21:37
TED2010

Seth Berkley: HIV and flu -- the vaccine strategy

Filmed:

Seth Berkley explains how smart advances in vaccine design, production and distribution are bringing us closer than ever to eliminating a host of global threats -- from AIDS to malaria to flu pandemics.

- Vaccine visionary
Epidemiologist Seth Berkley is leading the charge to make sure vaccines are available to everyone, including those living in the developing world. Full bio

Do you worry about what is going to kill you?
00:17
Heart disease, cancer,
00:20
a car accident?
00:22
Most of us worry about things we can't control,
00:24
like war, terrorism,
00:27
the tragic earthquake that just occurred in Haiti.
00:29
But what really threatens humanity?
00:32
A few years ago, Professor Vaclav Smil
00:36
tried to calculate the probability
00:38
of sudden disasters
00:40
large enough to change history.
00:42
He called these,
00:44
"massively fatal discontinuities,"
00:46
meaning that they could kill
00:48
up to 100 million people
00:50
in the next 50 years.
00:52
He looked at the odds of another world war,
00:54
of a massive volcanic eruption,
00:57
even of an asteroid hitting the Earth.
00:59
But he placed the likelihood of one such event
01:01
above all others
01:04
at close to 100 percent,
01:06
and that is a severe flu pandemic.
01:08
Now, you might think of flu
01:12
as just a really bad cold,
01:14
but it can be a death sentence.
01:17
Every year, 36,000 people in the United States
01:19
die of seasonal flu.
01:22
In the developing world, the data is much sketchier
01:25
but the death toll is almost
01:27
certainly higher.
01:29
You know, the problem is if
01:31
this virus occasionally mutates
01:33
so dramatically,
01:35
it essentially is a new virus
01:37
and then we get a pandemic.
01:39
In 1918, a new virus appeared
01:43
that killed some 50 to 100 million people.
01:46
It spread like wildfire
01:49
and some died within hours of developing symptoms.
01:51
Are we safer today?
01:54
Well, we seem to have dodged
01:56
the deadly pandemic this year
01:58
that most of us feared,
02:00
but this threat could reappear at any time.
02:02
The good news is that
02:05
we're at a moment in time
02:07
when science, technology, globalization is converging
02:09
to create an unprecedented possibility:
02:12
the possibility to make history
02:14
by preventing infectious diseases
02:16
that still account for one-fifth of all deaths
02:19
and countless misery on Earth.
02:22
We can do this.
02:25
We're already preventing millions of deaths
02:27
with existing vaccines,
02:29
and if we get these to more people,
02:31
we can certainly save more lives.
02:33
But with new or better vaccines
02:36
for malaria, TB, HIV,
02:38
pneumonia, diarrhea, flu,
02:41
we could end suffering
02:43
that has been on the Earth since the beginning of time.
02:45
So, I'm here to trumpet vaccines for you.
02:48
But first, I have to explain why they're important
02:50
because vaccines, the power of them,
02:53
is really like a whisper.
02:56
When they work, they can make history,
02:58
but after a while
03:00
you can barely hear them.
03:02
Now, some of us are old enough
03:04
to have a small, circular scar on our arms
03:07
from an inoculation we received as children.
03:10
But when was the last time you worried about smallpox,
03:13
a disease that killed half a billion people last century
03:16
and no longer is with us?
03:19
Or polio? How many of you remember the iron lung?
03:21
We don't see scenes like this anymore
03:24
because of vaccines.
03:27
Now, it's interesting
03:29
because there are 30-odd diseases
03:31
that can be treated with vaccines now,
03:34
but we're still threatened by things like HIV and flu.
03:36
Why is that?
03:39
Well, here's the dirty little secret.
03:41
Until recently, we haven't had to know
03:43
exactly how a vaccine worked.
03:45
We knew they worked through old-fashioned trial and error.
03:48
You took a pathogen, you modified it,
03:51
you injected it into a person or an animal
03:53
and you saw what happened.
03:56
This worked well for most pathogens,
03:58
somewhat well for crafty bugs like flu,
04:01
but not at all for HIV,
04:04
for which humans have no natural immunity.
04:06
So let's explore how vaccines work.
04:09
They basically create a cache
04:12
of weapons for your immune system
04:14
which you can deploy when needed.
04:16
Now, when you get a viral infection,
04:19
what normally happens is it takes days or weeks
04:22
for your body to fight back
04:24
at full strength,
04:26
and that might be too late.
04:28
When you're pre-immunized,
04:30
what happens is you have forces in your body
04:32
pre-trained to recognize
04:34
and defeat specific foes.
04:36
So that's really how vaccines work.
04:38
Now, let's take a look at a video
04:40
that we're debuting at TED, for the first time,
04:42
on how an effective HIV vaccine might work.
04:45
(Music)
04:49
Narrator: A vaccine trains the body in advance
04:55
how to recognize and neutralize
04:57
a specific invader.
04:59
After HIV penetrates the body's mucosal barriers,
05:01
it infects immune cells to replicate.
05:04
The invader draws the attention
05:08
of the immune system's front-line troops.
05:10
Dendritic cells, or macrophages,
05:12
capture the virus and display pieces of it.
05:14
Memory cells generated by the HIV vaccine
05:18
are activated when they learn
05:21
HIV is present from the front-line troops.
05:23
These memory cells immediately deploy
05:26
the exact weapons needed.
05:29
Memory B cells turn into plasma cells,
05:32
which produce wave after wave
05:35
of the specific antibodies
05:37
that latch onto HIV
05:39
to prevent it from infecting cells,
05:41
while squadrons of killer T cells
05:43
seek out and destroy cells
05:45
that are already HIV infected.
05:47
The virus is defeated.
05:50
Without a vaccine,
05:52
these responses would have taken more than a week.
05:54
By that time, the battle against HIV
05:57
would already have been lost.
05:59
Seth Berkley: Really cool video, isn't it?
06:08
The antibodies you just saw in this video,
06:11
in action, are the ones that make most vaccines work.
06:14
So the real question then is:
06:17
How do we ensure that your body makes
06:19
the exact ones that we need to protect
06:21
against flu and HIV?
06:23
The principal challenge for both of these viruses
06:25
is that they're always changing.
06:28
So let's take a look at the flu virus.
06:30
In this rendering of the flu virus,
06:33
these different colored spikes are what it uses to infect you.
06:35
And also, what the antibodies use is a handle
06:38
to essentially grab and neutralize the virus.
06:41
When these mutate, they change their shape,
06:44
and the antibodies don't know what they're looking at anymore.
06:47
So that's why every year
06:50
you can catch a slightly different strain of flu.
06:53
It's also why in the spring,
06:56
we have to make a best guess
06:58
at which three strains are going to prevail the next year,
07:00
put those into a single vaccine
07:03
and rush those into production for the fall.
07:05
Even worse,
07:08
the most common influenza -- influenza A --
07:10
also infects animals
07:13
that live in close proximity to humans,
07:15
and they can recombine
07:17
in those particular animals.
07:19
In addition, wild aquatic birds
07:21
carry all known strains
07:23
of influenza.
07:25
So, you've got this situation:
07:27
In 2003,
07:29
we had an H5N1 virus
07:31
that jumped from birds into humans
07:34
in a few isolated cases
07:37
with an apparent mortality rate of 70 percent.
07:39
Now luckily, that particular virus,
07:42
although very scary at the time,
07:45
did not transmit from person to person
07:47
very easily.
07:49
This year's H1N1 threat
07:51
was actually a human, avian, swine mixture
07:54
that arose in Mexico.
07:58
It was easily transmitted,
08:00
but, luckily, was pretty mild.
08:02
And so, in a sense,
08:05
our luck is holding out,
08:07
but you know, another wild bird could fly over at anytime.
08:09
Now let's take a look at HIV.
08:13
As variable as flu is,
08:15
HIV makes flu
08:17
look like the Rock of Gibraltar.
08:19
The virus that causes AIDS
08:21
is the trickiest pathogen
08:23
scientists have ever confronted.
08:25
It mutates furiously,
08:27
it has decoys to evade the immune system,
08:29
it attacks the very cells that are trying to fight it
08:31
and it quickly hides itself
08:34
in your genome.
08:36
Here's a slide looking at
08:38
the genetic variation of flu
08:40
and comparing that to HIV,
08:42
a much wilder target.
08:44
In the video a moment ago,
08:47
you saw fleets of new viruses launching from infected cells.
08:49
Now realize that in a recently infected person,
08:52
there are millions of these ships;
08:55
each one is just slightly different.
08:57
Finding a weapon that recognizes
08:59
and sinks all of them
09:01
makes the job that much harder.
09:03
Now, in the 27 years since HIV
09:05
was identified as the cause of AIDS,
09:08
we've developed more drugs to treat HIV
09:11
than all other viruses put together.
09:13
These drugs aren't cures,
09:16
but they represent a huge triumph of science
09:18
because they take away the automatic death sentence
09:20
from a diagnosis of HIV,
09:22
at least for those who can access them.
09:24
The vaccine effort though is really quite different.
09:27
Large companies moved away from it
09:30
because they thought the science was so difficult
09:32
and vaccines were seen as poor business.
09:35
Many thought that it was just impossible to make an AIDS vaccine,
09:38
but today, evidence tells us otherwise.
09:41
In September,
09:44
we had surprising but exciting findings
09:46
from a clinical trial that took place in Thailand.
09:49
For the first time, we saw an AIDS vaccine work in humans --
09:52
albeit, quite modestly --
09:55
and that particular vaccine was made
09:58
almost a decade ago.
10:00
Newer concepts and early testing now
10:02
show even greater promise in the best of our animal models.
10:04
But in the past few months, researchers have also isolated
10:09
several new broadly neutralizing antibodies
10:12
from the blood of an HIV infected individual.
10:15
Now, what does this mean?
10:18
We saw earlier that HIV
10:20
is highly variable,
10:22
that a broad neutralizing antibody
10:24
latches on and disables
10:26
multiple variations of the virus.
10:28
If you take these and you put them
10:31
in the best of our monkey models,
10:33
they provide full protection from infection.
10:35
In addition, these researchers found
10:38
a new site on HIV
10:40
where the antibodies can grab onto,
10:42
and what's so special about this spot
10:44
is that it changes very little
10:46
as the virus mutates.
10:48
It's like, as many times
10:50
as the virus changes its clothes,
10:52
it's still wearing the same socks,
10:54
and now our job is to make sure
10:55
we get the body to really hate those socks.
10:58
So what we've got is a situation.
11:01
The Thai results tell us
11:03
we can make an AIDS vaccine,
11:05
and the antibody findings
11:07
tell us how we might do that.
11:09
This strategy, working backwards
11:11
from an antibody to create a vaccine candidate,
11:14
has never been done before in vaccine research.
11:16
It's called retro-vaccinology,
11:19
and its implications extend
11:22
way beyond that of just HIV.
11:24
So think of it this way.
11:27
We've got these new antibodies we've identified,
11:29
and we know that they latch onto many, many variations of the virus.
11:32
We know that they have to latch onto a specific part,
11:35
so if we can figure out the precise structure of that part,
11:38
present that through a vaccine,
11:41
what we hope is we can prompt
11:43
your immune system to make these matching antibodies.
11:45
And that would create
11:48
a universal HIV vaccine.
11:50
Now, it sounds easier than it is
11:52
because the structure actually looks more like
11:54
this blue antibody diagram
11:56
attached to its yellow binding site,
11:58
and as you can imagine, these three-dimensional structures
12:00
are much harder to work on.
12:02
And if you guys have ideas to help us solve this,
12:04
we'd love to hear about it.
12:06
But, you know, the research that has occurred from HIV now
12:08
has really helped with innovation with other diseases.
12:11
So for instance, a biotechnology company
12:14
has now found broadly neutralizing
12:16
antibodies to influenza,
12:18
as well as a new antibody target on the flu virus.
12:20
They're currently making a cocktail --
12:23
an antibody cocktail -- that can be used to treat
12:26
severe, overwhelming cases of flu.
12:29
In the longer term, what they can do
12:32
is use these tools of retro-vaccinology
12:34
to make a preventive flu vaccine.
12:36
Now, retro-vaccinology is just one technique
12:39
within the ambit of so-called rational vaccine design.
12:42
Let me give you another example.
12:45
We talked about before the H and N spikes
12:48
on the surface of the flu virus.
12:50
Notice these other, smaller protuberances.
12:52
These are largely hidden from the immune system.
12:55
Now it turns out that these spots
12:58
also don't change much when the virus mutates.
13:00
If you can cripple these with specific antibodies,
13:03
you could cripple all versions of the flu.
13:05
So far, animal tests indicate
13:08
that such a vaccine could prevent severe disease,
13:10
although you might get a mild case.
13:13
So if this works in humans, what we're talking about
13:15
is a universal flu vaccine,
13:18
one that doesn't need to change every year
13:20
and would remove the threat of death.
13:22
We really could think of flu, then,
13:25
as just a bad cold.
13:27
Of course, the best vaccine imaginable
13:30
is only valuable to the extent
13:32
we get it to everyone who needs it.
13:34
So to do that, we have to combine
13:36
smart vaccine design with smart production methods
13:38
and, of course, smart delivery methods.
13:41
So I want you to think back a few months ago.
13:44
In June, the World Health Organization
13:46
declared the first global
13:49
flu pandemic in 41 years.
13:51
The U.S. government promised
13:53
150 million doses of vaccine
13:55
by October 15th for the flu peak.
13:57
Vaccines were promised to developing countries.
13:59
Hundreds of millions of dollars were spent
14:01
and flowed to accelerating vaccine manufacturing.
14:03
So what happened?
14:06
Well, we first figured out
14:08
how to make flu vaccines, how to produce them,
14:10
in the early 1940s.
14:13
It was a slow, cumbersome process
14:15
that depended on chicken eggs,
14:18
millions of living chicken eggs.
14:21
Viruses only grow in living things,
14:24
and so it turned out that, for flu,
14:26
chicken eggs worked really well.
14:28
For most strains, you could get one to two doses
14:30
of vaccine per egg.
14:33
Luckily for us,
14:35
we live in an era of breathtaking
14:37
biomedical advances.
14:39
So today, we get our flu vaccines from ...
14:41
chicken eggs,
14:44
(Laughter)
14:46
hundreds of millions of chicken eggs.
14:48
Almost nothing has changed.
14:50
The system is reliable
14:52
but the problem is you never know how well
14:54
a strain is going to grow.
14:56
This year's swine flu strain
14:59
grew very poorly in early production:
15:01
basically .6 doses per egg.
15:04
So, here's an alarming thought.
15:08
What if that wild bird flies by again?
15:10
You could see an avian strain
15:12
that would infect the poultry flocks,
15:14
and then we would have no eggs for our vaccines.
15:16
So, Dan [Barber], if you want
15:18
billions of chicken pellets
15:20
for your fish farm,
15:22
I know where to get them.
15:24
So right now, the world can produce
15:26
about 350 million doses
15:28
of flu vaccine for the three strains,
15:30
and we can up that to about 1.2 billion doses
15:33
if we want to target a single variant
15:36
like swine flu.
15:38
But this assumes that our factories are humming
15:40
because, in 2004,
15:43
the U.S. supply was cut in half
15:45
by contamination at one single plant.
15:47
And the process still takes
15:50
more than half a year.
15:52
So are we better prepared
15:54
than we were in 1918?
15:56
Well, with the new technologies emerging now,
15:58
I hope we can say definitively, "Yes."
16:00
Imagine we could produce enough flu vaccine
16:02
for everyone in the entire world
16:05
for less than half of what we're currently spending
16:08
now in the United States.
16:10
With a range of new technologies, we could.
16:12
Here's an example:
16:15
A company I'm engaged with has found
16:17
a specific piece of the H spike of flu
16:19
that sparks the immune system.
16:21
If you lop this off and attach it
16:23
to the tail of a different bacterium,
16:25
which creates a vigorous immune response,
16:28
they've created a very powerful flu fighter.
16:30
This vaccine is so small
16:32
it can be grown in a common bacteria, E. coli.
16:34
Now, as you know, bacteria reproduce quickly --
16:37
it's like making yogurt --
16:40
and so we could produce enough swine origin flu
16:42
for the entire world in a few factories, in a few weeks,
16:44
with no eggs,
16:47
for a fraction of the cost of current methods.
16:49
(Applause)
16:52
So here's a comparison of several of these new vaccine technologies.
16:57
And, aside from the radically increased production
17:00
and huge cost savings --
17:03
for example, the E. coli method I just talked about --
17:05
look at the time saved: this would be lives saved.
17:08
The developing world,
17:11
mostly left out of the current response,
17:13
sees the potential of these alternate technologies
17:16
and they're leapfrogging the West.
17:19
India, Mexico and others are already
17:21
making experimental flu vaccines,
17:23
and they may be the first place
17:25
we see these vaccines in use.
17:27
Because these technologies are so efficient
17:29
and relatively cheap,
17:32
billions of people can have access to lifesaving vaccines
17:34
if we can figure out how to deliver them.
17:37
Now think of where this leads us.
17:39
New infectious diseases
17:41
appear or reappear
17:43
every few years.
17:45
Some day, perhaps soon,
17:47
we'll have a virus that is going to threaten all of us.
17:49
Will we be quick enough to react
17:52
before millions die?
17:54
Luckily, this year's flu was relatively mild.
17:56
I say, "luckily" in part
17:59
because virtually no one in the developing world
18:01
was vaccinated.
18:04
So if we have the political and financial foresight
18:06
to sustain our investments,
18:09
we will master these and new tools of vaccinology,
18:11
and with these tools we can produce
18:14
enough vaccine for everyone at low cost
18:16
and ensure healthy productive lives.
18:18
No longer must flu have to kill half a million people a year.
18:21
No longer does AIDS
18:24
need to kill two million a year.
18:26
No longer do the poor and vulnerable
18:28
need to be threatened by infectious diseases,
18:30
or indeed, anybody.
18:33
Instead of having Vaclav Smil's
18:35
"massively fatal discontinuity" of life,
18:38
we can ensure
18:41
the continuity of life.
18:43
What the world needs now are these new vaccines,
18:45
and we can make it happen.
18:47
Thank you very much.
18:49
(Applause)
18:51
Chris Anderson: Thank you.
18:59
(Applause)
19:01
Thank you.
19:07
So, the science is changing.
19:09
In your mind, Seth -- I mean, you must dream about this --
19:12
what is the kind of time scale
19:15
on, let's start with HIV,
19:18
for a game-changing vaccine that's actually out there and usable?
19:20
SB: The game change can come at any time,
19:24
because the problem we have now is
19:26
we've shown we can get a vaccine to work in humans;
19:28
we just need a better one.
19:30
And with these types of antibodies, we know humans can make them.
19:32
So, if we can figure out how to do that,
19:34
then we have the vaccine,
19:36
and what's interesting is there already is
19:38
some evidence that we're beginning to crack that problem.
19:40
So, the challenge is full speed ahead.
19:42
CA: In your gut, do you think it's probably going to be at least another five years?
19:44
SB: You know, everybody says it's 10 years,
19:46
but it's been 10 years every 10 years.
19:48
So I hate to put a timeline
19:50
on scientific innovation,
19:52
but the investments that have occurred are now paying dividends.
19:54
CA: And that's the same with universal flu vaccine, the same kind of thing?
19:57
SB: I think flu is different. I think what happened with flu is
20:00
we've got a bunch -- I just showed some of this --
20:02
a bunch of really cool and useful technologies that are ready to go now.
20:04
They look good. The problem has been that,
20:07
what we did is we invested in traditional technologies
20:09
because that's what we were comfortable with.
20:12
You also can use adjuvants, which are chemicals you mix.
20:14
That's what Europe is doing, so we could have diluted out
20:17
our supply of flu and made more available,
20:19
but, going back to what Michael Specter said,
20:21
the anti-vaccine crowd didn't really want that to happen.
20:24
CA: And malaria's even further behind?
20:27
SB: No, malaria, there is a candidate
20:29
that actually showed efficacy in an earlier trial
20:31
and is currently in phase three trials now.
20:34
It probably isn't the perfect vaccine, but it's moving along.
20:36
CA: Seth, most of us do work where every month,
20:39
we produce something;
20:41
we get that kind of gratification.
20:43
You've been slaving away at this for more than a decade,
20:45
and I salute you and your colleagues for what you do.
20:48
The world needs people like you. Thank you.
20:51
SB: Thank you.
20:53
(Applause)
20:55

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About the Speaker:

Seth Berkley - Vaccine visionary
Epidemiologist Seth Berkley is leading the charge to make sure vaccines are available to everyone, including those living in the developing world.

Why you should listen

Seth Berkley is an epidemiologist and the CEO of Gavi, the Vaccine Alliance, the global health organization protecting lives by improving access to vaccines in developing countries. Seth joined Gavi in 2011 in a period of rapid acceleration of Gavi’s programs. Now, with more than half a billion children immunized, he is leading Gavi’s efforts to reach a further 300 million children in the next five years and build sustainability into country immunization programs. Prior to Gavi, he spearheaded the development of vaccines for HIV as founder and CEO of the International AIDS Vaccine Initiative.

More profile about the speaker
Seth Berkley | Speaker | TED.com