'We're right to be optimistic,' says U of T epidemiologist about search for COVID-19 vaccine

Millions of people around the world are staying home as much as possible to limit the spread of COVID-19. Social distancing has brought large sections of the economy to a standstill, but it's buying precious time for health-care workers to prepare for a tsunami of COVID-19 patients.

Meanwhile, scientists are racing to develop a vaccine for the illness, which has infected nearly 500,000 people globally and counting. 

But just how far is the light at the end of the tunnel? 

Natasha Crowcroft (left), a professor of epidemiology in the University of Toronto’s Dalla Lana School of Public Health, says that experts’ estimates that it will take at least 18 months to develop the vaccine look optimistic – and don’t account for the time necessary to produce the vaccine on a global scale. 

But “we’re right to be optimistic,” she says, adding the world is making a collective effort to solve this problem. Earlier this week, Prime Minister Justin Trudeau announced that the federal government is investing $275 million in coronavirus research, including the search for a vaccine. 

While attempts to discover a vaccine have been depicted as a kind of “arms race,” it’s not a competition, according to Crowcroft. “To me, it's a win-win,” she says. “It's not an arms race against each other; it's an arms race against the virus.”

She spoke to U of T News about the pitfalls in vaccine development, how these problems have been dealt with in the past and what unexpected benefits may come from the development of a coronavirus vaccine.

What's in a vaccine?

That's quite a complex question to answer because they're made in lots of different ways and what goes into a vaccine depends on what type it is. There are many different approaches being taken for COVID-19. I think the WHO has posted more than 40 candidate vaccines on an incomplete draft list. 

It also gets complex because of the way science has advanced. Using an inactivated virus is a very old-fashioned approach where chemicals might be used to inactivate the actual organism. 

Or you can have a live, but weakened, version of the organism, or a live organism of some kind. But even there it gets more complex because you could either have the actual live virus – I'm not saying this is happening for COVID, but it could happen – or you have a live organism which is a different organism with a piece of the live agent in it. And then you can have the genetic material that allows the person who's given [the vaccine] to make whatever it is you think is going to protect them. That last example would be a nucleotide vaccine. That's another approach. 

Everyone is now asking how long will it take to develop a vaccine. What are your expectations there? 

I think most people are thinking it's going to be at least 18 months before we have anything possibly ready for scale up, if you want a number. 

But I think the honest answer to that question is we don't know. There are so many steps in the process of producing a vaccine. Like your question about what kind of vaccines are there? That first bit of figuring out which antibodies protect people, then figuring out how to make something that helps people make those antibodies -– that whole process – that's just the very first step in the whole thing. 

There are multiple steps that have to be gone through, and vaccines can fail at various stages. You can make what looks like a perfect vaccine that an animal makes antibodies [in response] to, but you put it in humans and they don't make the right kinds of antibodies. Or you can make a vaccine that seems to work perfectly in making the right kinds of antibodies, but it has side effects that are not tolerable. Or you can make a vaccine that seems to make the correct kinds of antibodies, but, actually, when you give it to people, it makes the disease worse in some people. That's rare, but we've seen it with Dengvaxia, the dengue vaccine. If it's given to people with no antibodies to a previous infection, they get increased problems with dengue. 

At every stage, things can go wrong. The most common problem might be that it doesn't work. And you don't really know that until quite late in the process, which is another reason it's very hard to predict right now what's going to win this race. 

The number one question [for a vaccine] is: Is it safe? Number two is: Does it work? They're both needed, but you focus on the safety before you go to the next stage at each step. 

At the very end of it you have to scale up. You have a vaccine that's safe and looks like it's been effective. Then you have the practical problem of scaling up production to seven billion people on this planet, potentially. That last part is not a scientific challenge, it's a practical challenge, but it adds time to the whole process. 

Then you have to evaluate at the end of it, how it is working in the field. The great thing is that lots of different approaches are being tried. I really hope that a lot of different vaccines make it through to the end because, even if we have something that looks really good in trials, we don't know until we use it in the field how good it is. 

The more vaccines make it through to the end, the better off we are. 

Can you elaborate on the hurdles in the process of making a vaccine? 

The biggest hurdle, really, is [moving it beyond] an idea that somebody has in an academic centre like the University of Toronto. Some researcher could have a great idea and do really interesting preliminary work. There are people at U of T who are doing really great work on thinking about how you might make vaccines to various pathogens. But the biggest hurdle for vaccines is between that preliminary science through to the point where you can start thinking about using it in the field. They call it the “valley of death.” Somebody who has what looks like a promising vaccine needs to get in position where someone else could maybe market it in order to get it through testing.

It's incredibly expensive: all the animal studies you have to do to prove safety; all of the phase one studies that you have to do in small numbers of people; then phase two studies, then phase three studies in the target population. 

You go through this process trying to get a vaccine to the point where you can get approval from a regulator like Health Canada or the FDA in the U.S., whichever regulator you need to go to. That is the hardest part.

Now, you have this global effort to move things along. The WHO is really trying to facilitate that and then also there's an organization called the Coalition for Epidemic Preparedness Innovations, a global initiative to try and protect the world against exactly these kinds of threats. 

Are vaccines not very profitable? Is that why more companies don't move into this field until there is a crisis? 

If you take the example of the coronavirus vaccine, it's not a hypothetical. Or the Ebola vaccine. Why would a private company invest in a vaccine that would have no real market [before a large outbreak]?

The question isn't really whether vaccines in general are profitable because I think it's perfectly possible to make a decent profit making vaccines. If you're running a business you can make a lot of money selling high-risk things, but you can also make a lot of money selling things like vaccines that are a low risk because you know exactly what you're selling. It's a fairly safe bet. If somebody can't make a decent profit from vaccines then they're doing something wrong. 

I don't think that's the issue. When I say, “make a decent profit,” I mean decent in the sense that you're doing a good thing and you're being paid reasonably for what you're doing. I think there are whole areas of our economy that are not about making something well and meeting a need. They're just about making a lot of money from risk – more like gambling. 

Pharma isn't perfect. Everyone knows that. But when you're making vaccines, you're actually doing a good thing and making a decent profit. But when it comes to vaccines for emerging infectious diseases, you don't know when they're going to emerge and you don't know how big the issue is going to be. 

Canada had an Ebola vaccine 10 years before the big Ebola outbreak in West Africa, but they hadn't scaled it up or tried to put it into production. At that point, the largest outbreak of Ebola had been a few hundred cases. And it wasn't until this huge outbreak happened that everyone woke up.

From an ethical, moral imperative, that vaccine should have been developed and if Ebola outbreaks had been happening in North America then that vaccine would have been put into production. But they were happening in a poor setting where governments would never be able to afford to scale up production of a vaccine like that. It wasn't until that massive outbreak in West Africa that was starting to threaten other countries that the world woke up and took action. 

The Ebola virus vaccine was approved last December even though the disease has been around for decades. So, with that in mind, is the experts’ estimate of 18 months for a coronavirus vaccine realistic? 

It might be optimistic in terms of the scale-up. It's already optimistic in the sense that it took 10 years to develop that Ebola vaccine and it was used in the 2015 outbreak. You were talking about the official approval process, but [the vaccine] was used in the Ebola virus outbreak in the pre-approval stage. But the thing that triggered the development of an Ebola vaccine in Canada was 9/11 – the threat of it being used as a bioterrorist agent.  

It's brutal, but, honestly, it's been very hard for a mixture of reasons, including racism and power relationships and the history of colonialism and structural violence and everything else. It's been very difficult to get people in high-income countries to take outbreaks in Africa seriously. 

The entire power of vaccine science has been swivelled to produce a coronavirus vaccine right now when it could have been done a long time ago. It's because this is a threat to us now. And there's been lots of work on influenza because everyone thought it would be an influenza pandemic that would do this, but it turned out to be a coronavirus. 

What are the politics involved in discovering and developing a vaccine? Because you see this issue discussed in the media as a kind of “arms race.” 

Yeah, I don't know if that's a very good analogy. It's an arms race against the enemy of coronavirus, but it's a bit misleading because it sounds like an arms race between countries as well. The Cold War-type analogy doesn't really work. 

In terms of the science side of it, if we produce more candidates we're better off, not worse off. We really won't know which is the best vaccine until far down the line. If we end up with several that look good, let's use all of them. 

It's a bit like the influenza story. We actually need lots of different kinds of vaccines. We have a live influenza vaccine that works best in kids, high-dose vaccines for seniors, vaccines that are produced in different ways, with different numbers of components. It may be the same for COVID-19 and turn out that one vaccine works better in older people and another vaccine works better in younger people. We really don't know what's going to come out of all of this. To me, it's a win-win. It's not an arms race against each other, it's an arms race against the virus. 

What else may come from this global push to develop a coronavirus vaccine?

Every time there's a crisis it brings out people's ingenuity. There may be all sorts of benefits that we can't anticipate right now from solving this problem for vaccines in general. It may also help fix the issue of vaccine hesitancy because people will realize just how important vaccines are. But who knows what will happen?

Is there anything else you want readers to know? 

I think the last thing I want to say is: People are saying 18 months and I think that is, from what we know in the past, optimistic. But I think we also have to be optimistic and the world is different now from what it was in the past. All sorts of things have happened to put us in a better place now that we were before to respond to this kind of thing. 

Science moves forward. We have governments that recognize what's going on. These governments are taking this seriously, so I think it’s right to be optimistic.