2020. március 16., hétfő

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Since Thursday evening, the article by a team of ten scientists, of which Grosveld is a member, has been online on BioRxiv – a website where biologists can publish their research before it will be assessed by the prestigious journal Nature. In the summary, the scientists describe an antibody to SARS2, the coronavirus causing the current pandemic (COVID-19). The antibody can help detect and prevent this type of corona infection. It is a world's first.

Disclaimer: The antibody still has to be tested on humans (and this will take months) and the article is under peer review before Nature will publish it. But Grosveld is hopeful: "We expect an email any moment", says the Spinoza Prize winner in his lab on the tenth floor.

What did you and your fellow researchers from the Department of Virology and Utrecht University find, exactly?

"We have published an article about an antibody that we had already isolated before the current pandemic and which cross-reacted (biological term for repelling a foreign substance, ed.) with various coronaviruses. The antibody prevents the virus from being able to infect and can also help in the detection of the virus."

How did you discover that?

"About fifteen years ago I started a hobby project to see if we could make human antibodies (proteins made in response to antigens such as viruses, ed.) in mice. That succeeded and eventually led to the establishment of an Erasmus MC company: Harbor Antibodies BV. We now have branches in Shanghai, Boston and Rotterdam where the innovation branch is located. They mainly develop antibodies to cure tumors."

"Together with the Viroscience department upstairs and the Virology department of the Veterinary Medicine Faculty at Utrecht University, we joined a European project: ZAPI (Zoonosex Anticipation and Preparedness Initiative, ed.). The aim was to develop antibodies against MERS, SARS and another Hongkong coronavirus (OC-43). In that project, we found antibodies that cross-reacted with those three different viruses and kept them from infecting.

"But those viruses have already been contained, we are now dealing with a different coronavirus. We still kept untested antibodies from the previous study in the refrigerator that did not react with all three mutations, but did with SARS1. When the current crisis – SARS2 – broke out, we immediately tested whether the antibodies that reacted with SARS1 also responded to SARS2. We then found the antibody that has now been published."

What are next steps and what can we do with them?

"We are now trying to get a pharmaceutical company on board – which is looking promising, by the way – that can produce the antibody on a large scale as a medicine. Before it can be marketed, the antibody must go through an extensive development phase and be tested for toxicological properties. That process is now underway. In addition to the development as a medicine, we also want to use the antibody to set up a diagnostic test: one that everyone can do from home, so that people can easily find out whether they have an infection or not. "

kantoor Frank Grosveld Erasmus MC
Image credit: Marko de Haan

How unique is this find?

"As far as we know, this is the very first antibody that blocks the infection. And there is a good chance that it will also become a medicine on the market. Finding something like this is very rare. During my career I have worked a lot on gene regulation: how are genes switched on and off, what is the structure of our genome? Fortunately, I was also able to make a number of discoveries in that field that made me feel we were really making progress. But such research was mainly about understanding and out of scientific interest. This antibody is all about application."

So you now have the solution?

"If you were to take this as a patient, it is expected – only an expectation right now – that the infection will be stopped. And so it can give the patient an opportunity to recover. But prevention is of course better than a cure: a real solution is therefore a vaccine, others are working on that. However, developing a vaccine can easily take two years. Our medicine, if it all works as it should, could be here sooner. But it will be more expensive to produce.

"A vaccine usually consists of a protein that comes from a virus or a killed virus. If you put a little bit of that in people or animals, they will make antibodies against it. This creates so-called memory cells that remember what they've seen before. If the virus tries to enter the body, those memory cells can respond quickly to it and ward off the virus. An antibody acts as a medicine, but the patient doesn't make antibodies himself. If you administer the drug it will last for a few weeks. That's enough for recovery, but probably not to keep the virus out forever. It's better if the patient develops his own immunity."

Did you immediately think 'I may have something for this' when this virus broke out? How does that work?

"My colleague from Utrecht Berend-Jan Bosch and I thought: we have to do something and maybe we've got something for it. That is why we started immediately and the current panic means working hard around the clock. I start at about nine, until about seven. Then I go home to my family and when everything has settled down there I start working again, until just after midnight."

Have you already received a lot of attention for it?

"Not so much yet. It has now been published on BioRxiv, but it is only for real when it has been approved by the peers at Nature – until then we are not allowed to go to the press on our own. But if you ask questions, we can answer them. Hopefully the approval will come in a few days and then Nature will also send out a press release. You can see that the publication on BioRxiv is already provoking something among colleagues on Twitter and LinkedIn. Yesterday I already received a record number of emails and texts."

Are you going to be rich thanks to this find?

Laughing: "You see that all wrong, this isn't a good business case. There is a chance that the virus will be gone in a month or two. Then as a pharmaceutical company you've spent millions for nothing – only they are able to take these kinds of risks. There was also a panic when SARS1 and MERS broke out. By the time there was a vaccine and antibodies, the virus was already gone."

uitzicht laboratorium frank grosveld erasmus mc
The view from Grosveld's office Image credit: Marko de Haan

What do you think of the current approach in the Netherlands?

"We have been too lax and were not well prepared. For example, there were too few tests and too few restrictions in the beginning, while we could see what was happening in China and then Italy."

Will the test you are developing solve some of this?

"We would love to do that and a cheap first test has already been produced in China, but I don't know how much they are able to create. I've asked them to send some tests here to try them, but the ban on flights from China is making that difficult. Making a test can be faster than developing a medicine, because such a test doesn't need to be researched as thoroughly as medicine. It is not something that you administer to a patient and works pretty much the same as a pregnancy test, except with oral mucus instead of urine. I don't know how much the test will cost in the end."

Were you lucky or clever to make this discovery?

"In our first study with SARS, MERS and OC43, we did a clever job – before this crisis broke out. And later we were lucky to have antibodies that also bind to the new virus. We were therefore ahead of others, but undoubtedly more antibodies against SARS2 will be developed, also by us."

tentamenzaal-erasmus-universiteit

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