Virologist in search of the Holy Grail

Before the pandemic, people used to give him a pitiful look when he told them he was a virologist. Today, there are seventeen million virologists in the Netherlands; research on viruses is hot. Berend Jan Bosch has been fascinated by these pathogens for years. How do viruses penetrate a cell? Why do they occasionally switch to a different host? What are their weak spots? The researchers discover another antibody with the potential to target multiple viruses.

In March 2020, you discovered a new antibody to Coronavirus - in the freezer in your lab no less. That discovery made global headlines. So what's happened since then?

'2020 was all about starting up new research projects and recruiting new researchers. We were working on a lot of new COVID-related projects at the time. Most were public-private partnerships aimed at developing solutions for SARS-CoV-2, especially new vaccines and antibodies for COVID-19. In 2021, we were more focused on all the new variants. It's great to be able to do our part.'

So you've really put virology research at Utrecht University on the map? 

'We already had a pretty strong presence, but COVID definitely raised our profile. Veterinary Medicine already has a long track record in terms of coronavirology. We've been doing cutting-edge research on coronaviruses since the 1970s, building on our colleagues' legacy. The division has expanded a lot since then, though. We've currently got a research staff of 50, with 20 new people.'

Inhibiting multiple viruses 

Berend Jan Bosch is clearly driven. The twinkle in his blue eyes even shines through the screen. 'I've been working to find out if we can protect ourselves more effectively against new coronaviruses for several years now. For example, is there potential for broad-spectrum vaccines or therapeutic antibodies that can inhibit not just one variant of the SARS coronavirus-2, but several variants or coronaviruses at once. Those types of antibodies are much more versatile.'

The Utrecht-based virologist and his colleagues are focusing on less variable parts of the virus. 'We have been studying parts of coronaviruses that have stayed well preserved over the course of the evolutionary process. In the process, we discovered a new antibody in collaboration with Harbour BioMed and Erasmus MC. In addition to binding the current coronavirus, this antibody can also bind MERS coronaviruses and other coronaviruses that aren't actually that closely related.'

We're trying to outsmart the virus and improve on our own immune systems

So what did you discover?

'All these viruses have a vulnerable spot that the same antibody can attach itself to. That's a genuinely new discovery, and one that was previously considered impossible. The antibody has an even broader scope than the one we discovered in March 2020.' The study was published in Nature Communications. 'This 'primal' part of the virus has remained well preserved, possibly because it is less visible to the immune system. This means the virus is under less pressure to modify it. That offers a great starting point for the development of broad-spectrum antibodies that can prevent or fight infection by these viruses.'

So you're trying to outsmart the virus?

'That's right, we're trying to outsmart the virus by developing antibodies that outperform the ones in our own immune system. That's actually feasible, because our own antibodies only come in one format. A typical antibody has two arms with which it can bind itself to a virus, but we're trying to create antibodies that can bind to multiple parts of the virus with multiple arms. This increases their broad efficacy and effectiveness.' 

As Bosch explains, Omicron proved to be a real game changer. '95% of current antibody therapies have been rendered useless because of all the mutations that Omicron has accumulated in the spike protein. That means we should focus on the places where the virus mutates less easily, which is exactly what we were focusing on prior to the outbreak of COVID-19. Our research has only become more relevant, in other words.'

How about your workloads? Have you been under a lot of pressure? 

'We were under a lot of pressure during the first year of the pandemic and didn't have much time to relax. There weren't that many researchers working on coronaviruses around the world before SARS-CoV-2, so we were constantly being called upon. Hundreds of new researchers have joined the fight since then. I managed to get back to my old hobbies like cycling in the second year. It really helps me clear my head. You can't stay productive all the time if you don't have any chance to relax.

So how do you manage to maintain your profile with so many new coronavirus virologists out there?

Laughing: 'There is a lot more competition, especially in terms of SARS-CoV-2. Still, we'll also keep focusing on veterinary coronaviruses in future. We work at a veterinary faculty and coronaviruses are still some of the main pathogens in farm animals and companion animals, which happens to be our niche. We'll also keep working on human coronaviruses and SARS-CoV-2, but we have so much in-house knowledge of viruses and collaborative relationships with stakeholders in the veterinary field that we'll continue to focus on those. That's not going to change.'

So are there any coronaviruses that can make animals really sick?

‘Absolutely. The IB virus is one of the most prominent veterinary pathogens. It causes infectious bronchitis in chickens and has been a major headache for the poultry industry for years. On the other hand, we're also still using a lot of vaccines that aren't always that effective due to the variation between these viruses, as was the case with SARS-CoV-2. Here too, we face the challenge of developing vaccines that are effective against multiple variants. Coronaviruses are widespread among mammals and poultry. We still don't know how many there are, and new ones are still being discovered. Since SARS-CoV-2, there has been a global realisation that coronaviruses can switch hosts and spread to humans. For example, a porcine coronavirus and a canine coronavirus were recently found in humans. Although they won't necessarily cause a pandemic, it does demonstrate that coronaviruses are constantly knocking at our door.'

Virology is hot…

'You're constantly looking for a scientific challenge, something that hasn't been done before. Five years ago, people would look as if they felt sorry for you when you told them you studied viruses at parties or family get-togethers. They'd quickly steer the conversation to some other topic. That's no longer the case. It's quite something to see how it's all changed because of COVID-19.'

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