As the world continues to grapple with the debilitating human toll of the ongoing COVID-19 pandemic, experts such as Andrew Pollard , Director of the Oxford Vaccine Group and Chief Investigator on its COVID-19 trials, have been at the forefront of research, most significantly regarding vaccine development. The remarkable progress made by Professor Pollard and his team, captured by data published this week in the Lancet, holds out hope that an effective and safe vaccine might be available earlier than originally assumed, during 2021. He shared with Narayan Lakshman deep insights into the coronavirus endgame scenarios that might now be on the table.
There has been considerable excitement surrounding the data from vaccine development by OVG and AstraZeneca. Could you break the process down for us, explaining how the ChAdOx1 nCoV-19 vaccine works,what phase the trials are in, and what specific breakthroughs have been made?
The way the vaccine works is rather similar to most of the other vaccines in development. What we are trying to do is induce immune responses to spike protein. The spike protein is the protein that decorates the surface of the coronavirus and the virus uses it in order to enter into the cells in our body to cause infection. We are trying to make neutralising antibodies, which bind on to spike proteins and stop the virus being able to get into our cells and cause infection.
The new data published in the lancet this week shows that we can make those neutralising antibodies in our volunteers when we vaccinate them with this vaccine.
In addition to that, the vaccine also induces a type of white blood cell called T-cells, which are able to destroy our cells if they get infected by the virus. This might halt the infection. The combination of those two is exactly what we hope to induce with the vaccine and that is already quite an important milestone. We have not quite got there yet, because we now need to find out whether those immune responses are enough to protect people from infection.
Regarding what phase we are in, the data that has been published is from Phase 1, but we are now in the Phase 3 trials, with more than 10,000 people around the world getting vaccinated. This will try to answer the question about how much protection the vaccine could offer against the virus
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On the question of efficacy of the vaccine, is it possible that mutations of the virus might render the vaccine less effective than what was seen in the trials?
That is a really important question. We do not know the answer to that yet. So far, we do not see evidence that the spike protein itself has mutated so that the vaccine would not work. But that is something that has to be monitored, because these viruses, as they pass on from person to person, they do make mistakes in their genetic code. That could allow these mutations to arise and for new forms of spike protein to develop. One of the reasons why this may not have happened so far, as far as we can see, is that if they have big mutations in the spike protein, they would not be able to infect our cells anymore and it would be a dead end for the virus.
With the influenza virus, that is exactly what happens each year, and that is why we need to have a different flu vaccine used each year. It does also mean that if the coronavirus did this, we would have to use a similar strategy and keep changing the vaccine as we did for the flu.
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Is that a complex or time-consuming process?
I do not think that would be a terribly complex process to do. There would have to be a lot of work with regulators to work out how the process could happen at pace each year. It may actually be rather easier than for the flu vaccines, because of the way the manufacturing process works for the coronavirus.
How strong was the immune response that you observed in the vaccine trials, and is it something that would inspire hope?
That is the right question, but we do not know how strong an immune response is needed for protection. All we can say is that we are seeing immune responses that are better after a second dose. They are also not so bad after a first dose. We do not know if those are enough for protection, which is why we have to do these trials.
How much protection will the ChAdOx1 nCoV-19 vaccine offer? Will the effect be uniform across the population?
It is likely that there will be differences in immunity between people. A particular hurdle is for older adults, especially those over 70 years of age, where we know that their immune systems just do not crank up as much when they are vaccinated. So, it may be that it is more of a hurdle to get an immune response in that age group. We are actually studying that at the moment.
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There are at least 100 potential vaccines being developed across the world for COVID-19 – is it possible that they may differ in terms of impact on technology?
There are lots of different technologies being used, which is great, because that means that we have more chances of a vaccine being able to control the virus if one or more of those work. In the end, many of them are using the same approach, of making trying to make immune responses against the spike protein. The great news there is that if one of the vaccines that takes this approach works, it is likely we will have multiple hits on target. Worldwide, we will need a lot of vaccine, so having multiple developers successful is extremely good news.
When do you think the vaccine will be available for use, and how quickly do you think we would start seeing its impact at a population level?
It is an impossible question to answer because it is determined by how many cases occur amongst the population we have vaccinated. We can only tell whether we have got protection with the vaccine if we can prevent infection in our population of vaccine recipients and that is determined by how much transmission of the virus there is in the population that we are working in. I can tell you a lot about how much transmission there was last week, but I do not know how much transmission there is going to be next week. That is what we need to be studying about protection offered by the vaccine. If I knew the future, I could answer your question, but I do not.
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India is expected to have possibly the world’s largest number of COVID-19 cases by early 2021 – once the vaccine has been rolled out to scale, how long will it take to bring the pandemic to a halt?
The pandemic comes to a halt when there are enough people immune in the population, and the virus can no longer transmit from person to person. There are two ways we get immunity, the first is by getting the infection, and the other is through vaccination. For many diseases, we build up our immunity by getting the infection in childhood. That is true of many coronaviruses that exist in the world today. We have all had them as children, and that has built up our immunity. The difference here is that this is a new virus that no humans have seen before, and so it will take a while for that immunity to build up.
The problem is that if you just have a virus spreading wildly until everyone is immune, there will be lots of people dead in the meantime. That is where the vaccines may be able to intervene, by generating immunity without facing the consequences of the infection.
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To answer your question, we need to have enough doses of the vaccine available, and then we need to be able to vaccinate enough people to stop the virus in its tracks. But that is quite a big deal. First of all, you have got to manufacture it at an enormous scale, for a country like India, to be able to vaccinate a large proportion of the population. Then you actually have to get out and deliver the vaccine on a scale that has never been seen before. That is also a big hurdle. Even if you have a vaccine and you have enough doses, the logistics of preventing infection is everyone is going to be a huge, mass vaccination programme.
Many countries are thinking, initially, about how to protect those at greatest risk, like hospital workers, older individuals, and those with comorbidities. That is probably the right way to start.
Is there more that governments can and must do in terms of public health, infrastructure, and policy design for rolling out a vaccine, beyond looking at the right targets?
It is really important in every country that there are public health organisations looking at this question very carefully: if we did have a vaccine, how should it be used in our country, and how best should we deliver it? This is an urgent question for all countries. It does feel to me, that if we have a vaccine, it does get us out of this mess much earlier than if we did not.
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From your perspective, given the science that has gone into vaccine development, what would a reasonable price for the vaccine be?
I do not know what the price range would be. I did hear Adar Poonawalla of the Serum Institute of India speaking about some suggested prices but the important thing for most people in the world is that governments are likely to pay for this or have funding externally from international organisations to help them. So, hopefully for individuals being vaccinated, this will be of no cost to them, or a very low cost.
The partnership that Oxford University has made with AstraZeneca is a not-for-profit partnership. We try to make sure that we are able to ensure equitable access around the world. There is a facility that will help fund vaccines, particularly for developing countries, and to make sure there is equitable access.
