NEWS REPORTER: Officials in China say a virus which has killed
nine people has the potential to spread further.
In different corners of the globe,
a small band of scientists had, for years, been preparing
for this moment.
We knew it was going to happen - it was just a question of when.
A virus can get from one corner of the world
all the way to the other side of the world
in less than 24 hours.
Tasked with the seemingly impossible...
What's happening? You got all the bloods, eh?
..suddenly, the fate of the world was in their hands.
NEWS REPORTER: Fears are growing that it won't be possible
to stop the global spread of coronavirus.
Covid-19 is our absolute worst nightmare.
Right now, there's one thing all eight billion of us
on Earth wish for - a vaccine for Covid-19.
Vaccines have saved more lives
than just about any other public health intervention in history.
Vaccines are absolutely mission critical
in taking care of a pandemic.
Over the past year, we've been on five continents, behind the scenes
following pioneering scientists through every step,
from vaccine design...
I was right!
3, 3.5.
All right, going in now.
..through make-or-break clinical trials...
The workload and just the intensity of it,
there's just so much pressure to get everything right.
..all the way to mass manufacturing.
We currently have 200 freezers on site,
another 60 showing up today.
My team spent about a half a billion dollars
before we had any idea if the product was going to be successful.
That's crazy.
This is the story of how these vaccine scientists
harnessed cutting-edge technology never before used on this scale,
to achieve in months what typically takes 10 to 15 years.
You are so focused on what you have to do,
you do not think about anything but how to get it done.
A virus that knows no borders
is taking a worldwide effort to confront it.
There have been sacrifices along the way.
TRANSLATION:
These scientists took on one of the biggest challenges
in the history of modern medicine...
There was never any guarantee that
we were going to be successful with this, but we had to try.
..to save all of us.
It's about protecting the entire world.
On December the 30th 2019,
George Gao, one of the world's leading experts
in infectious diseases, first got wind of something
that would soon affect all of us.
TRANSLATION:
Gao's team in Beijing immediately sourced samples
from patients in Wuhan.
Thanks to the latest rapid genetic sequencing techniques,
within days, they identified what was causing the mystery illness.
A new deadly virus had never been identified this quickly before.
The genetic sequence for the new coronavirus
sounded the starting gun for vaccine scientists worldwide,
already prepared for this moment.
While Gao himself raced into vaccine development in China...
..other teams used completely different ways
of turning the virus into a vaccine.
When the sequence of the virus came out on January 10th,
we were certainly prepared and had determined exactly
how we would make the vaccine, in order to move very quickly.
TRANSLATION:
We saw the sequence, we thought, yes, let's make a vaccine,
but we'll pretend this is the real thing.
We'll get a great publication out
and, you know, we can pretend like we've saved the world.
This really went quickly, from practice
to, "Oh, shit, this is the real thing."
My brother was living in China.
I was aware of this virus that was spreading.
My phone pinged late.
It was a late Friday night, early Saturday morning
that I got the sequence.
RADIO PRESENTER: It's six o'clock on Saturday the 11th of January
and with the latest BBC News...
Got up the next morning and just sat in my bedroom in front
of my computer, basically huddled over it in my PJs,
designing the vaccine.
Dr Teresa, or Tess Lambe, works at Oxford University in one
of the world's pre-eminent centres for vaccine development,
the Jenner Institute.
It's named after Edward Jenner,
who pioneered the world's first vaccine, over 200 years ago.
Vaccines have worked the same way ever since.
The vaccines trick your body into thinking you have an infection.
So you want a vaccine somewhat to mimic,
to copy a natural infection.
Understanding what's causing the infection
is essential for vaccine design.
Each coronavirus particle is filled
with genetic instructions called RNA
and covered in crown-like spikes made of protein.
Inhale one of these viruses
and the spikes latch onto cells in our airways.
The spikes then change shape,
fusing the virus and the cell together.
At this point, the invading virus can replicate - fast.
The spike on these viruses is critical for vaccine scientists,
because its unique shape is key to the body's immune response.
Typically, when we're making an immune response,
we'll want antibodies,
and the types of antibodies you want
are known as neutralising antibodies.
Antibodies are like the defensive part of your immune system.
Neutralising antibodies block the coronavirus,
to prevent it from invading cells.
These antibodies are shaped so they bind tightly
to the spike protein.
When people are infected, their blood becomes filled
with these antibodies, to fight off the virus, which also helps
protect them from being infected again.
They're almost like a trained army,
so when they see a real virus,
they're ready to spring, they're ready to fight,
they're ready to clear a real infection.
In January 2020,
there were four main types of vaccine in development.
Oxford's is what's known as a viral vector -
a vaccine they'd already made in preparation
for just this kind of new threat.
All they needed was the genetic sequence from China.
What our vaccine is, it's a common cold virus.
We've crippled it, so we've knocked the legs off it,
it doesn't replicate,
and what we've done is we've then taken a small, tiny part
of the new coronavirus and we've put that into a common cold virus.
That tiny part is the coronavirus spike gene,
which the Oxford vaccine seeks to smuggle into the body
inside a common cold virus.
It is this genetic code that enables our cells to make the spike protein.
Which the body then recognises as foreign,
triggering an antibody response.
What your body sees is this small part of the new coronavirus
and mounts a strong immune response to it.
After design, the vaccine must be tested
to ensure it's safe and effective,
first in animals, and then in three phases of human trials.
These start small, but eventually involve tens of thousands of people.
For a normal vaccine programme, you'll typically have me say
that it takes up to ten years.
We didn't have that time.
So while we were designing the vaccine,
we were already talking to people about doing the preclinical work
and we were already planning for phase one.
We're working with people in Montana and also in Australia,
so a lot of late nights, a lot of early mornings,
a bit of insomnia and a lot of hard work.
It wasn't really a choice.
This is what I do - I have to do it.
In Brisbane, Australia, a molecular virologist
was also quick off the mark.
Hey, Millie, will you feed the chooks, please, sweetheart?
She's all grown up. She can do it herself.
Dr Keith Chappell of the University of Queensland
was just one year into a new vaccine research project
when Covid-19 struck.
While Oxford's vaccine is a viral vector containing the spike gene,
Keith's vaccine is composed of the spike protein itself.
Protein vaccines are the vaccine that's tried and true.
You know, hep B vaccine is protein,
some flu vaccines, so proteins are...
..the vaccines that have been shown to work.
It really is the most simple type of vaccine.
It's just a small component of the virus
and it's combined with a chemical called an adjuvant,
which says to your body, "Look out.
"This is what is potentially a nasty pathogen.
"Make an immune response to that."
Using the coronavirus spike protein as a vaccine
presents Keith's team with a key challenge.
It's a very big day.
A spike protein is highly flexible,
it wants to fall apart,
it wants to flip into other structures.
What we've got is the molecular clamp.
It's like a bulldog clip that holds it together
and allows it to stay 100% in that structure
that's present on the surface of the virus.
The shape of the coronavirus spike protein
before the virus meets our cells
is what triggers the most protective antibody response.
So Keith must make the spike protein in the lab,
locking it into exactly the same shape
by adding another protein that acts
a bit like a clamp.
And that protein is a tiny fragment of HIV.
The reason we chose this protein is because it's so well-understood,
it's a highly stable structure.
There is absolutely no risk from this type of vaccine,
there's nothing that makes HIV replicate.
There is only one small fragment of a protein
that is also present in HIV.
Then we hit go.
And it does it all for me and it makes all those cool "woo" sounds.
That's your robot.
Protein vaccines are a well-established technology,
so even a unique vaccine design like Keith's
can be cheaply and easily manufactured around the world.
Potentially vital for reaching developing countries.
We've got a key core team, which is Julia, Selorm, Danushka,
specifically employed for vaccine development.
They have, you know, the real focus and drive to, you know, put
in the hours and work together.
My father-in-law passed on because of the pandemic,
so for me and my family, it would be good news to know
that the vaccine that UQ is developing
proved to be successful.
Coming from Africa, I'm very much aware of infectious disease
that affects so many people,
so trying to develop vaccines has always been a passion for me.
And the loss of this loved one even made it more important.
Let's get this colony PCR on
and then have to start splitting the CHO cells.
When you're working on this thing, you see the amount
of effort that the team is putting in.
You want to succeed,
you want to be the ones that get a vaccine out there.
Making the only Australian vaccine
put Keith in the spotlight.
Yeah, I'm a star.
HE CHUCKLES Good luck. Thanks, mate.
Yeah, our status around the university has kind of skyrocketed
with all the notoriety and everything.
So, yeah, it's been interesting to go from just being one
of the new academics, I guess, to right in the limelight.
Probably the most important project in the university.
You're a superstar now, aren't you? That's me.
The cameras following you.
NEWSREADER: Coronavirus is now spreading at a faster rate
around the world than in China, says the World Health Organization.
Almost 40 countries are affected.
KETTLE WHISTLES
TRANSLATION:
George Gao is China's chief scientist
in charge of tackling Covid-19.
A veteran of fighting bird flu and SARS,
he favoured a traditional approach to vaccine development.
To create an inactivated virus vaccine,
the Chinese team take the coronavirus
and treat it with a chemical to damage its genome
and stop it replicating,
while leaving the surface structures of the virus,
including the spike, intact.
Injecting this inactivated virus into the body should trigger
a strong antibody response.
Not just antibodies against the spike,
but also other antibodies against the rest of the virus.
If it works, this should offer good protection from future infection.
In a high-level bio-safety facility, Gao's team first had to grow
a large quantity of the deadly virus.
George Gao's chief cook is Professor Wu Guizhen,
responsible for bio-safety at Chinese CDC.
It was Wu's task to grow the virus samples
that would become the seed stock
for China's inactivated coronavirus vaccines.
Wu had to choose a stock of coronavirus
that most closely matched the dominant strain
infecting people in early 2020,
because the closer the match, the better the immune protection.
While inactivated vaccines like China's have been used for decades,
an entirely new method was chosen by a big pharma giant in America.
Pfizer's vast research and development centre
is in Pearl River, New York.
Over the years, we have a huge portfolio of vaccine
addressing all kinds of infectious diseases.
I mean, we are talking hundreds
and hundreds of millions of doses
of vaccines that are being produced every year.
All right. Jess, I didn't take my iPhone.
I have no idea what I have to do.
Dr Kathrin Jansen leads a team of 650 people
as Pfizer's Head of Vaccine Research and Development.
Smuggled out of East Germany at just two years old,
her family started life in the West with just the clothes
on their backs.
I had whooping cough as a child,
and, you know, you get a medication that stops your cough.
That is impressive.
And so I thought that would be wonderful, to work in a field
where you could develop, you know, those little pills that would make
people feel better.
Kathrin teamed up with a long-time collaborator
from a small German biotech company - Dr Ugur Sahin.
TRANSLATION:
I said immediately, "Yes, we'd better get going on this."
So we started the work together
before the official contracts were signed.
BioNTech and Pfizer's vaccine takes a ground-breaking new approach never
before licensed for use in humans, called messenger, or mRNA.
Instead of smuggling the spike gene
into the body inside another virus,
like Oxford's viral vector...
..Pfizer first make a copy of the spike gene in the lab,
made from a type of genetic code called mRNA.
And then deliver this into the body
in a protective bubble of fat, or lipid.
Once inside a cell, the bubble breaks down
and the coronavirus spike is built.
Again, triggering those all-important antibodies.
The vaccine approaches that we had lots of experience with,
we rejected all of them.
The attractiveness of the RNA platform
is that it allows you to adapt very quickly,
you can go really at light speed.
The only cons in people's mind is that there has never
been a vaccine produced on the RNA platform,
so it was, I guess, a fear of the unknown.
Pfizer, one of the largest companies in the world,
tested not one, but four different versions of BioNTech's mRNA vaccine.
This huge infrastructure that was tested and proven
was at our fingertips, with really unlimited resources,
so we didn't have to worry about money,
we didn't have to worry about, you know,
is this approach a little cheaper than that approach?
All of those considerations were gone.
Another mRNA vaccine, was also being developed
at America's National Institutes of Health.
And in early 2020, as the virus spread,
the US top biomedical research centre
was already several steps ahead.
I didn't know if we could beat it or not, but we felt we had a way
forward because of our experience of other respiratory viruses.
Dr Barney Graham is Deputy Director of the Vaccine Research Centre
at the NIH.
For decades, he's developed new vaccines for emerging diseases,
most recently against another coronavirus, called MERS.
By the end of 2019, we had already made
a MERS coronavirus spike protein that was stabilised,
delivered by mRNA and protected mice.
We felt like we had a way of doing this,
and so we wanted to go just as fast as we could.
Using the method they'd honed with MERS,
within weeks, Barney's team had an mRNA vaccine
against the new coronavirus,
first testing it on mice, then on monkeys,
to see if it induced a strong antibody response.
This work was led by NIH Lead on coronavirus vaccines
34-year-old Dr Kizzmekia - or Kizzy - Corbett.
We did this so fast because we did everything
for the last six or seven years, very slow.
Why wouldn't you use all of that knowledge that you prepared
to really deploy a vaccine as quickly as possible
in this moment?
Hi!
Kizzy first came to NIH 15 years ago,
as a teenage summer intern in Barney's lab,
encouraged by family to follow her passion for science.
You did such a wonderful job. I just loved to hear your speech.
Thank you.
Ironically enough, I was interested in coronaviruses
because most other people were not.
You want to build a niche, and so you want to tap
in to some uncharted territory,
and the pandemic came and all of that changed, for sure.
REPORTER: The World Health Organization is expressing
new concerns about the spread of the virus,
as more cases begin to pop up outside of China.
REPORTER: The President and the Coronavirus Task Force meeting with
the vaccine makers, the President trying to get a sense of timelines.
In early March, the NIH vaccine was already just days away
from the first human trials.
It's because of the new technologies that have been developed here.
The new vaccine would be manufactured
by NIH's pharmaceutical partner.
We had this beautiful, productive collaboration
with this biotech company - Moderna -
and they knew how to make vaccine really fast.
And just 66 days after George Gao sent out the virus sequence,
the NIH Moderna vaccine became the very first shot against Covid-19
to be trialled in humans.
In Seattle, science writer Ian Haydon was one of 120 volunteers
for this first phase-one human trial.
REPORTER: Well, a glimmer of hope in the fight against the coronavirus
with the first US trial of a vaccine now under way.
It is Wednesday morning
and I'm on my way to receive my first injection.
Phase-one clinical trials answer the simple question -
is this vaccine safe for a human being?
Is it going to hurt? Have you had flu shots before?
Yeah.
Shouldn't be any worse than that.
The secondary point of them is to, oftentimes, to find a dose
that is suitable and safe, but also elicits
really good immune responses.
Ian received the highest dose being tested.
And then a Band-Aid's going to go on that.
That was not bad. Good.
So, a little over 24 hours ago, I got my first injection
and I'm feeling fine.
I have no symptoms other than an arm that's getting pretty sore.
Volunteers are monitored closely as vaccines must reach nothing less
than the highest standards of safety.
If you're planning to immunise seven billion people on Earth
who are otherwise healthy,
you need to make sure what you're giving them
is not going to cause any long-term problems.
28 days after his first vaccination, Ian returned for a booster.
By ten in the evening, I started getting chills all of a sudden.
I was shivering a little bit.
But I ended up falling asleep.
I woke up, though, in the middle of the night with a pretty high fever
and nauseous, and with a pretty bad headache.
Basically, all the stuff that I had been told to look out for.
We got to urgent care at about five in the morning
and the lead doctor on the vaccine study
was already there waiting for us.
I spent a lot of time just alone on the bed,
unsure of what was happening to me.
It was scary, it was scary not knowing.
Some side effects can indicate that your immune system
is really kicking in, but we have to carefully monitor them
to make sure that the adverse reactions are not worse
than the disease you're trying to protect against.
And that's why we start small and we start slow
and we look at the safety profiles.
Ian's symptoms were the most extreme of any volunteer
in Moderna's phase-one trial.
But two days later, he was fully recovered.
Having worked out the right vaccine dose - much lower than Ian's -
the scientists could move towards phase-two and three trials,
testing it on hundreds and then thousands of people.
But by the time Oxford, Pfizer and the Chinese CDC
also had phase-one human trials under way,
cases were surging exponentially.
REPORTER: A virus that knows no borders is taking a worldwide effort
to confront it.
It was absolutely terrifying, seeing graves being dug.
You know, we needed to do all we could, and that's how every
single person working on vaccines felt - I can guarantee that.
I did look at the dashboards in the early days,
but as it became apparent how this was going,
I didn't do a daily check
because that can incapacitate you, that can slow you down,
that can put too much of a burden on you.
We knew what we had to do and we just had to get on with it.
With hopes pinned on vaccines,
by the end of May, there were over 120 teams in the race,
many now with massive government support
totalling billions of dollars,
alongside new partnerships with big pharma.
Queensland got the backing of global biotech leader CSL
as other protein vaccines also made progress.
Oxford advanced with partner AstraZeneca on their viral vector,
while other vector vaccines gained ground in America and Russia.
The Chinese CDC paired with pharmaceutical companies Sinopharm
and Sinovac to scale-up production.
And the mRNA vaccines surged ahead.
Usually, mass manufacturing would never begin
until all three phases of vaccine testing are complete
and a vaccine is known to be safe and effective.
But by mid 2020, factories around the world were already
preparing to churn out doses on an unprecedented scale.
There are seven-plus billion people in the world
and there is going to be a race to vaccinate everybody.
We're going to need billions of doses.
We really need more than one manufacturer to be successful here,
because we have a big task immunising the entire world.
Kalamazoo, Michigan is home to Pfizer's largest manufacturing site.
Here, Pat McEvoy directs Covid vaccine production.
I've been involved in a lot of projects, but nothing to this scale.
It's unprecedented.
This hallway's a little over a-quarter-of-a-mile long.
This facility had to gear-up to manufacture billions of doses
of a vaccine they'd never made before.
The operation, here and across Pfizer's entire manufacturing
and distribution network, is coordinated from home
by Pat's boss Mike McDermott.
And they're both looking to run through the weekend, I guess.
MAN, ON PHONE: Oh, yeah, 24/7.
Manufacturing will typically take three to five years to start
from scratch and build the facilities and get them approved
by the agencies around the world.
So the notion of actually designing, building and have it running
and shipping in nine months seemed ridiculous to me.
Pfizer purchased $300 million worth of raw materials to be ready to make
any of the four mRNA vaccines being tested.
Though they had no idea if any would work,
they also had to rapidly expand production capacity.
You're looking into our newest aseptic line.
It is a restricted-access barrier line.
It's 100% dedicated to the Covid vaccine.
The company gave us all the resources we needed,
so it was a blank cheque.
Anything we could imagine, anything that we could think of, we just did,
and that gave us a lot of speed.
This is the automated visual inspection.
So there's 15 cameras that are taking dozens of pictures
as the vials come through, and they're looking for any defects.
Once their mRNA vaccine is made, filled into sterile vials
and checked, the final step is storage.
And while inactivated protein and viral vector vaccines
are chemically very stable, mRNA vaccines are not.
mRNA can break down very quickly,
unless kept incredibly pure and very cold.
As wonderful as the mRNA technology is, it wants to degrade,
so what we do is that we freeze that mRNA
after it's made at minus 80 and it stabilises it,
keeps it nice and quiet, so it doesn't degrade.
Every two weeks, we'll bring in three truckloads,
each containing 20 freezers.
We currently have 200 freezers on site,
another 60 showing up today.
This facility was built solely
for the storage of millions of doses of the vaccine.
These freezers eject off an immense amount of energy,
so we put in six air handling units
just to remove the heat load coming off of these freezers.
With Pfizer's vaccine trials still in their early stages,
this was a huge gamble.
My team spent about a half a billion dollars before we had any idea
if the product was going to be successful.
That's more than unusual. That's crazy.
With a big pharma partner in place and the Australian government
pouring funds into Queensland's protein vaccine,
Keith was working round the clock as his phase-one trials
also moved ahead.
30 seconds.
Keith, how you going? Yeah, good, thanks. Good to see you.
Two, one, when you're ready.
All right, going in now.
120 volunteers were randomly assigned
to groups that received either a placebo
or a low, medium or high-dose shot of the Queensland vaccine.
Everyone returning a few weeks later for a booster.
Hi. You must be Joel. You know, we really appreciate you being here
and go through this for us. Appreciate you inventing it.
THEY LAUGH
What we're excited to see is the immune response.
So, that's why we have you coming back every couple of weeks,
and taking blood. So we'll be analysing that
to see how it works against the virus.
Their rapid progress made the Queensland team headline news.
HE LAUGHS
How do you feel about that?
THEY LAUGH
That's all right. I liked that movie when I was a kid.
Yeah, everyone loved that movie.
While Keith's team juggled plans for mass trials and manufacturing,
just weeks into their phase-one trial, initial antibody data landed.
News just in.
The 5 microgram and the 15 microgram doses
are identical in the level of immune response,
so that is really good news. Yes.
The new results, which are the ones that I've been hanging out for,
the immune response data,
mid dose and low dose are pretty much comparable.
And a single dose at the lowest dose we use
gives an immune response around the same level as exposure to the virus.
That's fantastic news for us. That's what we want to see.
So, after we give these participants their second dose, likely the vast
majority of the participants will have an immune response
that is higher and likely more protective
than being exposed to the virus. So that's absolutely phenomenal.
There's a lot of work to do, but we're on the way.
Ooh, got him.
For the team, we are feeling on a high, but, you know,
I am literally exhausted.
I haven't had a good night's sleep for...
..I don't know when.
Vaccine development has never been done at this speed before.
What keeps you up at night is, have I made a mistake?
What will we miss and get wrong
that will cost us a week and will cost lives?
You know, it's just constantly running through your head.
By late July, the frontrunner vaccine teams began publishing
results from their phase-one human trials in the world's
leading science journals.
NEWSREADER: The biotech company Moderna reporting some
promising results today.
The new data from the company's phase-one trial shows the drug
appears to be safe and triggers a robust immune response.
A team of scientists at Oxford University say the vaccine
they're developing appears to be safe and triggers
an immune response.
..Early results published in The Lancet, and so far, so good.
That's the first big outcome. You know, is the vaccine safe?
Is it immunogenic? And I think at that point, collectively,
everybody just went, "Whew, OK, that's box one ticked."
Prof Katie Ewer works alongside fellow immunologist Tess Lambe
at the heart of the Oxford lab.
And while Tess is focus is antibody data,
Katie is the undisputed expert on T cells.
Most vaccines that are available today work by inducing antibodies.
But for some diseases, antibodies on their own aren't enough -
we need T cells as well.
If antibodies are the immune system's defensive weapon,
T cells are trained to attack.
Once exposed to the virus, they become precision hunter killers,
ready to stem viral replication by seeking and killing off
infected cells.
For Katie and her team, the success of the Oxford vaccine
could depend on whether it stimulates a strong T cell response.
We have to co-ordinate ourselves, so we're not all trying to use
the same things at the same time.
So, that's that for another hour.
Each week, they have to analyse hundreds of samples
from trial participants.
When we take the blood sample from one of our vaccinated volunteers,
we do a particular test on it called the ELISpot.
The ELISpot test counts the number of T cells that recognise
and attack the virus one by one.
So, we're going to mix those T cells in an ELISpot plate
with some small pieces of the protein of the virus.
If those T cells are able to make a response to the virus,
we'll be able to see small spots in the bottom of the well.
And each one of those spots is the footprint of a T cell
that can recognise the virus and fight it off.
After leaving the cells to respond overnight,
the results.
Go back.
Nice and crisp.
Yeah, they look good. And these are which group? 8?
These are 8B. Nice.
Just the fact that there are T cells that can recognise the virus there,
you know, it's another little milestone, that, yes,
everything's working.
One of the things about this trial is that we just process so many
more samples and run so many more ELISpots than we would ever do
on any other trial. And when you know everybody's
exhausted, and everybody's worked loads of weekends,
and I just hate being that person who has to go in and ask everybody
again to just give a bit more and try a bit harder
and go a bit further, when everybody has already done so much
and is already so exhausted.
REPORTER: What would normally take years has been done in three months
by scientists at Oxford University.
Rarely has a medical trial had so much riding on it
for so many people.
There's just so much pressure to get everything right.
Come on.
When you're there all day, it's really nice to have
that separation and get a bit of daylight.
You know, make sure I've sort of got that space to switch modes,
if you like, from scientist into family
and not be still in my work head.
What did you get up to today?
It's been hard not seeing the kids as much as I'm used to seeing them,
and there have been times when they've been like, "When are you going to be at home?"
You know, and that's been quite difficult.
What did you get up to? Xbox?
Aha.
Minecraft, or...
I haven't seen my parents since the beginning of lockdown,
cos my mum was vulnerable,
so she was shielding and then
she became really unwell.
Just around the time that The Lancet paper was coming together
and everything was being finalised,
she was rushed into hospital
and passed away within a day or two,
which was just...
It's awful at the best of times,
but having not seen her for so long
and her missing the sort of...
..the kind of, the first big milestone for the trial
of the paper coming out, you know,
I was really disappointed about that because she would
have been really happy to have seen that.
And so that has been really difficult to cope with
on top of the workload and, you know,
on top of everything else, but...
Yeah.
BBC NEWS: In the last 24 hours,
Brazil has reached two million cases,
India, one million.
And yesterday saw the highest daily total of new infections
in the US - over 73,000.
It's devastating to see that we can't seem to
get this pandemic under control.
What keeps me sane is walking in the park in the morning
and listening to the birds sing.
Walking helps me to
get out of the thinking mode of,
you know, my work
and really clear my mind.
At almost exactly the same time as Moderna and Oxford,
BioNTech and Pfizer also released
positive, early human trial results
and Kathrin Jansen selected one of their four MRNA vaccine designs
to take to the next stage.
We saw data on one candidate
that looked good.
The candidate they selected looks even better in terms of the antibody levels
and the T cell levels,
but that it is more tolerable.
I thought it was pretty spectacular, though,
to see those data.
But then again, you know,
I cannot be too elated
because the biggest...the biggest hurdle now that we have to overcome
is to demonstrate in a very large
phase-three clinical study.
We now have to do the hard part.
Does it work?
And if it works, how well does it work?
Pfizer now moved to phase-three trials,
involving tens of thousands of people.
Usually, after early trials
with just a handful of volunteers,
the next step would be phase two with a few hundred.
But given the urgency, these larger trials happened all at once.
The care for the quality,
looking carefully at safety,
all of this was what I call normal routine procedure.
The process never changed.
It's how we compress time
and how we did parallel work.
That's really what changed.
To recruit the huge numbers needed,
Pfizer had 150 phase-three trial sites
across five continents,
and New York City was home to one of the largest,
with 280 volunteers.
At Mount Sinai Hospital
Judy Aberg was the lead trial doctor.
It looks like in some parts of New York it could be up to 6%.
I mean, this is just like starting all over again.
Do you see it? Yeah, definitely.
You know, I will say that all the participants are really hopeful
that this will be the vaccine that works.
In any phase-three trial
the participants are divided into two groups.
One group are given a vaccine,
the other a placebo.
It's a busy morning.
We have 11 people coming back for their second vaccine
and then we have several people coming in now
for their initial consent
and then they too would get vaccinated.
It takes 45 minutes to thaw and prepare each dose,
making sure to hide any clue what's inside.
This is vital because the trial is blind.
Neither doctors nor volunteers know who is in which group,
to ensure no risk of bias.
Even if they're preparing placebo, they have to take that 45 minutes
of time so that we remain blinded to what's going on.
All the way down and then to the right.
What we don't want is people assuming that they actually
got the vaccine and that it works, so that they let their guard
down because they believe they're protected.
We absolutely do not know
if this vaccine is protective at this time.
So that's very critical that people understand this.
The only way to discover if the vaccine really does work
is to see how many of the vaccinated volunteers fall sick with Covid-19
compared to those in the placebo group.
And that takes time.
We need to register a million more volunteers.
The vaccine trial needs Americans of every race, location and medical condition
to help in one of the most important endeavours of our lifetime.
Recruiting thousands of volunteers on this scale and at this speed
had never been attempted before.
And in September, Moderna, who began their phase-three trial on exactly
the same day as Pfizer, revealed they'd hit a problem.
40 of 45 participants in the NIH Moderna phase-one trial were white.
Lack of trust, especially in communities of colour,
is not without good reason.
The shameful Tuskegee experiments
occurred within many of our lifetimes.
In the 1930s, government doctors conducted experiments
on black men, leaving them untreated for syphilis.
I was not surprised that there was hesitancy around enrolling
in clinical trials from African-American people.
The hesitancy comes from a history of medical injustice
that fuelled mistrust - that is just undeniable.
..Ideas that are going to contribute to their scientific output.
Given Moderna's initial failure to recruit from diverse communities,
Kizzy increasingly spent time speaking out.
The one thing that's important around vaccine hesitancy,
black people actually have never been asked...
When trust is stripped from people,
rebuilding it is brick by brick, right?
You know, you have to really speak to targeted audiences
and you have to speak with a voice that people do trust,
and from a perspective that they understand.
It's telling about the way that we think about science.
Dr Graham said to me
that for every 1,000 people
that we inform well enough that they choose to get vaccinated,
that's ten lives that are saved.
And when you're on a webinar with sometimes 10,000 people,
the numbers add up, and there's a big impact.
You either do it or people die.
The death rate.
Crazy.
Scared the hell out of me.
In Boston, 60-year-old Anthony Shivers was all too aware
of the fears that surround the virus and the vaccine.
I got to find something.
I'm going through my phone, I'm on Facebook, and I see people say,
"Don't take the shot, because the shot will kill you."
Imagine that? When I hear things like this coming from black people,
that really concerns me, because this is a disease.
This is not a me disease. This is a we disease.
This is a disease that affects everybody.
You understand what I'm saying?
Despite the urgent need for a vaccine, Moderna deliberately
slowed down their phase-three trial to focus on only recruiting
people of colour.
I had heard that they needed blacks
to get involved with the Moderna trials,
and a lot of blacks weren't signing up.
In order to solve a problem,
you've got to be a part of the solution.
So I went to the hospital and I got my first shot.
I got a call from my sister telling me she was concerned about me taking the shot.
After a month of calling and me feeling good,
now she wants to take a shot.
Her husband's going to take the shot.
I got other friends taking the shot, so I'm really happy about it.
Look at me.
You know, ain't nothing wrong with me!
HE LAUGHS
For Kizzy, building trust in vaccines is every bit as important
as developing them.
I have the ability to talk to an Anthony Fauci or a President.
And then also I have explained the vaccine to my cousin,
who's in prison, who I talk to very often,
and he gets it, too.
I'm happy to be a connection to people,
to this extremely confusing system
of how vaccines are made and how are vaccines
approved and how the trials work.
Representing, like, my community in that way,
my purpose of resonating with my community is a big deal for me.
At around the same time that Moderna had to pause recruitment,
there was breaking news from Oxford.
BBC NEWS: A major trial of a coronavirus vaccine
developed by Oxford University and AstraZeneca
has been temporarily halted worldwide,
after a volunteer taking part in the UK fell ill and was admitted to hospital.
Pausing and stopping and holding rules get triggered all the time.
This is normal.
This is what happens in clinical trials.
The trial was paused because of what's called an adverse event.
As soon as a participant's admitted to hospital,
we have to look and see, were they hit by a bus?
Did they break their leg skiing?
Or is there something else that we need to look at more closely?
I think people should be reassured the trial pauses if something like
that happens, because if it didn't, that would be more concerning.
During mass trials,
it's inevitable that some people will be hospitalised or perhaps even
die for reasons unrelated to the vaccine.
But every instance must be investigated.
What was unusual was the glare of the world's media.
We didn't expect... Well, certainly I didn't expect for this type
of normal activity, when you're following up individuals
so carefully, to have such a big impact around the world
and to make... To make headline news.
In this single case,
a link between the volunteer's illness and the vaccine
could not be ruled out,
but given the minuscule risk,
the Oxford trial was deemed safe to continue.
But the pause set Oxford's progress back.
And Moderna's delay to recruit more people of colour,
meant BioNTech and Pfizer now seemed best placed in the race
to get phase-three results first.
So this race is just kicking off in the pivotal trial.
Meanwhile, just a bit behind, Queensland's vaccine was preparing
to embark on its mass phase-three trial.
The Australian government made a billion-dollar deal
to buy 51 million doses of the Queensland vaccine -
enough to fully vaccinate the entire population.
But then, one night in October, some unexpected news.
We thought our vaccine was looking perfect.
We've got good efficacy data from animals.
We've got manufacture.
The safety is looking fantastic.
And now we've got a problem that we need to work through.
This is a HIV diagnostic that a participant who's
received our vaccine - what we're looking for here is this band
that's showing up very faint there, that would be considered
a positive or a false positive.
We've got this other version here from a different company,
and this version shows up negative.
The problem related to the molecular clamp in Keith's vaccine,
built from a tiny fragment of HIV protein.
The trial revealed that some participants not only test positive
for antibodies against the spike protein,
but also for antibodies to HIV.
So what we did this week was we purchased
a range of diagnostics that we could get our hands on.
The volunteers had not been infected with HIV,
but false positive HIV results
in some diagnostic tests are a big problem.
You know, I don't think it's a deal-breaker for us.
We can find a way around.
We just need to work it out.
In China, George Gao and Wu Guizhen faced a different kind of problem.
Their vaccine progress slowed
because there was so little Covid in China.
Having crushed local outbreaks so effectively,
China's greatest threat was now from the virus raging elsewhere.
At Beijing Capital International Airport, China's CDC
conducting strict screenings for international arrivals.
A vaccine was still desperately needed, but they had no way
to test it at home.
The team pivoted, setting up phase-three trials in countries
around the world with high Covid levels, and for Wu,
there was pressure from the authorities to deliver results
as quickly as possible.
By autumn 2020, impatience for a vaccine was growing.
BORIS JOHNSON: We don't yet have a vaccine, unfortunately.
You know, you really feel that they must be on the verge of it.
NEWS: Until they succeed, the Government will consider tighter restrictions on everyone.
On the one hand, you've got all these people saying,
"Oh, we don't want a vaccine that's been rushed."
At the same time as everyone saying, "We need a vaccine and we need it tomorrow."
You know, that's really challenging when you're just under a massive
workload because you don't know what's coming next.
As England went into its second national lockdown
and the US election approached,
international pressure intensified.
DONALD TRUMP: Moderna is doing very well.
Pfizer is doing very well.
The vaccine will be delivered very soon.
Could even have it during the month of October.
Politics should stay out of science.
So it is the science, at the end of the day, that you want to follow.
There was a lot of political pressure on the vaccine
manufacturers to do things faster.
This is a distraction.
It's not helpful.
And you block it out and you just focus on the task.
In phase-three trials, even the scientists don't know
when results will come.
Each trial must continue until a predetermined number
of volunteers test positive for Covid-19.
Independent statisticians monitor those cases in real time.
Only when the threshold is reached, do the vaccine scientists discover
whether those who caught Covid had the vaccine or the placebo.
It's this comparison which reveals efficacy -
how well the vaccine works to prevent disease.
Now it's what I always say, my least favourite game.
It's a waiting game.
I think that part of my anxiety management has really helped me
to see things for what I can control versus what I cannot.
So, preclinical data, I could control it.
So there's so much anxiety around that.
But when you give 30,000 people a vaccine or a placebo
and then allow them to go out into the world, you're really asking
the world to give you the answer.
There's really nothing you can do at that point.
When you're working through problems and you're working hard
and you're moving with your team and everybody is pulling in the same
direction, you don't think about this.
But all of a sudden in this moment of what will the results be,
you just feel powerless.
It's out of your hands.
And now this is the moment of truth.
And there's nothing you can do about it.
Then, less than ten months after the race for a vaccine began,
an answer.
And it was Kathrin who received the call
from Pfizer's CEO, Albert Bourla.
Albert called and he said, "Kathrin, I have to tell you,
"we are allowed to say that your vaccine
"is over 90% efficacious."
NEWS: This is indeed a momentous day. We've been waiting for these results...
News that a vaccine against coronavirus
has proved 90% effective.
I was just out of my mind, you know, just laughing
and dancing around there.
It is a great day for science.
It is a great day for humanity.
In their final analysis, of 170 volunteers who fell sick
with Covid-19 during the trial, nearly all, 95%,
were in the placebo group.
For the first time, a Covid-19 vaccine has been shown
to protect against the disease.
We're talking about, for the first time ever,
people outside of a clinical trial
receiving a coronavirus vaccine before Christmas.
So it's pretty, pretty incredible pace here.
This immense relief that, yes,
now we will fight this thing
and we will get the pandemic under control.
It's just like... It's an amazing feeling.
I mean, that's all I can say.
Just one week later, there were enough cases of Covid
in the 30,000-strong NIH Moderna trial to un-blind their data.
Well, good morning.
Good morning. Um... How's it going?
I am calling you because
we got results yesterday and they're going
to be announced in just a few minutes by press release.
OK!
What did they say?
Well, there was 95 cases total,
and 90 of them were in the placebo group.
Five were in the vaccinees.
Oh, that's...
Yeah, that's, uh...
That's exciting! So it looks like it's going to work,
at least for a while.
And of the 11 severe cases, all 11 were in the placebo group.
So none of the vaccinees had severe disease,
which is even better news.
That is... That is amazing news.
Wow.
I don't even know what to say.
NEWS BROADCAST: Breaking news for you.
Moderna has just released the first analysis
of its coronavirus vaccine and their vaccine is 94.5% effective.
This is huge. Our experts are being scrambled into position...
We expected it to work to some extent,
but to 90, 95%
efficacy for what was essentially a first in human vaccine
was astounding.
The relief that I felt was...
..overwhelming and...
..pleasing to the point that I just had to just sit in it
for a little while.
With the news this week of a potentially very effective
vaccine, countries are racing to prepare for a possible roll-out.
But Moderna and Pfizer's vaccines alone won't be sufficient
for the whole world.
This idea that no-one is safe until everyone is safe
is the founding principle of COVAX, the global scheme to ensure
distribution of vaccines to the most vulnerable worldwide.
COVAX invested more than $1 billion in several of the vaccines
in development, including nearly 400 million in Oxford-AstraZeneca's,
which can be transported in a fridge and costs just $3 a dose.
They also backed the protein vaccine being developed in Queensland.
But just a day after the Moderna triumph, the team behind COVAX
contacted Keith.
Just got off the call, got some news that really came
out of the blue.
Yeah, basically, we've just had our funding cut.
So, yeah, we're out of COVAX. All due to this HIV diagnostic problem.
Yeah, it's pretty devastating.
A lot of the people from our team are people that come from...
..Africa, Sri Lanka, countries that, you know, would be putting
their hand up for a COVAX-funded vaccine.
They wanted to be part
of giving something to the world, giving...giving back
to their communities and all of those communities.
You know, the vaccine is safe,
CSL has hundreds of millions of doses ready to go.
It's thermostable, so we can ship it everywhere in a fridge
rather than at -70, -80 degrees.
There's just... Yeah, there is the problem,
there is one problem, which is the diagnostics for HIV.
PHONE RINGING
OK, yeah. I'll be down in a second. Thanks.
Three weeks later, the Australian government also withdrew
their funding. Yeah, no, that's right.
The advice that we have received,
and the National Security Committee of Cabinet met this week and made
the final decision yesterday, is that the University of Queensland
vaccine will not be able to proceed, based on the scientific advice,
and that will no longer feature as part of Australia's vaccine plan.
With their place in the race over, Keith faced the world's media.
I hope that us being completely transparent and upfront
about these results boosts public confidence in vaccines, overall.
I think what we've achieved this year has been remarkable,
we can hold our heads high
and, you know, I think it's a very sad time, but also we're very proud
of what we have achieved.
Australia's quest for a home-grown vaccine is tonight over.
We have led the world in taming the virus, but in the battle
to beat it forever,
today, we were forced to concede defeat.
As a scientist, we have a lot of different jobs.
We have a job to make a vaccine, but we also have the job to train
people, to educate people and to be able to, I guess, step back
and say, "Look, we did all we could.
"There's these other vaccines that are also looking great,
"so take those."
You know, that's an important part of our job as well.
It's not all about making a vaccine and getting to the finish line.
In Oxford, Katie was still waiting.
It's Sunday night, 22nd of November.
I think we are about to find out the result.
You know, two of the other big vaccine manufacturers have released
their efficacy results and we've known that we were very close,
for some time now. I'm feeling excited about it.
But now that I know it's so close, I'm also feeling very anxious.
NEWS BROADCAST: The vaccine developed by scientists at Oxford
is set to transform the battle against coronavirus
around the world.
What we're measuring as Covid disease...
Come in. It's all right, we're just watching the press conference.
Different trial groups make the Oxford-AstraZeneca results
harder to interpret, but the average
efficacy is 70%. Not as good as the stellar 95%
from Pfizer and Moderna,
but it's another vaccine that works.
NEWS BROADCAST: This vaccine is highly effective,
it prevents people getting sick.
I feel relieved, a bit emotional.
I was really worried last night that we would just get a negative result
and everything that's happened for the last, you know, 11 months
would be, you know, for nothing.
So...no, it's good. It's good that we've got a result.
When we started on the process of developing vaccines,
the target was 50%.
I think if you'd put me in this seat 12 months ago and said,
"Would you be happy with a vaccine with 60% efficacy?"
I'd have been pretty chuffed with that.
And within the data for all three vaccines now over the line,
more good news.
These vaccines are stopping severe disease, they're stopping
you going into hospital. If a vaccine stops you from dying,
it's a vaccine I'd put in my arm.
We shouldn't keep concentrating on one vaccine
being better than another.
We should be happy that we have so many vaccines
because without a large number, we're never going to be able
to vaccinate the whole world.
We've put our backs into this and assuming that the regulators
give it the green light and that the Department of Health
can deploy it, really then, it's over to the public to determine
what impact it has. In order to get the levels of immunity
that we're going to need,
we need lots of people to go and get vaccinated
and I think they will and I hope they will, but that's when
I'll really feel like we've made a difference.
Hello!
We all want to go back to things more or less
how they were before, you know?
We all just want normality back, don't we?
Just nine days later, on December 2nd, that process began.
With vaccines packed and ready to go, the UK became the first
country in the world to approve Pfizer's vaccine for use
outside a clinical trial.
The race for a vaccine was now the race for vaccination.
90-year-old Margaret Keenan, well, she'll go down in history.
She's become the first person in the world to receive the Pfizer
vaccine against Covid-19.
ALL CHEER
And in the United States, just two days after the UK's V Day,
the FDA also issued Pfizer an emergency use licence.
My dad worked for NASA.
He was actually invited to Mission Control in Houston when the first
humans stepped foot on the moon.
I thought, I wonder if I'll ever experience that in my life,
that enormous upswelling of emotion and pride.
When I saw the truck being loaded, I was absolutely blown away.
So many people just cried with joy when our trucks moved away
from our factories.
In less than 24 hours, the first American will be given a dose
of Pfizer and BioNTech's coronavirus vaccine.
DONALD TRUMP: They said it couldn't be done,
but with today's announcement, we have now achieved that goal.
There is now hope that these grim days may well come to an end.
Following Pfizer, on January 4th 2021,
Oxford-AstraZeneca's vaccine was also
authorised in the UK.
TV: Vaccines bring hope but the roll-out
must happen quickly if they're to compete with the virus.
But that very same day, the country entered its third national lockdown.
So some good news with the AstraZeneca vaccine,
but all the figures are going in completely the wrong way.
Bit of a weird day. Obviously really happy to see the vaccine rolled out,
but really, really gutted that after the two lockdowns we've already had,
all the sacrifices that people have made - not seeing family,
not seeing friends, all the opportunities that have been missed,
the schooling that's been missed, not seeing everyone over Christmas -
and, you know, this is where we are, back again now,
it's just really gutting.
On the first anniversary of George Gao publishing the sequence
of the novel coronavirus, it was killing people
faster than ever.
WOMEN WAIL AND WEEP
The evidence suggests the vaccines work very well,
but when they don't get out fast enough, countries risk losing
control to deadly new waves of infection.
And this presents a huge opportunity for the virus.
By allowing it to get
to hundreds of millions of infected people,
the virus is going to find ways to evolve.
Every single person that's infected gives the virus
a new opportunity to mutate.
So we're fighting against an enemy that is constantly changing
and moving.
In the UK, Brazil, India, and here in South Africa -
all experiencing soaring infection rates in early 2021 -
the virus has mutated into so-called "variants of concern".
The variant of the virus identified in South Africa, for example,
is found to have mutations in the spike protein that subtly
change its shape.
Antibodies that neutralise the original strain of the virus
from Wuhan, that all vaccines so far are based on,
now don't seem to bind so well.
As long as the variants are allowed to expand and they become a concern
unchecked, then it just makes the job of the vaccine
so much more difficult, and I feel at the moment,
we're in a really dangerous position
between relaxing too much because we know we've got
the vaccines, but relaxing so much that actually we undo
all the good work we've done and we see a massive expansion
of mutant viruses that then render all of the vaccines ineffective.
I'm actually very concerned about this.
I'm worried about that
people get to too joyful and think that everything is OK now.
It is not yet OK.
If you're not careful and the virus is finding a way to escape immune
protection, we could as well start all over again.
And in South Africa, start over again is what happened.
South Africa has announced it temporarily is stopping
the roll-out of the Oxford-AstraZeneca vaccine.
This is after a study found that the vaccine was largely
ineffective against the new Covid-19 variant that was first identified
in South Africa.
Despite having a million doses of the Oxford-AstraZeneca vaccine,
in February, South Africa made a drastic decision.
It quickly obtained limited stocks of another viral vector vaccine,
made by Johnson & Johnson, which it hoped might work better
against the new variant.
One of the first recipients was the South African President.
Goodbye. How's the arm? The arm is still OK. Still OK.
Around the world, governments and scientists had to grapple
with the changing situation.
By March, tens of millions of people had received Chinese vaccines
in more than 25 countries, from China to Hungary, Indonesia to Zimbabwe,
even though phase-three trials were not yet finished, and the early
data on these vaccines was incomplete.
The WHO later approved the Sinopharm and Sinovac vaccines,
and China's unorthodox policy of speeding through roll-out
before trial results were finalised, seems to have been vindicated.
For all vaccine scientists,
it's about weighing the benefits against the risks.
If you can intervene with, let's say, a 40%-effective vaccine four
months before you can intervene with an 80%-effective vaccine,
you save more lives with the 40%-effective vaccine
that's delivered four months earlier.
And so being fast in an outbreak setting in some ways
is more important than being perfect.
Difficult decisions must be made everywhere. As in March and April,
when evidence mounted of extremely rare side-effects connected
to at least two of the viral vector vaccines.
NEWS: There is a possible link between the AstraZeneca vaccine
and very rare blood clots.
A small number of cases of serious blood clots in recipients led to use
of the Oxford-AstraZeneca and Johnson & Johnson vaccines
being halted or partially restricted
in several countries.
19 people have died.
That's out of 20 million who received the jab.
That's one rare clot in every 250,000 vaccinations.
For the vast majority of people, the risk of these clots
is far smaller than the risk from the virus.
For the world's vaccine scientists, the race against the virus
is far from over.
It's not as if we got the efficacy results and we've stopped working.
If anything, the work keeps going.
We're constantly looking at the new variants,
we're constantly measuring, assessing to see if we need
new vaccines, to see if we need new booster shots, to see
how long our immune response lasts.
Hey, guys. Has it come through yet?
Yeah, so that looks like a very good start.
Keith and his team are back at the bench, now targeting
the variants with an updated version of their protein vaccine,
this time with no HIV protein at all.
So, expression this week, purification next week. Yes.
We'll give it another shot.
And if new vaccines are required, the pioneers of mRNA
believe their triumph can be repeated.
The Covid-19 pandemic has exacted
and is still exacting
an unbearable human cost.
But thanks to the efforts of a small number of scientists,
we are now being protected against an even worse fate.
What's more, the way we do science is changed forever.
It's been a massive global collaborative effort whereby
everyone is invested in everyone else's success
from a vaccine perspective.
And so the sharing of knowledge in almost real time is unprecedented
in this moment.
We have transformed the way that vaccines are made, the way
that they're looked at and the impact the public
sees they make.
This is not really like anyone's life in science, I think, before.
You know, we've changed everything in the last
12 months in terms of, not just what we've done,
but what we've now shown is possible.
To go from a standing start with an unknown pathogen,
roll it out, you know, with phase one, phase two, phase-three trials,
emergency use approval, is an amazing achievement.
Hundreds of thousands of lives have already been saved.
As roll-out continues around the world, that number will become
tens of millions.
It's hoped that in time everyone will get their invitation
to the vaccination clinic.
CHEERING Viva soy!
When Kizzy and Barney got their call, it was to get
their own shot.
BEEP You're Barney Graham.
Yes, I am. Any questions regarding the vaccine?
No, I'm ready to go. All right.
How was that? Beautiful.
If you want to head to the observation area,
we'll keep an eye on you for 15 minutes.
Sometimes I just like to go over to the cafeteria
on the NIH campus, where a lot
of these vaccinations are done, and just sit there and watch
people be vaccinated.
It's, it's, it is really thrilling because it is such a relief
to a lot of people.
It is amazing to know that you contributed to that.
SHE SPEAKS IN OWN LANGUAGE