We ultimately should be able to make a pan-coronavirus vaccine, says theoretical epidemiologist

by Annette Ekin

The world’s pressing need is a vaccine to fight the current threat of Covid-19, but ultimately we may be able to develop a pan-coronavirus vaccine, Sunetra Gupta, a professor of theoretical epidemiology at the University of Oxford, UK, said at the European Commission’s annual research event.

Prof. Gupta was speaking on a digital panel at the European Research and Innovation Days on 22 September along with other scientists to discuss how they’re steering their frontier research areas to address challenges brought on by the pandemic.

Prof. Gupta said her work for the past 25-30 years focusing on a theory of how pathogens evolve, in particular those that exist in multiple strains such as influenza, put her team in a good place to study the coronavirus.

Her group has developed models to better understand coronavirus from the limited data available, from how deadly it is – work which drew attention in the UK in March for suggesting lower infection fatality rates – to determining the threshold of herd immunity. They’re looking at how many people are likely to be immune and at what rates of seropositivity – where antibodies show up in the blood of people exposed to coronavirus – can reveal.

Her team is developing lab tests to look for coronavirus antibodies to study how many people have been exposed to the virus and also whether other coronaviruses confer protection against it.

Prof. Gupta’s work on the evolution of influenza antigens – substances that provoke an immune system response – has been key to her coronavirus work. Her team came up with a new way of making a vaccine that covers a diversity of strains by identifying influenza epitopes, the part of antigens that attach to molecules, with limited variability.

‘It’s like saying influenza may have lots of hats, but it only has four shirts,’ she said. Their technology has been licensed to develop a universal flu vaccine.

To use this analogy, coronaviruses have a more limited wardrobe.

‘Each coronavirus kind of sticks to its own wardrobe,’ said Prof. Gupta. ‘It doesn’t have the luxury, like flu, of saying: “Okay, tomorrow I’m going to wear the red shirt.” It just can’t do that. So that’s quite useful (for) making a vaccine.

‘This is why I feel – have confidence – that we will be able to produce a vaccine towards this virus because it’s not going to suddenly turn around and change and be antigenically very different. So at that level, it’s much more like measles than flu.’

Immunity

Unlike measles, lifelong immunity is unlikely. ‘With coronaviruses you tend to lose immunity and get re-infected every three or four years,’ Prof. Gupta said.

When it comes to epitopes of limited variability, it’s likely that the four currently circulating coronaviruses have some ‘clothes’ in common, Prof. Gupta said. ‘Each coronavirus has its own wardrobe, but there are common bits that they share within their wardrobes.’

Prof. Gupta hopes the pipeline they’ve established can be used in the future to make a pan-coronavirus vaccine, she said. ‘That’s one thing that we are quite seriously pursuing.’

But, she suggests, vaccine research is likely to get harder in the future.

‘I always teach my students that the vaccines that we have are the low hanging fruit on the vaccine tree. They are where we’ve been able to mimic natural immunity,’ said Prof. Gupta. ‘And they’re also the ones that induce very strong natural immunity, and long-lasting natural immunity, like measles, mumps, rubella.’

Given coronavirus’ relatively short immune response, she says that we want a vaccine that gives enough immunity to stop people from dying and helps the immune system keep them alive in case of reinfection. ‘So I think that’s the goal.’

Global challenges

The annual research event held on 22-24 September brings together scientists, policymakers, entrepreneurs and members of the public and is based out of Brussels, Belgium. The ERC panel was one of two showcasing the value of curiosity-driven fundamental research to respond to global challenges.

Following the panel, Professor Balpreet Singh Ahluwalia at the Arctic University of Norway, and ERC-grantee, told Horizon that researchers globally are doing their part to address the pandemic. But, for him, the crisis highlights how frontier research is quickly able to adapt to address problems. This type of research is more important than ever, he says, and he hopes that funding is not cut.

‘Frontier research does not prepare us for one problem. It prepares us for unseen problems,’ he said, explaining that an application for research may only become evident in the future.

His research focuses on affordable photonic chip-enabled nanoscopy – in other words he works on making microscopes super-resolution (able to image things smaller than 200nm) while bringing down the cost.

Current super-resolution microscopes – the technology that earned a 2014 Nobel prize – can cost close to €500,000 and need to be housed in a special facility, while regular or fluorescence microscopes can image to about 200nm and cost between €20,000-50,000, he said. And that’s not good enough for the coronavirus, which is about 150 to 200nm.

When the pandemic hit, he and researchers from Norway and Germany collaborated on an open access microscope that would be small enough to use in a biosafety cabinet to make images or videos of the coronavirus. They combined a laser-printed microscope controlled by a mobile phone with a photonic chip for super resolution to make a nanoscope that costs about €1,000. Prof. Ahluwalia said their microscope is now being used by researchers in Germany and could be used in diagnostics in the future. ‘(Coronavirus) has to be addressed globally, so a technology has to be with a price tag which can be globally affordable.’

‘Frontier research does not prepare us for one problem. It prepares us for unseen problems.’

Prof. Balpreet Singh Ahluwalia, Arctic University of Norway

Blue-sky research

At an R&I days panel on 23 September, Nobel and Kavli prize laureates discussed the role of this type of basic or so-called blue-sky research in both the current coronavirus response and in helping us prepare for an uncertain future. They spoke about the lack of data to understand the economic implications of the pandemic on society’s poorest, whether we’re due for a great reset and why coronavirus should not eclipse other great challenges.

Kavli prize laureate and astronomer Professor Ewine van Dishoeck, said that research is about going into the unknown, and this approach is important for training young scientists to be independent, creative thinkers.

The major challenges of today, from climate change to the pandemic, require us to take a step back and look at them from the systems level, she said. And fundamental discoveries and technologies are there to be developed through curious thinking into solutions, she said, citing how WiFi, for example, emerged from astronomy.

As science plays an increasingly visible role in our lives, Nobel prize laureate Sir Peter Ratcliffe wants to see frontier research become more persuasive and for the broader public to better understand how it works. For him, education is key in fostering scientific literacy within wider society to understand how scientific knowledge is created and not be suspicious of it.

‘I would like to see a greater emphasis in history (lessons), on teaching history through science, and in science (lessons), teaching science through history,’ he said. ‘At that point I believe I would be much more persuasive to the general public in articulating … how knowledge will be used in an unexpected way to create valuable, new knowledge. I think that’s the single most important point that we have to get across.’

Published by Horizon