All language subtitles for NOVA.S50E17.The.Battle.to.Beat.Malaria.1080p.WEB.h264-BAE_track3_[eng]

♪ ♪

♪ ♪

NARRATOR:
This tiny creature
is at the center

of one of medical science's
greatest quests...

A battle to save
millions of lives

and end a scourge
that has shaped human history:

malaria.

One child dies every
single minute from malaria.

So you might ask yourself,
"Why are kids still dying?"

♪ ♪

NARRATOR:
For almost a century,

scientists have had one goal.

We don't want to use the word
"the Holy Grail,"

but if we got vaccines,

then, of course,
that would be transformational.

KATIE EWER:
The chances of success

are really, really small.

But the rewards, if you do it,
are enormous.

NARRATOR:
This is the inside story,
across four continents,

of a new vaccine against malaria

and the struggle to make it
succeed against the odds.

The field of malaria vaccine
research

is littered with failure.

ADRIAN HILL:
It didn't work,

it didn't work,
and it didn't work.

UMESH SHALIGRAM:
I remember very openly and
straight telling

that this is not going to work.

And after many
tweaks and changes,

it did.

Well, to me, it was unthinkable
before it happened.

♪ ♪

This could be a gamechanger.

You are touching human life.

You are going
to save the human life.

It's not one or two,
it's millions of lives.

Amazing.

NARRATOR:
"The Battle To Beat Malaria,"

right now, on "NOVA."

♪ ♪

ANNOUNCER:
Major funding for "NOVA" is
provided by the following:

♪ ♪

TIMOTHY WINEGARD:
Throughout our history,
the mosquito has been

the paramount killer
of humanity.

If we look at
our Neverland nightmares,

we're taught to fear

all these other creatures

because they kill so many
humans.

That's just simply not true.

For example, wolves and sharks

kill only about ten people
per year.

Whereas the mosquito,

this tiny little animal the size
and weight of a grape seed,

is responsible for up
to a million deaths a year.

But it's not
the mosquito itself.

It's the pathogens that hitch
a free ride

that cause so much suffering,
death, and destruction.

And of all the pathogens
that mosquitoes carry,

by far the most lethal and
the biggest killer of humanity

has been malaria.

♪ ♪

NARRATOR:
A highly effective vaccine
against malaria

would be
a historic breakthrough.

And getting there starts
with knowing your enemy.

London's Natural History Museum
is home

to one of the world's
greatest collections of insects.

Senior curator Erica McAlister

looks after 150,000 specimens,

representing
2,900 species of mosquito.

We have maybe 350 drawers
of mosquitoes,

but only 20 of those drawers
are the species

of mosquitoes that are important
for the transmission of malaria.

The difference between the males
and the females

is very important.

The males are all vegetarian,

but the female has to generate
the eggs.

Therefore, she needs a really,
really high-protein meal:

the blood.

We've got the proboscis,

her fantastically
long mouthparts.

It's composed of six stylets.

She uses two of those
to kind of,

like, penetrate the flesh,

she uses two of them
to keep it open,

and then her final two,
one is basically a tube,

which she will
suck up your blood with.

But the other one, through that,

she releases her saliva
to prevent the blood clotting.

And it is in that process
that the malaria parasite

is able to transfer into us.

♪ ♪

FILM NARRATOR:
Public enemy number one:
anopheles,

the malaria mosquito,
wanted for bringing

sickness and misery
to untold millions.

NARRATOR:
Today, malaria is considered
a tropical disease,

but until very recently,
it affected people worldwide.

And it's played a huge part
in our history.

WINEGARD:
The United States, for example,
was awash with malaria,

in particular across the South,

and even parts
of the Eastern seaboard.

♪ ♪

The American Revolution
was decided by malaria,

with the surrender of Cornwallis
at Yorktown.

He surrenders

because he only has 35%
of his troops left

on account of, the ague

is what the British
called malaria at the time.

Eight U.S. presidents
contracted malaria.

George Washington
was one of them.

He was bled, which was one

of the crazy cures at the time.
(girl crying)

He had his first bout at age 17,
and had repeat infection

throughout his life.

At the dawn of the 20th century,

a physician of tropical medicine
remarked

that the future of humanity
would be decided by one battle:

man versus mosquito.

FILM NARRATOR:
All right, men, now
we can begin to fight.

("Assembly" bugle call playing)

(clangs)

NARRATOR:
During World War II,

military casualties from malaria

were so high that the
authorities declared total war,

even recruiting Walt Disney
for the fight.

FILM NARRATOR:
Attaboy, Dopey,
kill her good and dead!

NARRATOR:
The newly invented insecticide
DDT

destroyed mosquito populations.

Swamps were drained.

Protection against bites
improved.

As did the availability
of malaria treatments

and tests.

WINEGARD:
In the Western world,

malaria was made extinct,
essentially.

America was declared
malaria-free in 1951.

As a result,
the malaria burden shifted

to the lower
socioeconomic countries,

specifically
in the global South.

Funding for malaria research
was drastically cut,

and malaria was generally
all but forgotten

in most wealthy nations.

♪ ♪

NARRATOR:
Nine out of ten people
in Tanzania,

East Africa, live in
the country's malaria zone.

♪ ♪

And it's the youngest children,

naturally much less able
to fight off infections,

who are most at risk.

Farhiya Salum is three years
old.

She lives in Kiwangwa village

with her mother, Zuhura Abasi,
a pineapple farmer

and small trader, and her
grandmother Huba Mohamedi.

ABASI (translated):
Farhiya has been sick
with malaria quite a few times.

She gets a really high fever.

Her whole body is so hot.

It gets particularly bad
at night.

It's so scary

that a single mosquito
can pass on malaria

and potentially kill someone.

MOHAMEDI (translated):
Growing up, we weren't aware
of malaria as a disease.

When I was ill,

I would be given roots and
herbs.

That's how it was back then.

Three of my children died.

I'm now left with six.

This is the area
where we buried my children.

On one occasion,
I went to the fields

with a healthy child.

A fever came on suddenly there.

And by the time we got home
and my mother attended to him,

he was gone.

Every time I come here,
it's so painful.

Malaria is such a bad disease.

Bad, so bad.

NARRATOR:
Across Tanzania
and much of Africa,

malaria costs
lives and livelihoods,

undermining the potential
of an entire continent.

Dr. Ally Olotu,
of the Ifakara Health Institute,

serves on the medical frontline.

(people talking in background)

OLOTU:
I got malaria when I was young,

and I also got malaria
when I went to the university.

That's when I became aware

that this is a,

it's an awful disease.

(people talking in background)

OLOTU:
Globally, malaria causes
over 200 million cases

and more than 600,000 deaths
annually.

About 80% of these deaths
are actually

young children
below the ages of five.

♪ ♪

OLOTU (speaking Swahili):

MAMA TAWAKAR:

OLOTU:

and was in grave danger
of falling into a coma

until he came to the hospital
just 24 hours ago.

OLOTU:

Seeing kids
who are suffering from malaria,

emotionally,
it's always difficult.

As a clinician, as a father,

I have to develop interventions

to do everything possible
to get rid of malaria.

(speaking Swahili):

NURSE:

OLOTU AND NURSE:

NARRATOR:
While Ally regularly treats
children who have been infected,

his colleague,

mosquito biologist
Fredros Okumu,

works on malaria prevention.

Hey, how are you doing?
How are the mosquitoes today?

Have you blood fed
the mosquitoes? Uh-huh.

To evaluate specific
products for protecting people,

we have to rear the mosquitoes
in our labs.

(mosquitoes buzzing)

We have to provide water,
sugar, and blood.

NARRATOR:
Today it is lab technician
Steward Ng'ala's turn

to feed the mosquitoes.

STEWARD NG'ALA (translated):
I don't need to be brave.

It's normal;
nothing to be afraid of.

It's not painful;
just a bit itchy.

♪ ♪

OKUMU:
The mosquitoes we have
in the lab are malaria-free.

It's something
that we scientists do, so...

I mean, I do it as well.

(mosquitoes buzzing)

(zipping)

NARRATOR:
Fredros uses these mosquitoes

to test insecticide-treated
bed nets.

It's estimated that over

the last 20 years,
tools like these have prevented

a staggering two billion
cases of malaria and nearly

12 million deaths.

Yes, there's been
extensive progress.

Is it sufficient progress? No.

Because now we have this
challenge since around 2015,

where there are many countries
in Africa

where malaria cases
are going up.

♪ ♪

There's not much killing
of mosquitoes.

So that particular net didn't
kill enough mosquitoes, okay.

The bed nets that we have
in the villages

are starting
to face a lot challenges.

Mosquitoes are no longer being
killed as effectively

because they have become
resistant

to the insecticides
that we put on the surface.

And so the bed net
can lose that quality,

the killing effect.

NARRATOR:
Despite concerns
about increasing resistance,

bed nets treated with
insecticide

remain the world's number one
weapon against malaria.

But research shows they reduce

child deaths by less
than 20 percent.

We need a transformational tool,

and I do not think there
is any medical intervention

that has done better
or more than vaccines.

♪ ♪

NARRATOR:
When it comes
to transforming human health

and saving lives,

vaccination is up there with
clean water and sanitation.

Smallpox,
which killed up to 500 million

in the 20th century alone,
was eradicated

in the 1970s
thanks to vaccination.

And there's also been
huge success against polio,

measles, and recently COVID-19.

But a highly effective malaria
vaccine has never emerged.

That's not for lack of trying.

Ally himself has worked

on multiple vaccine candidates.

OLOTU:
So do you know
what Daddy is working on?

What am I working on?

Malaria.
Malaria what?

Malaria vaccine.
Okay.

So that you can,

you can protect
children isn't it,

from getting malaria?

IRFAAN OLOTU:
Because children below,
under five years

who have malaria are in much
bigger danger than others.

And they die?
Yes, they can die.

But if you go to hospital fast,
you survive.

I saw a child, three years old,

who had malaria in the hospital.

But he was treated

and he will get better,
but he was very lucky.

As night falls, this
is the most vulnerable time.

That's when
the mosquitoes come in.

When the mosquito bites,
it inject into that child

small parasites.

We call them sporozoites.

These spend a very
few minutes in the blood.

And then quickly go and start
to multiply within the liver.

♪ ♪

And these kids
could be playing around.

They could be playing football,
they could be singing

with their parents.
(children laughing)

Nobody can suspect anything.

But from the liver,
within a few days

you could have thousands and
thousands of parasites

released into the blood.

They attack our red blood cells,
destroying them.

And this is what

actually give rise
to malaria symptoms.

That child you saw
playing with his friends

just a few days ago can
quickly become severely sick.

And if not diagnosed
and treated very fast,

that child might lose life.

NARRATOR:
It's this process,
the way the body is overwhelmed

before it has a chance
to fight back,

that makes malaria so dangerous,

and the development
of a vaccine so challenging.

We have developed vaccines
for other diseases, of course,

but most of these
are viruses and bacteria,

which are much simpler

pathogens compared to malaria.

It's a very complex parasite.

So I was really excited

to be part of the consortium
of scientists

put together
by the University of Oxford

to work on
a new malaria vaccine.

NARRATOR:
The University of Oxford

is home to one of
the world's largest academic

vaccine development programs.

In 2020,

the university's
Jenner Institute created

the Oxford AstraZeneca COVID-19
vaccine,

and since then,

three billion doses have
reached 170 countries.

♪ ♪

Adrian Hill and his colleagues
have found malaria

much more difficult.

HILL:
We've known for
over a hundred years

that it would be fantastic
to have a malaria vaccine.

People have been trying
for about 120 years,

ever since the parasite
was discovered.

I did a count about six months
ago of how many vaccines

had been made and gone

into clinical trials for
malaria,

how many different ones.

And that number was 142.

I'm not sure there's
another disease

where they've been that many
vaccines that didn't work.

(indistinct chatter)

KATIE EWER:
But don't you finish
at quarter past 12?

NARRATOR:
Katie Ewer is the lead
immunologist

on the Oxford team.

EWER:
I think malaria is more
personal for me

because it's children.

I think you'd have to be a very
hard-hearted person

not to be moved by a death toll
of 400,000 kids a year

dying in Africa, under
the age of five, from malaria.

It's a huge motivator

to work on something where

the chances of success
are really, really small.

But the rewards, if you do it,
are enormous.

♪ ♪

NARRATOR:
For the last 13 years,

the Oxford team has been working
on a vaccine called R21.

Its goal is to fire up
the body's immune defenses,

to be ready to attack the
parasite

at its most vulnerable moment;

just after it enters our blood.

When an infected female mosquito
takes a bite

and injects sporozoites,
malaria parasites,

there's about a half-hour
to two-hour window

before the parasites
invade the cells in your body

and set up infection there.

And that's the window
that we're trying to target

with our vaccine.

NARRATOR:
What the R21 vaccine must do

is mobilize an army of
antibodies.

The problem has been to produce
enough antibodies

to clear all of those parasites
very quickly.

When people are infected
with malaria,

they make antibodies
in the blood

that stick to the outside
of the parasite.

They're meant to stop it in
its tracks

before they can reach the liver.

But in a natural infection,

there just aren't enough
antibodies.

NARRATOR:
Threatened by just
a few invading parasites,

our antibody response
is usually too little, too late.

But luckily,
the malaria sporozoite

has an Achilles heel.

To invade the liver, it relies
on a coating called CSP,

the circumsporozoite protein.

HILL:
What we need are large amounts
of very specific antibodies

that bind as tightly as possible
to the circumsporozoite protein.

Then we should be able to stop
the parasites.

♪ ♪

NARRATOR:
This is where the R21 vaccine
comes in.

It is built from the CSP
protein,

and so induces the body
to produce an army of antibodies

tailor-made and ready
to neutralize the parasite.

But this is not a new idea.

First designed in 1987,

a vaccine called RTS,S already
does this.

I have had the privilege to work
on RTS,S malaria vaccine.

And the overall efficacy

of RTS,S is about 40 percent

against clinical disease.

40 percent may sound
as not very good efficacy,

but you have to think
about the burden of malaria.

We have well over 600,000 deaths
annually.

(cheers and applause)

NARRATOR:
After lengthy deliberations,
in 2022 RTS,S

became the first malaria
vaccine approved by the W.H.O.,

the World Health Organization,

35 years after
it was initially developed.

But RTS,S is expensive to
produce,

supply is currently limited,

and it falls
short of the W.H.O.'s

own target of having a
75 percent effective vaccine,

by 2030.

And so the Oxford team had long
set their sights on an upgrade.

R21 was born out
of the idea that perhaps

we could make a slightly
better version of RTS,S.

So it started with a PhD student
called Kat Collins

taking this on as her project.

♪ ♪

NARRATOR:
The RTS,S vaccine is made
of billions of tiny particles.

They're built
from a virus protein

that forms a harmless,
empty shell,

and part of the same CSP protein
that coats the malaria parasite.

Together, they trigger
the body's immune response,

but unlike the malaria parasite,

less than a quarter of each
particle's surface is CSP.

Kat Collins and
her Oxford colleagues wondered,

could increasing the amount
of CSP,

to better mimic the malaria
parasite, make a better vaccine?

We kept on trying different ways

to get that
to form into a particle.

And it didn't work, it didn't
work, and it didn't work.

And, eventually, after many
tweaks and changes,

it did.

That was a big day.

You can literally
see these particles

with an electron microscope.

And, boy,
those images are memorable.

And we thought, "Fantastic,
we immunized mice."

And guess what?

They were nearly
all protected very well.

This was 2012.

We were finally getting there.

And, of course,
getting there means you're ready

to try and manufacture
and go into the clinic.

♪ ♪

NARRATOR:
Oxford University's R21

was doing
exactly as they'd hoped,

creating a strong
protective immune response.

But that was just in mice.

The big challenge now
would be testing it in humans.

For this,
they called on Eleanor Berrie,

a specialist in vaccine
manufacture for human trials.

Vaccines are actually one
of the most

complicated things
you can manufacture.

But Adrian and Kat

were so enthusiastic about R21,

they had generated some
excellent pre-clinical data,

and that enthusiasm
rubs off on you.

So, you know, you begin to feel,
well, we could do this, yeah.

NARRATOR:
Eleanor and her team

only needed to make enough R21

to inject a small
number of healthy people.

Less than half a cup's worth,
but thousands of times

more than Adrian's team
had created

in the lab for their mouse
tests.

And this time,
with human safety on the line.

BERRIE:
We started the project in 2012,

and it took us
three-and-a-half years.

If we had been
in a commercial situation,

I would have think
that they would have

just stopped
the project on many occasions.

We kept going and kept spending,
and find...

finding and spending more
money to get it manufactured.

The major feeling was just

a sense of relief
that we had got there.

HILL:
The 10th of November 2015.

85 vials certified.

Three doses per person,

20 to 30 people
that would cover.

Not exactly
vaccinating the world, is it?

But it's where we started.

NARRATOR:
With these precious few doses

of R21,

the Oxford team began
small-scale human trials.

First, they mixed
the vaccine with a substance

called Matrix-M,

which helps
strengthen the immune response.

They injected 28 healthy adults,

and reported it induced

an antibody response comparable
to RTS,S

at a much lower vaccine dose.

Next, they purposely
exposed a few vaccinated people

to infectious mosquitoes,
in what's known

as a malaria challenge trial,

and found that they
were protected from malaria.

Such exciting
early results drew attention

beyond Oxford.

HILL:
Word got around, and we
academics talk at meetings

and you never know
who's in the room,

but my guess is there was
somebody

from the Serum Institute
of India.

And the next month,
Umesh Shaligram turned up here

wanting to talk about malaria.

Certainly, Oxford data

was very convincing early data.

So that certainly made a big

difference in our conviction.

HILL:
They'd heard about the initial
challenge results.

They came to us.

Normally,
we go begging to companies,

asking them to work with us.

We made a kind of
a handshake deal

that we could
manufacture the product.

That's how
the whole thing started.

♪ ♪

NARRATOR:
The Serum Institute of India

is the largest vaccine
manufacturer in the world.

Two-thirds of all babies
born globally

get at least one
of Serum's childhood vaccines,

made here in Pune.

It's made this family-run
company a global life-saver

and CEO Adar Poonawalla
a multi-billionaire.

ADAR POONAWALLA:
Every time we look at a vaccine,

the way we look at it is that
unless we can make

hundreds of millions of doses
for the whole world,

and unless it has that
need and demand,

we don't get into it.

Ah... Baitho.
What's happening?

(voiceover): These are very
large populations,

so they need a lot of vaccines.

It'd be unimaginable

if they had to pay $10,
$20 for a vaccine.

They wouldn't
be able to afford it.

We charge pennies on the dollar
for the vaccine.

But the economies of scale that
we operate at enable us

to do that and
still make a modest profit.

You can go ahead with that.

♪ ♪

NARRATOR:
In 2017,

Serum took
over manufacturing R21,

and spent two years developing

a new, reliable method
to produce it at scale.

The team chose the West African
country Burkina Faso,

where around half the population
gets malaria each year,

for the vaccine's
first real-world test.

In 2019,
450 very young children,

the group most
in need of protection,

were vaccinated
in a Phase Two trial.

For success, these babies would
have to experience

no unexpected side effects

and there would need to be a
significant reduction

in malaria cases in those who
received R21.

♪ ♪

The UK team waited for news.

It was actually my
colleague Mehreen who said,

"Look at your email,
we've got the results."

77 percent efficacy, as good
as we could possibly have hoped.

I wasn't even sure that

I could quite believe what I was
reading.

You know,

we showed that the vaccine,

albeit just over six months,

had worked in

the target population,

in the target age group.

But if you've seen really
good results,

you know what's coming--
large scale, Phase Three trials.

Definitely
a very daunting prospect.

♪ ♪

NARRATOR:
Phase Three is the largest
clinical trial.

It will need to be
big enough to determine

if R21 can safely prevent
malaria

in thousands of children.

And this will cost
around $20 million.

Me and Adrian went almost every
door to door

and tried to search
for the funding.

Somebody should support us.

And we had really a tough time.

HILL:
We're fighting for funding
against people

dealing with other very
important medical diseases.

People are more likely to try
and invest in something

that sounds new
than the old idea

of making a vaccine against
malaria,

which has failed and failed
and failed over decades.

SHALIGRAM:
After a year's try,

I remember I said,
"Mr. Poonawalla, sir,

"I'm having a big
challenge of getting the funding

for the Phase Three."

And he said,
"No, no, don't worry,

"malaria is very close to my
heart

and I want to support
the Phase Three."

NARRATOR:
The Serum Institute CEO
agrees to fund the trial.

The results had demonstrated
that the vaccine

is giving you protection.

So instead of wasting time,

we just wanted
to get on with the work.

♪ ♪

NARRATOR:
In April 2021,

Phase Three trial preparations
begin in Burkina Faso, Mali,

Kenya, and here in Tanzania.

♪ ♪

Mehreen Datoo is a British
infectious disease doctor.

But her key role on the R21 team

is to oversee its ultimate test.

(people greeting each other)

DATOO:
What we wanted to propose
today to do

is a mockup vaccine preparation
for us,

just to check it's all
running smoothly.

NARRATOR:
Nearly 5,000 very young
children

are set to receive shots in the
Phase Three trial,

hundreds of them in Tanzania.

For every two children
that receive R21,

one child will
receive a control vaccine.

In this case,
a vaccine against rabies.

This should look just like R21,

but offer no protection
at all from malaria.

The rabies vaccine
is a good option because

it's not a vaccine that children
would normally receive

in that part of the world,

so it does provide
some benefits.

NARRATOR:
Crucially,

Mehreen and almost everyone
involved

is blind to which vaccine
each child receives.

So they must monitor cases of
malaria across the whole trial,

and only learn
much later if those cases

were in the R21 vaccine
or the control group.

The only people that are
unblinded

are the pharmacy team
who prepare the vaccine.

You want to make sure the whole
volume is covered.

(voiceover): The whole idea
of this is to not know

which vaccine the child has
received

to ensure there's no bias.

It means that, you know,

we will get
the most accurate data.

That's why
there's two of you to do it.

♪ ♪

(indistinct chatter)

My family
are actually from East Africa.

Unfortunately, when I was doing
some research there previously,

I got malaria
and I was very, very sick.

I basically
fainted and collapsed.

And then was
diagnosed with severe malaria.

I don't remember a lot
of it because

I was just very, very unwell.

I was in my early 20s,
so I can't even imagine

how it affects very young
children.

♪ ♪

NARRATOR:
Here in Tanzania,

Dr. Ally Olotu
is managing the vaccination

and monitoring of 600 children.

OLOTU (speaking Swahili):

WOMAN (speaking Swahili):

OLOTU:

OLOTU: Farhiya! Okay.

WOMAN: Irene.

OLOTU:

a precious cargo arrives at
the Kiwangwa clinic, from India.

After an initial
three doses of either R21

or the rabies control vaccine,

a one-year booster shot is now
being prepared

for Farhiya and the other trial
participants.

ZUHURA (translated):
I enrolled my child Farhiya in
the program

above all because they have
great services

and really take good care
of a sick child.

And they also have all the
tests,

so that was an incentive for me.

I'm really excited Farhiya

is one of the first to get
vaccinated.

NARRATOR:
For Zuhura,
vaccination is about much more

than simply preventing
her daughter from falling ill.

ZUHURA (translated):
We are a generation of
strong women.

My mother fought hard for us,

and she's still working hard
despite her age.

We're busy farming
as well as running

a small business selling bhajia
and mandazi.

Our livelihood depends on my
small business,

and when Farhiya falls sick,
I can't attend to it.

And when you take her to

the local clinic in Kiwangwa,

they won't treat you without

either medical insurance

or $5,000 in cash.

(speaking Swahili, laughing)

HUBA MOHAMEDI (translated):
Instead of spending money
to treat malaria,

whether for kids or adults,

you can buy food, vegetables,

and the like instead.

We'll be very grateful
for the vaccine.

(people chattering,
child cooing)

NARRATOR:
For families and scientists
alike,

vaccination day is special.

They all look relatively happy.
No one's crying!

They do.
Yeah, yep, absolutely.

DATOO:
It's really nice to see
the relationships

the trial team have
with the participants

and the caregivers,
because I think that makes it,

you know, almost a bit more
like family.

♪ ♪

MOHAMEDI (translated):
Farhiya being
in the vaccination trial

gives me joy.

She will set an example
for others.

(indistinct chatter,
child whimpering)

(cheers, applause)

NARRATOR:
After vaccination,

Farhiya and the other children
in the trial

are closely monitored
for signs of malaria.

The vaccine's success
or failure will depend

on how many malaria cases
occur in children

who received R21

versus the control vaccine.

While they wait for this result,
the team is also investigating

what the vaccine
is doing inside the body.

(baby crying)

For that, they have
to study the children's blood.

OLOTU:
We can now measure

the amount of antibodies
that are in the blood.

Some of this will be shipped
into a reference lab in Oxford,

where samples from other sites

which are
participating will be analyzed.

♪ ♪

NARRATOR:
As Phase Three
booster vaccinations proceed,

immunologist Katie Ewer

and her team are deluged
with these blood samples.

EWER:
There's absolutely loads
still to do.

I have a freezer
full of thousands of samples

from the Phase Three that we
haven't had a chance

to start looking at yet.

Having had very recently
the experience

of taking vaccines through
Phase Three for COVID,

where we had an enormous team
of people

and AstraZeneca working on it,

the contrast to the team
working on malaria,

where there are seven of us,

it's a very different
experience.

(equipment beeping)

We're under pressure
to start churning out some data.

So it's full speed ahead.

LISA STOCKDALE:
Is plate one up on mine
or is it on yours?

SAM MORYS:
No, but the folder's up.

NARRATOR:
The team needs to analyze the
children's antibody responses

to R21 and the control vaccine.

Immunologist Lisa Stockdale

is running a test called
an ELISA.

LISA STOCKDALE:
We've got quite a big variation,

some of the samples have quite
a lot of antibody

whereas some of them don't.

We're blinded to which group
people are in,

but in general, it looks like
the plate is developing well.

I've been doing
hundreds of these ELISA plates.

Hundreds and hundreds.
(chuckles)

NARRATOR:
To be effective,

R21 must prime the blood with
antibodies

that target
the malaria CSP protein.

But the team also needs
to know if those antibodies

can actually neutralize
real malaria parasites.

EWER:
We take the parasites out

by dissecting the mosquito.

So I'm just
gonna hold it with one hand.

Pull the head away gently.

Okay. So we have the head off.

You end up with two pairs
of salivary glands.

They look like
little fat sausages.

It's those little sacs

that have got the parasites in.

Aha! Got them.

NARRATOR:
The parasites are added to
lab-grown liver cells,

along with blood
from vaccinated children.

If the liver cells
do not become infected,

it suggests the antibodies

should protect the children,
too.

EWER:
It's just a lot of pressure

to get through all these
samples,

get the antibody data together.

Should we do both of them
together then?

Could do.

HILL:
I am getting emails

at 2:00 or 3:00 in the morning.

So a lot of people
are working super hard.

I'm a little bit anxious

that maybe we've had to push
them too hard

or we're too ambitious
in our timeline.

I'm exhausted.

I'm tired, I'm stressed,
I'm not sleeping,

uh, yeah, I'm probably not
a great person to be around

at the moment, if I'm honest.

NARRATOR:
All this lab effort is crucial

to understanding how R21 works.

But above all,
they need to know if the vaccine

protects enough
children in the real world.

After around a year of
closely monitoring the health

of all 4,800 Phase Three
children,

the wait is nearly over.

HILL:
The key Phase Three trial
is coming to the end point.

The statisticians have the data

and they are analyzing it
as we speak.

EWER:
You know, this is something

that we've all worked on for
years, so to be this close,

it's, it's kind of nauseatingly,

sickeningly anxiety-inducing,
really.

You know, we just don't know
what we're going to see.

And I think we'll be all really
relieved to get that result.

NARRATOR:
Eleven years after R21
was first made

here in the lab,
after seven years of trials,

over 20,000 vaccinations

and hundreds of thousands
of samples analyzed,

an answer.

HILL:
Even ups significance on
severe malaria.

EWER:
72 percent, bloody hell!

Wide confidence intervals,
but bloody hell, that's what...

(indistinct)
I mean that's...
yeah, absolutely.

Great.

(sighs)
Oh, God. Get me a drink!

(sighs)
Yeah.

So we have
the result of the Phase Three.

So, big moment, um...

As, as expected
from the Phase Two,

some really interesting
results in there.

But yeah, really good
and really reassuring

and, yeah, just very happy.

(joyous exhale)

(crying)

(sniffles)

(sighs)

Yeah. We're very happy.

Although it really didn't look
like it, but...

Yeah, it's just a moment I've
been waiting for for so long.

But, yeah, what we wanted
and what we hoped for.

So really good. Yeah.

♪ ♪

NARRATOR:
Barely a month later,

there's a global
medical conference in Seattle.

The promise of the initial
Phase Three trial result

is now sinking in.

Across the different ages
and locations

of children in the trial,

around a year after they were
first vaccinated,

R21 has reduced cases
of clinical malaria

by about 70 to 80 percent.

Hey, good morning!
Ah!

NARRATOR:
So the teams from
Oxford, Tanzania,

Kenya, Mali, and Burkina Faso

gather to prepare

to present their data
publicly for the first time.

HILL:
These people
are just extraordinary.

They are leaders in their field.

Hello! How are you?
Good to see you.

HILL:
The results that have
come in show

safety looks absolutely fine in
literally thousands of children.

And even more excitingly,

the efficacy,
the reaction was they cheered.

DICKO:
Very, very good news.

OLOTU:
You know, seeing the numbers
that was a moment of excitement.

Everybody was taken aback

and say, you know what?

Wow, this is, this is real.

This is, this is something.

When this result came out,
I was like, ah.

Oof. Ah!

This is, this is what I was
waiting for long.

on Wednesday we're going to try

and tell the world
about what we've found.

♪ ♪

DATOO:
We know our vaccine works,
we know we have good data.

I'm excited to see the response.

I hope everyone
is as excited as we are.

♪ ♪

(applause)

I am very pleased today
to be able to share with you

the first data

on the safety and efficacy of
R21/Matrix-M,

the new malaria vaccine.

(applause)

MATTHEW COLDIRON:
It was extremely exciting.

This is a vaccine that works,

that's going to be widely
available,

at a reasonable price,

and that could really,
really make a big difference.

It's trite to say gamechanger
but I really think it is.

ANNA LAST:
It's very encouraging news
that they have

the Serum Institute in Pune

who is going to be able to

really scale up the production
of a vaccine.

♪ ♪

NARRATOR:
For the team,

sharing their results
is a moment to savor.

R21 can't be
directly compared with RTS,S--

their trials were different--
but there's now no doubt

about this
new vaccine's potential.

The next step is evaluation

by the World Health
Organization.

Its approval will be essential.

Without it,
donor funds can't be used

for the vaccine's
roll-out across Africa.

It's a process
that can take years.

(news theme playing)

NARRATOR:
But six months later,

as W.H.O. deliberations
continue,

there's breaking news.

A day of pure elation for Ghana,
for science

and for all of humanity,

as the FDA has granted approval
to a new vaccine.

REPORTER: Ghana's government has
become the first in the world

to clear the roll-out
of malaria vaccine R21.

NARRATOR: Ghana's drug regulator
has reviewed the data on R21

and approved it for use,

signaling a clear and urgent
demand for this new vaccine.

Days later, Nigeria follows suit

and Angola looks to place
an order.

But there's still no certainty

that the W.H.O.
will approve the vaccine

and so unlock the necessary
funds.

Let's get into the
manufacturing, um,

details of how

to scale up
as soon as possible,

because now I think there's
a lot of excitement.

NARRATOR:
In Pune,

Serum's CEO has a
very big decision to make.

POONAWALLA:
How many doses
should we then make at risk?

I was thinking around
20 to 25 million doses.

Do you think that would be okay?

SHALIGRAM:
That is,
so five million Angola wants,

and Nigeria also wants
around five, ten million,

and Ghana around five,
ten million,

so 25 million is good enough.

Or should we make around
30 million to be safe?

I think so, we should try...

Fine, go ahead, do it.

Let me know what the costing

and the risk we're taking
in that is,

but let's just go ahead.

What's the expiry on that?

The expiry is about 18 months.

Yeah, that's a matter
of concern.

♪ ♪

NARRATOR:
Adar Poonawalla has just risked
over $100 million

to start production
of 30 million doses of R21.

They'll be offered
at the very low price

of under four dollars a dose.

The gamble is whether W.H.O.
approval

and sales will come before
the vaccine stockpile expires.

♪ ♪

POONAWALLA:
We've taken all the risk,
you know,

for the trials,
for manufacturing,

30 million doses, we just
hope that it's all worth it.

I wouldn't have the freedom

to make these sort of risky
decisions and bets

had I been accountable

to multiple stakeholders,
shareholders, banks, etcetera.

Here, it's just a few
people coming together

and quickly deciding
to go ahead on something.

Everything is now on W.H.O.

to approve the vaccine,
that's all we're waiting for,

and then we can roll it out.

NARRATOR:
In Serum's cold storage,

the shelves rapidly
begin to fill with R21.

R21.
R21 storage, yeah.

SHALIGRAM:
This is a place

where your heart fills with
a joy.

Because finally the product

which will get into the humans
is ready.

This entire cold room can

accommodate 40 million doses,

which means 10 million

children vaccination.

Amazing feeling.

♪ ♪

NARRATOR:
It's five months since Serum's
R21 production line started.

The team has been sharing

continually updated evidence
with the W.H.O.

that the vaccine
is safe and cost-effective.

And although R21's efficacy

does decrease a little over
time,

a booster dose bumps it back up.

And now...

HILL:
Hello!

NARRATOR:
They've been told to expect
an announcement.

TEDROS ADHANOM GHEBREYESUS:
Good morning, good afternoon
and good evening.

Today is a great day for health.

A great day for vaccines.

Almost exactly two years ago,

W.H.O. recommended the broad use

of the world's first malaria
vaccine called

RTS,S.

Today, it gives me great
pleasure

to announce that the W.H.O. is
recommending

a second vaccine

called R21/Matrix-M to prevent
malaria

in children at risk of the
disease.

NARRATOR:
The W.H.O. has approved R21,

for use in any African child

at risk of malaria,

a decision that should
trigger the release

of critical donor funds.

Congratulations!
What a great day.

OLOTU (on computer):
Congratulations to you, too.

DICKO (on computer):
This is really an historic day

for Africa, I think.

HILL:
We are not talking about
hundreds or thousands,

but over time,

well over a million lives saved.

It, it's just staggering and,
and hugely, hugely gratifying.

And you just feel, wow.

EWER:
Really happy, really relieved,

and, you know,
proud that we've got here.

You know this opens the door for
the next stage for the vaccine,

which is to get out there
into the real world,

and, and that's the bit that

I'm sort of most excited about,
really.

♪ ♪

OLOTU:
I'm dreaming for that day
to come

and I hope it will
come sooner than later.

And, uh, yeah.

It's, uh, yeah, this is what,
this is what I want to see.

This is what every parent
wants to see.

NARRATOR:
In the long term,

malaria vaccines
offer great hope.

With climate change
opening new frontiers

for malaria-carrying mosquitoes,

more and better vaccines
will be important

in Africa and elsewhere.

And perhaps one day malaria may
even follow smallpox

into the history books.

But in Tanzania right now,

for people like Zuhura Abasi
and her daughter,

R21's mass roll out in 2024
can't come soon enough.

ZUHURA (translated):
I'll be very happy once malaria

is no more.

That way my child will be
able to study properly.

Unlike today when kids miss
school for days

because of malaria.

(singing in Swahili)

ZUHURA:

FARHIYA AND ZUHURA:

ZUHURA:

FARHIYA AND ZUHURA:

ZUHURA:

Eh?

♪ ♪

♪ ♪

♪ ♪

♪ ♪

♪ ♪

♪ ♪