Q&A with Brett Finlay on vaccine development

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Back in 2002, in the midst of the SARS pandemic, B.C. researchers like Peter Wall Distinguished Professor Brett Finlay were among the first to sequence the SARS genome and develop containment strategies.

Finlay, a professor in the Michael Smith Laboratories and in the Departments of Biochemistry & Molecular Biology and Microbiology & Immunology at UBC, is now part of a committee to advise the province on COVID-19 research priorities. This committee, coordinated by the Michael Smith Foundation for Health Research, will help answer questions like: What does the science tell us about how to ease restrictions? What can we learn from the way other countries have responded?

The Peter Wall Institute caught up with Finlay to talk about his involvement in the development of three potential SARS vaccines, and how that experience can help inform our response to COVID-19.

The following interview has been edited for brevity and clarity.

 

PWIAS: Why does it usually take so long to develop a vaccine?

Brett Finlay: First of all, you've got to be able to sequence and grow the virus, and that's not always immediate. And then the problem is, you have to wait to see an immune response, which takes usually at least a month in pretty much any animal. After this, you have to work your way up through different animal models, and then you've got to do human trials to make sure it's safe to use in people —  what was tricky, at least with SARS, is you have to then use the vaccine in an area where the disease is endemic, in order to prove it actually works. That was hard in SARS because we didn't know where it was going to flare up. And then you've got to do all the safety requirements associated with it.

The bottom line is if you put the pedal to the metal, I guess you could probably get something to market within a year; this is about as fast as you can do it.


PWIAS: What was the response during SARS to develop a vaccine?

BF: Before SARS — because SARS is a type of coronavirus, just like COVID is — there was very little interest in this virus. There's five or six kinds of corona viruses, and they usually cause mild colds in people. But there's zero interest in it, and there's only about three or four coronavirus experts in the world. And they had developed vaccines successfully for animal coronaviruses. When SARS hit, no one knew anything about coronaviruses. But then, as you can imagine, when it hit, just like COVID now, everyone in the world was all over it and throwing money at it. However when SARS did not come back the next year, enthusiasm went out the window and rightly so — people moved on to other things.

Now, [with] COVID-19, my guess is it's probably going to be here for the long term, and so I think there's significant market in terms of a vaccine. But let's pretend you made a wonderful SARS vaccine the first year we had it, and then it never came back. And, you know, making vaccines is a $200 million to billion-dollar investment to get it out to the public.
 

PWIAS: What are the components of a faster response learned during or since SARS?

BF: In science, normally, you take it one step at a time. In SARS, what we really learned is you should do things in parallel. You have already started to figure out where you're going to do the field testing sites and what the animal models were, while you're still just trying to grow the virus. So working in parallel can really decrease and streamline your timeline. Instead of having to wait for one thing to do the next things you assume you're going to get that, and then start down the line.

And you need to have it all mapped out: 'And we're starting to do that now; let's pretend we have a cold virus in three months; how are we going to test it? Where are we going to test?' So those scenarios are already planned and modelled and being done — as opposed to, wait to develop a vaccine, then ask, 'Where do we test that kind of thing?'

There were major hurdles too. First of all, our system is not built for rapid vaccine development, it's very slow, methodical, proving it's safe one step at a time, and it usually takes 10 to 15 years to get a vaccine approved. So you are fighting the standard regulations — they're there for a reason, for safety — but they're very difficult. One thing that you can do is, you can actually go straight into humans if you can prove it works in two relevant animal models — the 'two-animal rule' — if the circumstance is really dire.

Ironically, the thing that we suffered the most with SARS, were the lawyers' legal agreements: who owns the vector, who owns the rights to this, who owns this, which university gets all the patent rights to it? Of all the issues we encountered, that one, frankly, was the hardest and we could not solve it. So we just went around it and built a vaccine and said, 'Well, if people are dying of it, the lawyers will figure it out.' We couldn't get around the legal aspects of it. We just had to end-run it.
 

PWIAS: Are there other lessons that can be taken from that development process and applied to COVID-19?

BF: Technology has changed since we did SARS; you can go a lot quicker with RNA and DNA. But the same old issues still apply. The other weird thing is you're dealing with the immune system and we cannot predict what is going to make a good vaccine. It's really a lot of trial and error. You think, well okay, we have MERS we have SARS and COVID-19; we've got all these respiratory coronaviruses; we've got animal vaccines to coronaviruses — why can't we just have a generic coronavirus vaccine and whatever pops along we just insert this cassette in there for the current virus and away we go? Unfortunately, the immune system doesn't work like that. And so we haven't been able to do those things.

You have to look at all the steps: where can they be sped up? Can we be proactive and have [processes] in place, like a clinical trial centre ready to go when the vaccine comes online, for example? Who's going to produce this? How do you scale up to vaccinate the entire world, pretty much overnight? These are the kind of issues you have to deal with.
 

PWIAS: Do you have a gut feeling as to what our best shot will be, in terms of techniques or approaches to developing a coronavirus vaccine?

BF: Well what we did with SARS, which no one else I know of in the world did, is we didn't pick any one particular [approach]; put all our money in one. Instead we tried three parallel strategies to see which one would get us there. We were able to compare those three strategies head to head so we had a much better idea at the end of six months which technologies were actually going to work better. So who knows? I mean they're trying RNA vaccines now; there's no approved RNA vaccine out there but they're trying that. Unfortunately you just can't pick a winner in terms of gut feelings. The best thing is, you try them all in parallel and you compare and contrast, and pick the best one.