Epidemics, and even pandemics are occurring at an accelerating pace. And we anticipate
to see outbreaks every year or two. So our laboratory has been orienting toward a rapid
discovery program, where we can respond immediately and seek antibody treatments or preventions
in real time, as they happen. We've been prototyping this in previous epidemics. We've been preparing
for this moment, and now we're activated around responding to a coronavirus.
Hi, I'm James Crowe. I'm Director of the Vanderbilt Vaccine Center.
Dr. Crowe is part of a special team of experts, universities,and advanced genetic sequencing
groups that are trained to deliver rapid treatments in the midst of an outbreak.
It was a concept launched back in 2017 by the Defense Advanced Research Projects Agency.
DARPA usually puts out calls for research about things that can't be done right now.
They pitch a vision for something that is desirable, it's an aspirational goal, sort
of crazy ideas. So the pandemic prevention program, or P3,
the idea was an epidemic occurs, and in 60 days, groups would take blood samples, and
be ready to treat people 60 days later. Normally, drug programs take a decade, or certainly
years. So it was a crazy idea. Last year, we did a simulation in which we pulled the
timeframe down to about 78 days. So we were pretty excited about that success,
and it's the fastest anyone has gone from a blood sample to an antibody cure. That we
know of. And we were just simulating last year.
But this year, we're doing it for real. The goal is to safely develop an antibody
therapy that can provide immediate immunity, potentially before a vaccine is ready.
The clock started to tick once this coronavirus outbreak switched from epidemic to global
pandemic. The pandemic started in China, and certainly
we knew in December that something unusual was going on there. But it wasn't clear in
December 2019 that this would spread anywhere else.
By January, the first case occurred in the United States. And by then, our team got concerned
that we really needed to activate around this. Fortunately, as soon as the outbreak occurred,
the sequences of the virus were published. It's an RNA virus. And we know that there's
only one major protein on the surface of the cell, and it sort or looks like spikes, so
people have called it the spike protein. And we know that's what attaches to your cells,
and attacks you and inserts the virus in. Your body has an immune system, and it responds
to threats in various ways. The principal way after you're infected that you prevent
the infection from occurring again, is through a network of proteins in your body called
antibodies. Once you've seen a virus, like coronavirus or flu, you remember that virus
when it comes back. You already have antibodies, and they're sort of a shield.
So the idea is, if we have antibodies that can attach to the spike protein and cover
the virus, it'll block the virus from being able to get in.
So we know what we're looking for. We want antibodies to that spike protein.
To find antibodies, they need to secure blood samples from patients first.
We actually contacted the providers, the medical teams who were taking care of the first cases.
And in fact, the sample from the first case in the United States came to us through that
network. There's a cloud of chaos around these cases.
There are family members, and press, and lots of people in PPE. It's actually hard to get
the communication to the subject themselves, or their families. When we do that, almost
invariably the people say, "I would love to contribute. I would not want anyone else to
go through what I went through." These are important samples.
We've been working with FedEx Critical operations, and they've been essential to our success.
So not only just barcoding like they normally do. We could watch. The package goes into
the truck, and it's coming toward us, so we go "It'll be here in 30 seconds."
We do whatever it takes to move this stuff around. But we do it safely, but we're tracking
everything very carefully. We start with whole blood. It's got a lot
of red blood cells, which carry the oxygen and the white blood cells. And so we pull
the white blood cells out, and those are the immune system cells. And there are the B cells
for antibodies. And so we pulled those out...It's like a needle in a haystack, we know a few
of those in there are for the recent infection, like coronavirus.
And so that's where the high technology comes in, is drilling down and finding the individual
cells that make an antibody. Now we have a little cell, and it's very fragile,
very small, and we have to manipulate that, and get it to make the antibody and confirm
yes, I'm a coronavirus cell. At which point, we bust the cell open, and
inside that are the genes for the antibody. So we recover the genes from a single cell
and we just sequence it, and we can print the gene out in a DNA printer. The machine
gives us the DNA back. It's pretty amazing. That's come out of a revolution in science
called synthetic genomics. So you can synthesize DNA, at very high scale.
Then we can put that back into a cell in the laboratory, and that cell becomes a factory
to make that antibody. Then we have lots of the antibody, which is
a protein we can give to people and protect them.
So there's a lot of steps involved, and some of its conventional, but some of it's magical
We run into obstacles. We have to overcome those obstacles immediately, like within minutes
sometimes. We have about four or five thousand antibodies
in our pipeline now, that we've gotten from single cells from survivors and then we'll
down-select. We'll look at about 20 of them in mice. And
then we'll end up with two of them in monkeys, and we'll be done. That’s the sprint. The
first human trials of any antibody are likely to be in the June to August window. And that's
when we just put antibody into 20 people, and make sure nothing bad happens. And then
there's a next step where we need to figure out, what's the dose? So usually we give 100
people a dose, another 100 people a lower dose.
And then finally you do what's called a phase III trial, and you figure out if it works.
And that's thousands of people. If the antibody works, and we already know it's safe, then
it would be released to the public. That's going to take an uncertain amount of time.
Probably year, year and a half before it would fully be released to the public, because we
have to do this methodically. And you could say, "Well you have it, just give it to me.
Why don't you just give it to me?" But, some treatments make people worse. Hopefully by
public health measures, social distancing and that sort of thing, we slow things down.
It'll remain to be seen whether this becomes a winter thing, and we have a whole nother
season. That's why everybody's pushing. It's interesting to watch our team operating, because
they're kind of in a flow state. These guys are working about 20 hours a day since January.
But at the same time, they're actually doing the work at an unprecedented pace for something
that's killing thousands of people. So there's a passion and a mission in it. Scientists
typically are very methodical. They like to repeat things, they like to be sure. They
don't like to tell people the result until they've done it more than once. And in this
type of science or discovery, we can't do that. And we're constantly trying to retrain
ourselves to think more like. You know, what's good enough? What's the 80% solution? We got
to move forward. And it's not natural to think that way.
Coordinated response teams that can deliver rapid therapies will be a critical component
in future pandemic preparedness. But how can we get ahead of this next time?
You cannot pick the next one. You can't predict, "I know it's going to be a filovirus, or a
flavivirus, or an alphavirus. But you know one of them is coming.
And what we've been advocating is, why don't we get antibody cures for all these teed-up
ahead of time? And when it happens, we don't have this scramble.
So we've been methodically making antibodies. And we're about 40 into it. We have antibodies
to other coronaviruses. But they don't cross-react with this one. But I think preparing ahead
of time makes more sense than always waiting.