Developing enough COVID-19 vaccines for everyone

在世界各地,超过100 Covid疫苗项目ects - 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?

戈登,通常当你开发一个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.

克里斯,这是你'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