COVID vaccines were made in record time. Meet a scientist who made that possible

It’s been a difficult year for most, and utterly heartbreaking for countless others. COVID-19 has claimed the lives of more than 22,000 Canadians. But hope, in the form of vaccines, is finally in sight.  

And while these vaccines are a testament to what science can do quickly, it certainly didn’t happen overnight. Most of these vaccines are based on discoveries that happened years ago.

Dr. Jason McLellan is one scientist who was integral to these discoveries. He spoke with Quirks & Quarks host Bob McDonald about his fundamental research pinning down the notorious viral “spike protein”  that made the current COVID-19 vaccines possible. Here is part of their conversation.

So tell me about the moment when you first heard about this new coronavirus. What was your reaction? 

I first heard about it while I was on a snowboarding trip with my family in Park City, Utah. And I got a call from my collaborator, Dr. Barney Graham, at the Vaccine Research Center at the National Institutes of Health. And he told me that this new pathogen causing pneumonia outbreaks in Wuhan was a coronavirus, and likely similar to the first SARS coronavirus that emerged back in 2002. And he said he wanted to put a team together to continue the work we had been doing on coronaviruses and rapidly produce a vaccine.

So was it sort of a here we go again moment for you? 

My lab had been working on coronaviruses specifically with a focus to try to understand the structure and function of some of the viral proteins, particularly the large protein on the surface of the virus. That’s called the spike protein. 

And we had come up with methods for stabilizing it, locking in certain confirmation and using that as a vaccine antigen. So we actually had a lot of information available on how to make the best possible coronavirus vaccines. 

This is a 3D atomic scale map, or molecular structure, of the novel coronavirus spike protein, as described by Jason McLellan’s lab.(University of Texas at Austin)

Tell me a bit about what those spike proteins actually are, and how they work. 

So these are club-like molecules, like a mushroom shape. They perform two critical functions for the virus. The first is attachment. The virus has to stick to our cells. And if we think of it as a mushroom, the cap of that mushroom binds to a specific protein on the surface of our cells, so that allows the virus to stick to our cells. 

And then that process, the receptor binding, causes the cap to fall off, and the stalk that’s left elongates and actually shoots into our cell membrane and then folds back in half on itself like a hairpin, and it brings the viral membrane and the membrane of our cell together to fuse. That way the genome of the virus can enter our cell, reprogram our cell to start making more copies of the virus. So it’s really critical for that attachment phase and the entry phase. 

So we want our vaccines to recognize these spike proteins. Why is that hard to do? 

Well, the spike proteins can undergo conformational changes, as I mentioned, the cap falls off, the stalk of that mushroom rearranges. And so when we think of designing a vaccine, we have to think of what form of the protein do we want to present to our immune system. And ideally, we want our immune system to be trained to recognize the mushroom shape of the protein as it exists on the surface of the virus. Not any of these other forms, or forms of the spike where it falls apart or changes confirmation. And so we have to come up with methods to try to stabilize the spike protein and keep it in that same shape as it appears on the surface of an infectious virus. 

For future coronavirus pandemics, the entire field of science is much better prepared.- Dr Jason McLellan, associate professor of molecular biosciences at the University of Texas at Austin

If you want to recognize these things but they keep changing shape, how do you know what they look like in order to to create a vaccine for them? 

Yeah, so that’s what my lab and others have done. That’s a field of science called structural biology. And we’re able to determine very high resolution images, blueprints of these proteins. This allows us to ultimately make a 3D print that we can hold and look at. And having that type of 3D print allows us to go in and make changes, to introduce like a molecular staple that locks two regions of the protein together. So it’s a very rational engineering approach once we know what this spike protein looks like at high resolution. 

How long did it take for you and your colleagues to do this work so you could respond so quickly? 

We started working on coronaviruses back in 2013 and it took four or five years for us to determine the structures of these spike proteins, design stabilizing mutations, test these modified spike proteins in mice to measure their immune response. So there’s always a lot of failure in science, but overall, about five years of research. 

How hard was it when this new virus appeared to figure out how to freeze its particular shape?

Actually we were done within an hour or so. Just because the spike protein on all the different coronaviruses are similar in shape, particularly in this one region, all we needed was the sequence. 

A health-care worker looks at a dose of the COVID-19 vaccine in Montreal. (THE CANADIAN PRESS/Ryan Remiorz)

How many vaccines are using your technique? 

The Johnson & Johnson vaccine, Moderna vaccine, Pfizer-BioNTech vaccine and Novavax. And there are others on the way. And we’ve actually developed a second generation spike protein that’s even more stable and that’s starting to be used in some second generation vaccines, and vaccines in the developing world, with a phase one actually that’s going to start next week. 

Does it work with the new variants as well? 

It does. And the changes we introduce are in like the stalk portion of the spike protein, and many of the variants, the changes we’re really concerned about are in the cap portion and so we can easily make these variant spikes in the stabilized form. 

Now that you have this fundamental knowledge of how these viruses work, what does this mean for future viral pandemics? 

For future coronavirus pandemics, the entire field of science is much better prepared. We know exactly how to stabilize them. We have demonstrated efficacy of mRNA vaccines, for instance. And so if there’s a new coronavirus outbreak in a decade from now, I think we can move even faster than we did this time. 

And now my lab and others around the world are also thinking about how to develop a universal coronavirus vaccine. 

What about vaccines for viruses that are not coronaviruses? 

I think what we’ve shown is the power of structural biology, this idea of being able to determine high resolution structures of these important viral proteins and then use those structures to engineer optimal vaccine antigens. I think we’ll see more and more of that apply to a variety of different pathogens, not only viruses, but also parasites, malaria, bacteria. So I think it’s going to be a very powerful tool for future vaccine development in general. 

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