all. But one person in five will develop more severe - and in some cases life-threatening - disease. Now, a project set up between the University of Cambridge and another university, literally on the opposite side of the Earth, may have a solution: a chemical fingerprint present in the bloodstream that predicts whether someone is destined to get a very mild form, or a more severe form of the disease. And this matters, because knowing in advance who is likely to have trouble with Covid means doctors can intervene earlier with drug... and other therapies, potentially preventing severe deterioration. Chris Smith spoke to Jeremy Nicholson, From Murdoch University in Perth, Western Australia…
Jeremy - The challenge that we've set ourselves, is to use a range of advanced technology platforms for very rapidly profiling the chemistry of blood, and possibly urine samples, from COVID patients to try and predict how severe their disease will become. So at the moment, we have a number of different ways of testing for the presence of the virus, and potentially how you immunologically react to the virus. But what we can't say in the early stages is are you going to need to be on critical care or not? And if we could detect a signature for that, then we'd be able to manage those patients much more efficiently.
Chris - What might that signature look like Jeremy? And how do you go about finding it?
Jeremy - We use a range of advanced technologies you normally find in a chemistry laboratory, they measure hundreds or thousands of different molecules that are in your blood or in your urine. So the first real question is: can we find out whether or not, using this range of different chemical technologies, that COVID patients are different to everybody else? And what I can tell you is that our initial tests show that that probably is the case, but what really we want to know is whether or not that signature predicts the severity going forward. For that, what we need is longitudinal sampling. So we have a series of different samples taken from a bunch of patients, and we follow them through and we build a model of how their chemistry is changing with time. At the end of the patient journey, we will know who is severe. And what we're going to do is look at the earlier stages of the chemistry to see if there was something very specific associated with that turn towards severity.
Chris - So it's not just one molecule that changes, you're talking about a whole constellation of molecules, and how the levels of those different chemicals relate to each other. And there might be a particular spectrum, which is very specific to people who are going to get severe disease, compared with people who are not. And if that's present before they even get infected even, or very early in the course of the disease, you can say those are the people that we need to intervene early, or they're the ones to watch, we could reassure the rest.
Jeremy - Well, that's absolutely right. I mean, we measure probably as many as 20,000, 25,000 compounds using these different technologies. That's lots of different types of small molecules, but the signatures come down to a much smaller numbered subset of those. Maybe only 10 to 20 of those things will be really reporting information that's relevant, that's specific and sensitive for the disease and also, reporting on how the disease is likely to progress.
Chris - How are you going to find them in the first place though? Because this to me is, you're hunting for a small number of needles in a massive biochemical haystack. So how do you know what those needles are in the first place?
Jeremy - Well, the way that you make the predictive model, is that you have to have samples that you know are from people who, shall we say only, had the mild disease and others, which went on to get the severe disease. And then you do a statistical analysis to find out which of all the different combinations of metabolites in there are the ones that are most closely associated with the biological question, which in this case is the prediction of severity?
Chris - Where are the samples going to come from that you're going to analyse? Is this just Australia?
Jeremy - Potentially samples from several places in the world, but one of them, of course, is your own institution, Cambridge university., Where Cambridge, I think the Addenbrooke's hospital has handled more samples than have probably gone through the whole of Australia. So there is some very well designed studies there on COVID positive patients at different stages of the patient journey, and with different degrees of severity. And we are in the process of having an arrangement to ship some of those samples over and do a comprehensive analysis.
Chris - And just lastly, some groups have stood out as being potentially more vulnerable than others. I'm thinking older people, people with male sex, also people from certain ethnic backgrounds. We don't know though, to what extent socioeconomic factors is playing a role. So is this going to help us to disentangle that aspect as well?
Jeremy - Well, all of that background information would be important metadata that we would co-analyse. And of course there are lots of different reasons why all of those things could contribute to your risk for, not just for COVID-19, but for lots of other diseases as well. The important thing is though, you're measuring the contribution from genes, and environment, and diet, and all your lifestyle into your individual metabolic signature. So when we run our various fancy machines, we are picking up the signature of your life. And the signature of your life also, is very closely related to your disease risks for anything. And that includes severity of disease. So the nature of the science that we do, unraveling the gene environment interactions that creates the metabolic phenotype, which is related to the risk, by definition, it will be related to those other risk factors, as well as age and gender and ethnicity
07:34 - COVID-19 treatments called into question
COVID-19 treatments called into question
Anthony Davenport, University of Cambridge
There was optimism when UK Health Secretary Matt Hancock announced that a drug called remdesivir, which appears to shorten recovery time by about four days for people with Covid 19, is being made available on the NHS. The Health Secretary said it was probably the biggest step forward in the treatment of seriously ill patients since the crisis began. On the other hand it turns out a drug being touted, and taken, by President Trump isn’t reliably good after all. The effect of hydroxychloroquine has been called into question after an analysis by American researchers who say it might even make things worse. While their study has limitations - particularly the fact that they looked at the drugs’ effects at very high dose - the World Health Organisation has suspended trials of hydroxychloroquine, along with those of another chemically similar drug called chloroquine. The research has been published in the Lancet medical journal, and Phil Sansom has been discussing the drugs with Cambridge University pharmacologist, Anthony Davenport...
Anthony - Both of them are antimalarial agents and it was originally thought that they might have some benefit in patients with COVID-19.
Phil - Why, how do they work?
Anthony - I think the way they work is unclear, although it is thought that because the virus is taken into very specific organelles within the cell, which are acid, these two drugs are thought to change the pH or acidity, to make them more alkaline. So they're less likely to gain entry.
Phil - Tell me about this Lancet study. How did they investigate this?
Anthony - So it's important that people who are actually on many of these drugs continue to do so. And if they've got any concerns, they should talk to their doctor. But what this group did was to look up the patients records from over 600 hospitals around the world, and they really looked at four different groups. These were the two drugs on their own, or the two drugs in combination with antibiotics.
Phil - So these are people who got coronavirus, were already taking hydroxychloroquine and chloroquine?
Anthony - Yeah. So what they asked was: the patient had to have evidence that they had the virus, and they used as their control from these four groups, about 80,000 individuals who were on other treatments. And they also excluded patients who were on ventilators. So in other words, they were looking at people who had an early diagnosis and were not particularly sick.
Phil - And what did they find?
Anthony - Patients who are taking one of those four drug treatments actually had a significant increase in deaths in hospital compared to the control group.
Phil - Do we know then whether hydroxychloroquine and chloroquine are dangerous, if you've got COVID-19?
Anthony - We can't conclude that. But what it says, there doesn't seem to be really any evidence of benefit. One of the limitations of this study was that obviously, they didn't set out to carry out out a clinical trial, where you would have different concentrations of the medicines that you were testing. In this case, it looks as though the concentrations of some of the medicines may have been too high. So it's important to bear that in mind. But what it does suggest is that there should be some more testing of these compounds, to make sure that they are safe at the concentrations that they're being used.
Phil - What should I make of this? Is this, sort of, showing the limitations of a drug that hasn't been tested yet?
Anthony - Yes. I think it's very important that, as I emphasised, the drugs are normally used for very specific diseases and they've been shown to be safe and effective. This is a completely new clinical indication. We don't really understand the mechanism of how the virus does so much damage.
Phil - Now there's been news here in the UK about another drug called remdesivir, what is it?
Anthony - It's basically a nonspecific antiviral agent. In other words, it tries to stop the virus reproducing. It mimics some of the residues, which are in the virus, and it prevents the virus from replicating. What they've allowed is that clinicians are able to prescribe the drug, but there is no evidence yet that this drug is an efficacious drug in the setting of patients with COVID-19. A large clinical trial in the United States has suggested that there was a reduction in time to recovery, but we don't yet know whether or not there's going to be any longer term benefit.
Phil - What kind of benefit are we talking? Is it fully treat, help a little bit?
Anthony - I think if we think about other viruses, such as HIV-AIDS, generally, it's a cocktail of drugs. So you may wish to combine it with other drugs, which reduce the severity of the symptoms, but it's unlikely on its own to be a game changer. It's not going to be a magic bullet.
13:42 - Gene variant linked to greater COVID-19 risk
Gene variant linked to greater COVID-19 risk
David Melzer, University of Exeter
The UK Biobank isn’t the place to go and get cash from. As the name suggests it’s a bank for biology. It contains samples and health information from around five hundred thousand volunteers and gives anonymous data and samples to researchers here and from overseas. The aim is to help them come up with treatments for a wide range of serious and life-threatening illnesses including cancer, heart diseases, stroke, diabetes, and so on. As you can probably tell Biobank’s data, gathered over a number of years, is potentially also very useful in the fight against Covid 19, and this week a study from the University of Exeter found that those with a certain genetic make-up... may have a worse time dealing with the disease. A gene which usually helps the body transport fats, called APOE, has emerged as a risk factor for the disease: if a person carries what’s referred to as the APO-E4 forms of the gene, they’re more than twice as likely to succumb to Covid-19. What’s interesting is that this genetic profile is also linked to developing dementia. And initially when the team looked at who was getting Covid, dementia sufferers were heavily represented. But when this was taken into account, there was still a strong link: there were people with Covid and APOE4 who didn’t have dementia. This means that it’s not the dementia itself, but something about the APOE gene that’s changing people’s risks. Adam Murphy’s been hearing from David Melzer how he spotted the link...
David - The disease that came out amongst the oldest sample as by far the biggest risk factor was dementia. People who had been diagnosed with dementia since baseline approximately 12 years ago were three times more likely to be admitted to hospital and test positive for COVID. And so the obvious thought was, "could this possibly be an effect of the APOE gene?" The APOE4 mutation has also been linked to a series of viral infections, including HIV. So it was the obvious question. The other possibility of course is the higher risk of dementia might be due to higher prevalence of dementia in care homes. So it seemed an important thing to explore. It turned out that people with a full 4 mutation were over twice as likely to test positive in hospital during that peak period. And we did a number of tests to check whether it was robust, for example. It was remarkably robust, really; the estimate didn't change at all. So we thought it important to publish so that other groups could look at it and check it in their own data.
Adam - How can you tell that the risk is based on the gene? How do you factor out things like age and that kind of thing?
David - We have 12 years of hospital records on the whole sample of over 300,000 people. The UK Biobank study has also linked up these diagnostic data to primary care records, so we can search their anonymised primary care records. Basically we identified the people who've been diagnosed before and exclude them from the analysis. And as I said, it basically made no difference. So it doesn't look as if the association between APOE, the risk gene, and COVID-19 positivity in hospital is due to dementia. People in Biobank with this mutation - double mutation - actually had dementia.
Adam - Are there any recommendations that come off the back of this?
David - Well, one of the things I've been concerned about is in the early phases of the pandemic, many countries introduced age-based cutoffs for risk. In the UK age, 70 was used as an indicator. And a lot of my group's work over the last 15 years has been how different individual older people are. I mean, some people die of age-related diseases in their sixties; others go on to be centenarians and remain active even beyond the centenarian age. So lumping everybody together on the basis of chronological age is convenient - I mean, I can see why you would do it at the height of the pandemic - but we were hoping to inform policies going forward to be more focused on what the actual risks are.
The bacteria in cancer
Ravid Straussman, Weizmann Institute
Back in 2017, Chris Smith spoke with Israeli scientist Ravid Straussman. Looking at pancreatic cancer samples, he'd stumbled on the surprising observation that the majority of the cancerous cells he looked at had bacteria lurking inside them. These microbes appeared to be helping the cancer cells to survive and even defending them from chemotherapy drugs. Knocking out these bacteria might therefore be an additional way to target cancer cells, or at least sensitise them to some anti-cancer drugs. But is it just pancreatic cancer that does this? In a new study from the Weizmann Institute in Israel, published in Science, by widening the search, it looks like the answer is no, as Chris has been finding out...
Ravid - A few years ago, we found almost incidentally that inside human pancreatic cancer - so inside these tumours - one can find bacteria. We're also able to show that these bacteria can protect cancer cells from chemotherapy, we found that these bacteria can inactivate the chemotherapy. So our challenge here was, we wanted to know if this is a more general thing. Can we find bacteria in many different tumour types? So what we did was we took biopsies or tumours from 1500 cancer patients. These included breast cancer, bone cancer, pancreatic cancer, brain cancer, ovarian cancer, lung cancer, skin cancers. And we were surprised to see that in each one of these cancer types, we could find bacteria. We found that in every cancer type there seems to be different bacteria. So you kind of find the same bacteria in different patients, let's say with breast cancer; but the bacteria that are present in patients with breast cancer are very different from the one that you find in lung cancer or other cancer types.
Chris - Do you think these bacteria are viable? It's not just that the tumour cells are being like a giant sieve and the bacteria that naturally go around the bloodstream anyway, they're getting grabbed in a deactivated or dead state and just pulled into these cancer cells, 'cause they're abnormal cells. Are these live, viable bacteria?
Ravid - For sure these bacteria are viable. We were able to grow live bacteria from these tumours.
Chris - What comes first then? Does the tumour develop and then it recruits these bacteria from somewhere, or do you think the bacteria settle in tissue that's destined to become a cancer and the two co-evolve?
Ravid - We don't have good enough data to answer that for all these cancer types. My bet is that both of them can be true. It's been known for many years that some viruses, as well as some bacteria, can contribute to the transformation process - meaning transforming normal cells to cancer cells. But it can be the case, as you mentioned, that you have some tumours; and after you have these tumours, bacteria find refuge in them. So we're not sure yet which comes for us in the process of tumourigenesis.
Chris - It's not just a random process though, is it? Because you're seeing these very similar types of bacteria that crop up time and again in the same sorts of tumours, and they're quite different from other sorts of tumours; which suggests there's some kind of control going on, something is determining whether that's coming from the bacteria selecting their host tumour or the tumour selecting their bacteria they want to give a home to. Something is guiding that process.
Ravid - Absolutely. A nice glimpse that we had into this process is probably coming from lung cancer. We looked at lung tumours from smokers and patients that never smoked before. And when we compared the bacteria inside tumours coming from the lungs of smokers and nonsmokers, we saw some bacteria that are very specific only to the smokers. And then we looked into the genes that are found inside these bacteria. What we found is enrichment of genes that can degrade chemicals that are found in cigarette smoke; for example, nicotine or other chemicals. So what we reason is that patients who smoke have all these smoke-related chemicals in their lungs. And bacteria that can chew up on these chemicals are probably being selected to live in these types of tumours.
Chris - What are the implications of this finding then? Do you think that this offers us an avenue to management or therapy? Because is it possible to do something to the bacteria and exploit their presence there to destroy the cancer?
Ravid - I think this is the most exciting thing. The fact that you have bacteria in tumours probably implies that they have a lot of crosstalk with the tumour cells, with the immune cells, and they're probably affecting much of the tumor biology that we see. A good example for it is we found, for example, that tumours of the skin... we looked at patients that responded or did not respond to immunotherapy. And we found that there are specific bacteria that are more prevalent in the responders or the non-responders, suggesting that maybe the bacteria also affect the response of these patients to immunotherapy. And if we learn more about how to modulate the bacteria in the tumours we might find completely novel ways to treat cancer patients.
24:29 - How would a COVID-19 vaccine work?
How would a COVID-19 vaccine work?
Gordon Dougan, University of Cambridge
Dozens of labs around the world are all working hard to make a vaccine for COVID-19. But what would that vaccine look like, and how does it work? Chris Smith spoke to University of Cambridge vaccinologist Gordon Dougan about the science behind the vaccine...
Gordon - When we, as children, we see lots of diseases, for example mumps and chickenpox. And we also know that those diseases usually only occur once; so we get protected, or immune, to those diseases. And what a vaccine does, it takes the germ or the bacteria or the virus that causes that disease, and we make an inactivated form of that germ which is safe, does not cause a disease, but mimics the disease. The body gets fooled into thinking that it's been infected; it sees the bacteria, the virus, the germ, and induces protection against the disease so we become immune.
Chris - How long does it normally take to make a vaccine then? Say I discover a disease, or we've got a disease in the population and we decide, "this is a big problem, we're going to fund a vaccine, we're going to make a vaccine." How long would that journey normally take then?
Gordon - Well the reality is it can take a long time. The average time from discovery to making a vaccine can be up to 10 years or even longer. And as you start to make the vaccine, it becomes more and more expensive as you try to develop the vaccine, and that puts a lot of people off trying to make vaccines. But, there are different stages to making the vaccine, so we could consider trying to shortcut the time that it takes. But the real important thing with a vaccine is it has to be safe.
Chris - And how do you prove that it is?
Gordon - You have to be very careful, in the sense that you have to use your own sense and scientific knowledge to create a vaccine which will not cause any side effects. You then take it through what we call the preclinical stage, which means we test in every different way we can possibly do to see whether it would a) induce protection, but b) also that it wouldn't cause side effects. And then we take it eventually into studies in humans: first of all in very small numbers of humans, but then gradually ramp up to try to see if we can vaccinate larger and larger numbers of people in a safe manner.
Chris - So what challenges are we facing trying to make a new vaccine against this new disease, this new coronavirus, that's the cause of COVID in some people?
Gordon - I think the main challenge is that we've never made a vaccine against a coronavirus before. We've tried to make vaccines against coronaviruses in animals but we haven't got any of them to work so far. But we do have a lot of knowledge about how to make vaccines against viruses, and lots of different tricks if you like to try to make them. And so what we are doing now is we'll be taking each of those approaches and trying them out systematically to see if we can get one vaccine that will induce protection.
Chris - And what's actually being pursued at the moment? Who's working on this and in what sorts of numbers?
Gordon - It's incredible really in that there's probably at least a hundred different groups of people around the world trying to make a vaccine. And they're taking a number of approaches, but there's about four different types of approaches. There's what we call a live attenuated vaccine. If you remember the polio vaccine you get as a child on a sugar lump, it's what we call the modified form of the disease-causing agent, the germ, which can be seen by the body as the causative disease agent; but it doesn't cause disease. The second way you can do it is you can actually inactivate that germ, that bacteria or virus, or take a small portion of that bacteria or virus; and that mimics the infection a different way. The last two approaches are slightly more complicated. One is what we call a vectored vaccine, and that's the approach being taken by the Oxford group which has gained so much publicity. And there you take the protective part of the virus, put it into another virus that might infect chimpanzees or other animals, but not humans; that delivers the vaccine into the human and induces protection. And the last form is a very novel form which is actually a genetic vaccine, the DNA- or RNA-based vaccine: in that you inject the DNA or RNA and you allow your own body to make parts of the virus that can protect you and induce immunity.
Chris - So when you say you inject bits of DNA or its chemical relative RNA, are you saying you take the genetic message for the, say, outer coat of the virus; and you put that genetic message into the body, and our own cells pick that up and decode it, and then show that to the immune system as though you'd injected the virus for real?
Gordon - That's exactly what you're doing. You try to package it in a little package that looks like a virus or a bacteria, you inject it, and the body is fooled. It basically starts making parts of the virus in the way would make normal proteins and other parts of the cells of your body during normal life. So you're really fooling your body with a genetic tool, if you like; a gene tool.
30:55 - Developing enough COVID-19 vaccines for everyone
Developing enough COVID-19 vaccines for everyone
Charlie Weller, The Wellcome Trust
Around the world, more than 100 Covid vaccine projects - exploring more than 10 different types of vaccine - are underway, 7 of them in clinical trials already. About half are in the US and about 70% of them are commercial ventures. Some have questioned why so many projects are all running side by side, potentially duplicating work. But this is actually a good idea: pharmaceutical companies usually expect their experimental drugs to take 10 years to develop and to fail 90% of the time. So having a lot of independent vaccines under development improves our odds of winning. Longer term, it’s proposed to push forward with the 5 most promising candidates and then select from those the two best contenders. But to minimise subsequent delays, and make vaccines at the sorts of scales we need - and within the required timeframes, inevitably means that we’re going to have to take some risks. Adam Murphy spoke about this with Charlie Weller, Head of the Vaccines Priority Area, from the Wellcome Trust, one of the charitable funders supporting Covid research, and then Chris Smith spoke with University of Cambridge vaccinologist, Gordon Dougan...
Charlie - Covid has really made us think very differently about how we approach these clinical trials and many of the clinical trials now are being done in parallel to really accelerate that process. If everything goes to plan, we might have some of that data coming out at the end of this year. But even at that point, this is looking at whether the vaccine protects thousands of people, maybe in one or two countries. And that's not the same as having a vaccine for all age groups, all people, all countries. So we need a vaccine on a scale that we haven't had to develop before. So at the end of this year is really where we know whether we've got an effective and safe vaccine. And that's still a big if.
Adam - Let's say that it does come good, what are the challenges in turning a vaccine into enough vaccine for everyone?
Charlie - The challenges that Covid has really brought to vaccine development is the speed at which we want a vaccine condensing that 10 years down into 12 to 18 months. And the scale, how many doses, how many people we want to vaccinate. The challenges are really centred around those two. Once we have that data that shows that we are likely to have a safe and effective vaccine, if we started scaling up manufacturing at that point, it's going to take a long time. So actually at the moment we are globally looking at scaling up manufacturing now, at financial risk, before we know that the vaccines are safe and effective. Which means that it's likely that some of the manufacturing facilities that will be scaled up will be for the candidates ultimately to fail. And that is a huge financial risk, but if we want to be quick, and if we want to work at the scale we need, then that is a financial risk the global community has to take.
Adam - Does that mean, then that say the same factory that could be used to make, say an attenuated vaccine that can also be used to make a DNA one or all the other different kinds are they interchangeable?
Charlie - At the moment, there are over a hundred different vaccine candidates which are in development. And that is fantastic because what we have is a variety of different approaches, which really gives us the best chance of getting a safe and effective vaccine. But if we're trying to now set up manufacturing facilities for all these different types of vaccines, they're not interchangeable. The processes are quite different. It's not just a case of building lots of manufacturing facilities everywhere. We don't yet know which type of vaccine candidate will be the effective one.
Adam - From a, I suppose, from an immunology vaccine science standpoint, is there anything different you have to think about when you're mass producing vaccines than when you're just doing the initial research to get one?
Charlie - There is a whole science behind scaling up manufacturing. What you might produce in hundreds of doses is very different to how you produce billions of doses. And there are many potential pitfalls along scaling up as well. For example, we know with some of the more traditional vaccines, like the inactivated vaccines, these processes have been tried and tested to be scaled up for many different diseases. We don't have that for some of the new and innovative vaccines: the nucleic acid vaccines, the viral vector vaccines, we don't know how to scale up. So there are a lot of unknowns.
Adam - Do you have any idea of what a timeline we might be looking at is from 'human trials are over' to 'there is enough made'?
Charlie - If all goes well, it's likely that we'll have some data, some information about whether those vaccines are safe and effective towards the end of this year. So I do think that next year is a feasible timeline to be aiming for, to have some doses, limited by which approach is successful.
Adam - Charlie Weller there from The Wellcome trust.
Chris - Now with us is Cambridge vaccinologist Gordon Dougan. He was listening to that. So Gordon, Charlie just talked about, one of the things she said was a trial of a few thousand people in one country being relevant to people of all ages and all countries. What was she getting at when she said that?
Gordon - Well, normally when you're developing a vaccine, you have to prove that the vaccine protects and we call this the efficacy of the vaccine. So you have to find a location where the disease is relatively common, and you have to bring in enough people really to be able to measure protection. So you often would have to go into a location with quite a high incidence of disease. And then you might say, well, I want to vaccinate children, if it's a children's vaccine, or you may want to try to immunise the whole population, then you would obviously take people of all age groups. You would normally start with healthy individuals and then move down into children. You would never start a vaccine trial, for example, in children,
Chris - We've been getting quite a lot of mixed messages around children and immunity and immunity to coronaviruses in general, though, throughout this outbreak, haven't we? Where do we stand on this? Do we think that when we go in with a vaccine, we're probably going to get immunity to coronavirus? And is that immunity going to have a reasonable lifetime, do you think?
Gordon - Well, the answer to be brutal is we don't know yet. We're hoping that we will get immunity and I'm optimistic about it simply because for most diseases that we've tried to make a vaccine eventually we've been able to do it
Chris - Well in HIV, we haven't succeeded have we. I mean, a hundred million people, and 40 years later, we still don't have an HIV vaccine. It will be the 40th anniversary of its discovery soon.
Gordon - Yes, but HIV is a very variable vaccine, whereas the coronavirus is much more invariable and that helps.
Chris - What do you mean as in how, how fast it's changing? You mean it's mutations? How fast it adds changes to its genetic material? Is that what you mean?
Gordon - Exactly. So what we say is the HIV virus is antigenically diverse and that means it's all sorts of different forms of the virus. Whereas coronavirus we already know is very limited in its variability. And if you're going to target the coronavirus, you've got a better chance of protecting compared to HIV, for example.
Chris - I want to read you a quote from Melinda Gates because this is something which I think plays very much to your strengths and where you're coming from, because she said, right at the outset of all of this, "if there is covid anywhere there is covid everywhere. And if vaccinations are not distributed, everywhere, relapses can occur everywhere". And what I think she's getting at is that basically if we sweep the dirt out of our own backyard, into the street, the wind will blow it straight back in here, unless we help everyone to clear the street up and their own gardens too. This is a global problem. It needs a global solution.
Gordon - Yeah. I mean, what she's really talking about are reservoirs, you know, where the disease can hide away. And they often hide away in the most impoverished or the poorer parts of the world. And they're the people that are most difficult to vaccinate because first of all, they cannot afford to buy the vaccine. And also tougher to go that last mile, we say, where we can actually reach them, particularly in areas, for example, where there's social disruption or wars going on, it's incredibly difficult to run a vaccine program.
Chris - The reason I put that to you is because obviously you have a track record for working in poorer countries and successfully deploying vaccines into those places. Are they likely to be able to afford the likes of the sorts of vaccine and the sorts of infrastructure that would be needed to give people doses of what the University of Oxford's team are currently testing?
Gordon - To make what we call an affordable vaccine, you have to start from ground zero, right from the very first point of designing and manufacturing, right through to delivering the vaccine. You have to think about ways of saving costs. And what we aim for really is what we call 'a dollar a dose vaccine' whereby it can be deployed at very low cost. So there's two challenges. One is the affordability, but also as soon as you get into those areas, you lose what we call the cold chain, because most medicines require refrigeration to be safe. And right like when you get a delivery of food from the supermarket, you put it into a fridge to preserve it. And what we had to design is vaccines that can endure being outside of the cold chain for a period of time, we call them stabilised vaccines. So we need a combination. We'd have to think the whole process through to make that affordable stabilised vaccine.
Chris - And is that what you're doing?
Gordon - Yeah. So we've set up in conjunction with the Wellcome an operation company in India, and there's been other places. There's a centre called the international vaccine institute in Korea, which was set up around 15 years ago to try to create vaccines that could reach the most needy, and they're being relatively successful. We've just had a vaccine, for example, against cholera that we started around five years ago, which is now being delivered to a company in India, ready for delivery into the population at a dollar a dose.
Chris - So you reckon that you'll be able to do this, but obviously you're going to do this at a slower rate than the Oxford team, because presumably you're just getting started on this now.
Gordon - Yeah. And it's not quite the same tension and rush in the sense that the Oxford team have to deliver to an incredible timetable under pressure. And of course they can't take all the considerations into account achievement, the vaccine that I've mentioned. And so what will happen in our point, we will try to do that
41:35 - Vaccinating the world fairly
Vaccinating the world fairly
Orin Levine, Bill and Melinda Gates Foundation
Critical to the success of any COVID-19 vaccine programme is going to be forward planning: thinking ahead to a time when we have a safe and effective vaccine that we now need to take to the world population. We need to be making decisions about who and where we’re going to vaccinate, and making sure that the capacity and infrastructure is ready on the ground so there are no delays in the roll-out. Adam Murphy spoke with Orin Levine, director of the global delivery programs at the Bill and Melinda Gates Foundation, which has already committed more that 300 million dollars to the fight to find a COVID vaccine, and then Chris Smith spoke briefly to University of Cambridge vaccine expert Gordon Dougan, about the challenges that lie ahead...
Orin - I have two things that keep me up at night. One is that we don't discover a vaccine in spite of all the effort that we do. And then the second, which is really the part that I'm focused on, is when we get it, how do we get it out there to everybody who needs it as quickly as possible? And success at that is going to require quite a lot of cooperation. It's already requiring the vaccine manufacturers to collaborate and cooperate in ways that we haven't seen before. And that's starting to happen. When that successful collaboration produces a vaccine, then we have to figure out how are we going to allocate the doses that we have, and how are we going to make sure that we've got everything lined up so that the day that the vaccine arrives in a country, is rolling out and getting into people and starts the process of protecting people as quickly as possible. That's going to require a lot. It's going to require communities to have a dialogue about when the vaccine arrives, what's the sequence by which they want to roll those vaccines out. I think there's probably widespread agreement that our healthcare workers are essentially heroes of our time that they go in every day to treat people and take personal risk and to be able to sustain our health in spite of risks that they may be taking to themselves and their own family. And they're probably going to be at the front of the line, but after we vaccinate healthcare workers, where do we go next? Are we going to try to interrupt transmission in hot zones? Are we going to try to put our economies back to work by getting the workforce vaccinated? Are we going to allocate to our most vulnerable people? Because they will suffer the most when an infection comes? These are all the kinds of questions that need to be answered by countries and communities as we get a vaccine and start to roll it out.
Adam - And so that's like the medicine of the vaccine, but how are we globally doing in terms of the infrastructure we need to do that. Like getting places where people can go, and even things like syringes for people, do we have enough of those kinds of things?
Orin - So these are great points, and these are exactly the kinds of things that people are starting to ask questions about and prepare for is, Holy cow, if our dream comes true and it all arrives, are we going to have everything that we need? There are a couple of really, really strong foundations of success that we have to build off of. First of all, the global immunisation program is a strength of global public health. We have experience in setting up campaign-style immunisation. It takes different forms in the UK and the US and places like that, every fall/winter, we essentially prepare for the flu epidemic that's coming and campaign to get people vaccinated against seasonal influenza. In a lot of the parts of the developing world where outbreaks of measles and yellow fever and meningitis still occur, we have a lot of capacity in trying to establish with communities points where people go and get vaccinated on mass, to be able to prevent that. In order to do that, though, we've got to have supplies, the kinds of things that you asked about like syringes, and there's a strong, robust supply system for syringes, but we need to tell them in advance, we're going to need more than we were using next year. The most important part though, is going to be making sure that health workers feel comfortable, feel safe, feel protected, going to deliver services. And that communities trust that the healthcare workers that they're being served by are going to be safe and protect them, and that the vaccine that they're getting has been rigorously evaluated and is the right vaccine for them. And so we're not only working the supplies of syringes and healthcare workers. We've also got to work, to prepare communities, to be ready to receive the vaccine. And that is a big, big piece of work for us and needs to start urgently.
Adam - Even everything going smoothly, vaccinating an entire planet of people is still like a Herculean task. So what kind of timeline do you think we could be looking at to get people vaccinated?
Orin - Well, it's hard to know exactly when we'll get the first vaccine, because there's so much science that's going on right now. And there's so much uncertainty each day that we do a little bit more science, we learn a little bit more. My suspicion is that the best case scenario is early 2021, that we're looking for a vaccine being licensed and available. But one of the things we've learned is it's really important to start planning immediately. And so we're going to start planning for success today, begin that dialogue around what will it take when a vaccine arrives to make sure that it's equitably distributed, safely delivered, and delivered at scale to everybody who needs it.
Adam - And then just lastly, if there was anything you wanted people listening to take away from this kind of work and the work you're doing with the Gates foundation here, what would it be? What would you want them to know?
Orin - I guess I'd want them to know probably two things. One is in my experience, I've never seen such a collaborative, coordinated, global effort to try and help humanity out of a jam. The intentions of a huge universe, a huge enterprise of people right now dedicated to trying to discover and make a vaccine safe, efficacious, and available is really a heroic undertaking. And trust them, they're about it for the right reasons and really going above and beyond to try and help the world right now.
Chris - Hear hear, couldn't put it better myself, Orin Levine there. And one of those experts who is trying to develop a vaccine and help the world, he's with us at the moment, that's Cambridge based, vaccinologist Gordon Dougan. Gordon in the program this week, we've highlighted a number the constraints and the hurdles that we need to overcome to try to achieve an effective Covid vaccine. But what in your view do we absolutely need to make sure we prioritise to make sure this happens and make sure we don't drop the ball?
Gordon - I think that the biggest challenge, and Orin hinted at it, is that we need to be able to measure the protection, the ability of the vaccine to protect. It's a bit of a race against time. As we drop down the level of virus in the community, the chances of getting a measure of protection are diminished. So that's one of the biggest hurdles and challenges that we have to face. Can we prove the vaccine is protective?
49:30 - QotW: Has life on the ISS been affected by coronavirus?
QotW: Has life on the ISS been affected by coronavirus?
Phil Sansom has been looking up at the International Space Station thanks to this question from listener Fady…
Fady - Has life changed for astronauts on the ISS due to coronavirus, and are astronauts still allowed to be sent to and from the ISS?
Filippo - Astronauts’ lifestyles on the International Space Station have not significantly changed during the coronavirus pandemic. No astronaut physical distancing or donning of personal protective equipment are enforced on board.
Phil - That is Filippo Castrucci, a flight surgeon at the European Space Agency - one of the main organisations involved with the International Space Station.
Filippo - Also, to date, the pandemic has not affected crew changes on ISS. In fact, since the infection started spreading around the world one crew has launched to ISS and two have returned to earth. The next launch is expected as early as this week.
Phil - So why is it business as usual? It’s not that the coronavirus isn’t a huge issue - it’s just that any bug in the astronauts is a big problem, so they’re always on high alert.
Filippo - Crew and crew support personnel are always properly immunised and undergo two weeks of pre-flight quarantine at the launch site. With COVID-19, the quarantine has extended to one month and there is now dedicated and repeated testing.
Phil - As far as anyone knows, that’s more than enough time to let the virus burn itself out.
Filippo - And in the unlikely event that a severe transmissible disease as COVID-19 should be suspected on ISS, given that the astronauts share living spaces, hygiene facilities and air, by the time the first individual shows early symptoms, it is likely that the entire crew is already infected. As the consequences for crew health and mission safety may be severe, and the known severity of COVID-19 exceeds the in-flight treatment capabilities, evacuation back to Earth is the most appropriate measure.
Phil - Meanwhile, other space programs are going ahead too - evan_au mentioned on our forum the Perseverance Mars rover, which if it misses its July launch date, won’t get the right planetary alignment again for 18 months. So NASA have appropriately decided to persevere. Thanks to Filippo for answering that one. Next week’s question comes courtesy of listener Denise:
Denise - There are plants that contain saponins, and were used by Australian aboriginal people as bush medicine. Aboriginal family members in remote areas are concerned about the coronavirus, but do not have access to hand sanitisers, or even soap. Is there any research on the antiviral properties of saponins?