Nikhil: At the Crick, I develop antibody assays, tests that look for the presence of certain antibodies in a sample and examine the antibodies’ behaviour. Very early on in the pandemic – before it was even classed as a pandemic – Kevin came to me and suggested that we repurpose one of my assays to look at the immune response to SARS-CoV-2, the virus behind COVID-19.
Kevin: The genesis of the project really came from Nikhil’s assay. We realised early on that we might be able to use our existing lab skills and techniques to study this virus. Once you’re able to look in detail at the way that the immune system responds to the infection, you open up a whole new field of research into this coronavirus and how it behaves.
Nikhil: We have developed a very sensitive assay that can detect antibodies that attach to the SARS-CoV-2 spike protein. We’ve found these antibodies in people that have had the pandemic virus, but we also found that some people that have had certain common colds have antibodies that also bind the SARS-CoV-2 spike.
In a separate test, we have found that these antibodies from the people who have had specific colds can neutralise a virus that uses the same spike protein as SARS-CoV-2.
It shows that some people may have some immunity to the pandemic virus already because of colds that they’ve had in the past. The assay itself could also become important as an extremely sensitive testing method, and a way of researching the virus.
Nikhil: I’m interested in the viruses that are modified and repurposed to deliver gene therapies. These viruses (or ‘viral vectors’) are tools that are used to get inside patients’ cells and insert genes to treat diseases, but we need to know more about how our immune system responds to these viruses. I create assays to study the immune response, and that’s the part of my work that played a role in this new project.
Kevin: I study a class of immune-modulating drugs known as immune checkpoint inhibitors, which boost the immune system’s response to diseases like cancer. I’ve recently been studying their effect on a class of immune cells called B cells, which was lucky timing as these are the cells that produce antibodies.
Kevin: No – not at all. Doing a PhD can be difficult because you often have to wait years to see the benefits of your work. This project could have an immediate societal impact. It’s definitely an interesting time to be a viral immunologist.
Nikhil: Exactly. If there was ever a time to put aside your own project and focus on how you can help, this is it. Because of our previous work, we were well-equipped to study the immune response to the virus and there was never a question of not doing everything we could to help.
Kevin: It’s been a complete transformation. Normally, I would be working on a project for five years before publishing results. Now, everyone is sharing little ‘vignettes of information’, sometimes literally minutes after they’ve collected the data. It’s broken down a lot of barriers, and it feels like the scientific community is working more closely now.
Nikhil: Definitely. We’re working with teams at the Crick and around the world that we wouldn’t normally interact with. The project has been a real collaborative effort and we’re working with different labs at the Crick, as well as the flow cytometry, proteomics, structural biology, and cell services facilities and University College Hospital.
Kevin: The sense of urgency around the pandemic means that it makes sense to work together and to use tools like preprint servers and social media. This has the added bonus of working towards democratising science, as we no longer have to wait years to share results through established journals and conferences.
Nikhil: I’ve never seen people so motivated and driven. The speed at which we’re working means that we have to be dependent on one another and trust the people we’re working with. There literally isn’t time for one person to do everything themselves, so you have to communicate with the whole team.
Kevin: It’s true – everyone is responsible for their own section of the project, and we all have to trust that everyone else will be taking care of their sections. It’s meant that you have researchers at all career stages working alongside each other.
Kevin: One unexpected issue was a lack of samples from people confirmed to have the common cold. You usually don’t get tested if you have a cold, so those samples were actually much harder to track down than the coronavirus samples!
Nikhil: There are two main things that this assay could be useful for – diagnostics and research.
The assay is very sensitive and when we know more, it could potentially be used to check the immunity of people like frontline NHS staff. However, we would need to carefully compare it to the other serological tests that are out there and find ways to scale up the process so that we can carry out a significant number of tests.
Kevin: There are lots of different ways that the assay could be used in research as well. We’re still deciding how to best use it, but major outstanding questions from our research include the immune response in young children or other groups that are frequently infected with colds. We’re also interested in tracking how long immunity might last after infection. These could both help to inform policy decisions in the near future.
Kevin: We know that we’re extremely lucky to be able to do this research. It depends on a huge number of people and facilities and I know that it wouldn’t be possible at every university and research institute.
I hope that this pandemic goes some way to showing the value of basic research to the public and to policy makers, because when this is all over, we’ll still be here studying all the other diseases that are still affecting people around the world.
