Seth Berkley: HIV and flu -- the vaccine strategy

Do you worry about what is going to kill you?

Heart disease, cancer,

a car accident?

Most of us worry about things we can't control,

like war, terrorism,

the tragic earthquake that just occurred in Haiti.

But what really threatens humanity?

A few years ago, Professor Vaclav Smil

tried to calculate the probability

of sudden disasters

large enough to change history.

He called these,

"massively fatal discontinuities,"

meaning that they could kill

up to 100 million people

in the next 50 years.

He looked at the odds of another world war,

of a massive volcanic eruption,

even of an asteroid hitting the Earth.

But he placed the likelihood of one such event

above all others

at close to 100 percent,

and that is a severe flu pandemic.

Now, you might think of flu

as just a really bad cold,

but it can be a death sentence.

Every year, 36,000 people in the United States

die of seasonal flu.

In the developing world, the data is much sketchier

but the death toll is almost

certainly higher.

You know, the problem is if

this virus occasionally mutates

so dramatically,

it essentially is a new virus

and then we get a pandemic.

In 1918, a new virus appeared

that killed some 50 to 100 million people.

It spread like wildfire

and some died within hours of developing symptoms.

Are we safer today?

Well, we seem to have dodged

the deadly pandemic this year

that most of us feared,

but this threat could reappear at any time.

The good news is that

we're at a moment in time

when science, technology, globalization is converging

to create an unprecedented possibility:

the possibility to make history

by preventing infectious diseases

that still account for one-fifth of all deaths

and countless misery on Earth.

We can do this.

We're already preventing millions of deaths

with existing vaccines,

and if we get these to more people,

we can certainly save more lives.

But with new or better vaccines

for malaria, TB, HIV,

pneumonia, diarrhea, flu,

we could end suffering

that has been on the Earth since the beginning of time.

So, I'm here to trumpet vaccines for you.

But first, I have to explain why they're important

because vaccines, the power of them,

is really like a whisper.

When they work, they can make history,

but after a while

you can barely hear them.

Now, some of us are old enough

to have a small, circular scar on our arms

from an inoculation we received as children.

But when was the last time you worried about smallpox,

a disease that killed half a billion people last century

and no longer is with us?

Or polio? How many of you remember the iron lung?

We don't see scenes like this anymore

because of vaccines.

Now, it's interesting

because there are 30-odd diseases

that can be treated with vaccines now,

but we're still threatened by things like HIV and flu.

Why is that?

Well, here's the dirty little secret.

Until recently, we haven't had to know

exactly how a vaccine worked.

We knew they worked through old-fashioned trial and error.

You took a pathogen, you modified it,

you injected it into a person or an animal

and you saw what happened.

This worked well for most pathogens,

somewhat well for crafty bugs like flu,

but not at all for HIV,

for which humans have no natural immunity.

So let's explore how vaccines work.

They basically create a cache

of weapons for your immune system

which you can deploy when needed.

Now, when you get a viral infection,

what normally happens is it takes days or weeks

for your body to fight back

at full strength,

and that might be too late.

When you're pre-immunized,

what happens is you have forces in your body

pre-trained to recognize

and defeat specific foes.

So that's really how vaccines work.

Now, let's take a look at a video

that we're debuting at TED, for the first time,

on how an effective HIV vaccine might work.

(Music)

Narrator: A vaccine trains the body in advance

how to recognize and neutralize

a specific invader.

After HIV penetrates the body's mucosal barriers,

it infects immune cells to replicate.

The invader draws the attention

of the immune system's front-line troops.

Dendritic cells, or macrophages,

capture the virus and display pieces of it.

Memory cells generated by the HIV vaccine

are activated when they learn

HIV is present from the front-line troops.

These memory cells immediately deploy

the exact weapons needed.

Memory B cells turn into plasma cells,

which produce wave after wave

of the specific antibodies

that latch onto HIV

to prevent it from infecting cells,

while squadrons of killer T cells

seek out and destroy cells

that are already HIV infected.

The virus is defeated.

Without a vaccine,

these responses would have taken more than a week.

By that time, the battle against HIV

would already have been lost.

Seth Berkley: Really cool video, isn't it?

The antibodies you just saw in this video,

in action, are the ones that make most vaccines work.

So the real question then is:

How do we ensure that your body makes

the exact ones that we need to protect

against flu and HIV?

The principal challenge for both of these viruses

is that they're always changing.

So let's take a look at the flu virus.

In this rendering of the flu virus,

these different colored spikes are what it uses to infect you.

And also, what the antibodies use is a handle

to essentially grab and neutralize the virus.

When these mutate, they change their shape,

and the antibodies don't know what they're looking at anymore.

So that's why every year

you can catch a slightly different strain of flu.

It's also why in the spring,

we have to make a best guess

at which three strains are going to prevail the next year,

put those into a single vaccine

and rush those into production for the fall.

Even worse,

the most common influenza -- influenza A --

also infects animals

that live in close proximity to humans,

and they can recombine

in those particular animals.

In addition, wild aquatic birds

carry all known strains

of influenza.

So, you've got this situation:

In 2003,

we had an H5N1 virus

that jumped from birds into humans

in a few isolated cases

with an apparent mortality rate of 70 percent.

Now luckily, that particular virus,

although very scary at the time,

did not transmit from person to person

very easily.

This year's H1N1 threat

was actually a human, avian, swine mixture

that arose in Mexico.

It was easily transmitted,

but, luckily, was pretty mild.

And so, in a sense,

our luck is holding out,

but you know, another wild bird could fly over at anytime.

Now let's take a look at HIV.

As variable as flu is,

HIV makes flu

look like the Rock of Gibraltar.

The virus that causes AIDS

is the trickiest pathogen

scientists have ever confronted.

It mutates furiously,

it has decoys to evade the immune system,

it attacks the very cells that are trying to fight it

and it quickly hides itself

in your genome.

Here's a slide looking at

the genetic variation of flu

and comparing that to HIV,

a much wilder target.

In the video a moment ago,

you saw fleets of new viruses launching from infected cells.

Now realize that in a recently infected person,

there are millions of these ships;

each one is just slightly different.

Finding a weapon that recognizes

and sinks all of them

makes the job that much harder.

Now, in the 27 years since HIV

was identified as the cause of AIDS,

we've developed more drugs to treat HIV

than all other viruses put together.

These drugs aren't cures,

but they represent a huge triumph of science

because they take away the automatic death sentence

from a diagnosis of HIV,

at least for those who can access them.

The vaccine effort though is really quite different.

Large companies moved away from it

because they thought the science was so difficult

and vaccines were seen as poor business.

Many thought that it was just impossible to make an AIDS vaccine,

but today, evidence tells us otherwise.

In September,

we had surprising but exciting findings

from a clinical trial that took place in Thailand.

For the first time, we saw an AIDS vaccine work in humans --

albeit, quite modestly --

and that particular vaccine was made

almost a decade ago.

Newer concepts and early testing now

show even greater promise in the best of our animal models.

But in the past few months, researchers have also isolated

several new broadly neutralizing antibodies

from the blood of an HIV infected individual.

Now, what does this mean?

We saw earlier that HIV

is highly variable,

that a broad neutralizing antibody

latches on and disables

multiple variations of the virus.

If you take these and you put them

in the best of our monkey models,

they provide full protection from infection.

In addition, these researchers found

a new site on HIV

where the antibodies can grab onto,

and what's so special about this spot

is that it changes very little

as the virus mutates.

It's like, as many times

as the virus changes its clothes,

it's still wearing the same socks,

and now our job is to make sure

we get the body to really hate those socks.

So what we've got is a situation.

The Thai results tell us

we can make an AIDS vaccine,

and the antibody findings

tell us how we might do that.

This strategy, working backwards

from an antibody to create a vaccine candidate,

has never been done before in vaccine research.

It's called retro-vaccinology,

and its implications extend

way beyond that of just HIV.

So think of it this way.

We've got these new antibodies we've identified,

and we know that they latch onto many, many variations of the virus.

We know that they have to latch onto a specific part,

so if we can figure out the precise structure of that part,

present that through a vaccine,

what we hope is we can prompt

your immune system to make these matching antibodies.

And that would create

a universal HIV vaccine.

Now, it sounds easier than it is

because the structure actually looks more like

this blue antibody diagram

attached to its yellow binding site,

and as you can imagine, these three-dimensional structures

are much harder to work on.

And if you guys have ideas to help us solve this,

we'd love to hear about it.

But, you know, the research that has occurred from HIV now

has really helped with innovation with other diseases.

So for instance, a biotechnology company

has now found broadly neutralizing

antibodies to influenza,

as well as a new antibody target on the flu virus.

They're currently making a cocktail --

an antibody cocktail -- that can be used to treat

severe, overwhelming cases of flu.

In the longer term, what they can do

is use these tools of retro-vaccinology

to make a preventive flu vaccine.

Now, retro-vaccinology is just one technique

within the ambit of so-called rational vaccine design.

Let me give you another example.

We talked about before the H and N spikes

on the surface of the flu virus.

Notice these other, smaller protuberances.

These are largely hidden from the immune system.

Now it turns out that these spots

also don't change much when the virus mutates.

If you can cripple these with specific antibodies,

you could cripple all versions of the flu.

So far, animal tests indicate

that such a vaccine could prevent severe disease,

although you might get a mild case.

So if this works in humans, what we're talking about

is a universal flu vaccine,

one that doesn't need to change every year

and would remove the threat of death.

We really could think of flu, then,

as just a bad cold.

Of course, the best vaccine imaginable

is only valuable to the extent

we get it to everyone who needs it.

So to do that, we have to combine

smart vaccine design with smart production methods

and, of course, smart delivery methods.

So I want you to think back a few months ago.

In June, the World Health Organization

declared the first global

flu pandemic in 41 years.

The U.S. government promised

150 million doses of vaccine

by October 15th for the flu peak.

Vaccines were promised to developing countries.

Hundreds of millions of dollars were spent

and flowed to accelerating vaccine manufacturing.

So what happened?

Well, we first figured out

how to make flu vaccines, how to produce them,

in the early 1940s.

It was a slow, cumbersome process

that depended on chicken eggs,

millions of living chicken eggs.

Viruses only grow in living things,

and so it turned out that, for flu,

chicken eggs worked really well.

For most strains, you could get one to two doses

of vaccine per egg.

Luckily for us,

we live in an era of breathtaking

biomedical advances.

So today, we get our flu vaccines from ...

chicken eggs,

(Laughter)

hundreds of millions of chicken eggs.

Almost nothing has changed.

The system is reliable

but the problem is you never know how well

a strain is going to grow.

This year's swine flu strain

grew very poorly in early production:

basically .6 doses per egg.

So, here's an alarming thought.

What if that wild bird flies by again?

You could see an avian strain

that would infect the poultry flocks,

and then we would have no eggs for our vaccines.

So, Dan [Barber], if you want

billions of chicken pellets

for your fish farm,

I know where to get them.

So right now, the world can produce

about 350 million doses

of flu vaccine for the three strains,

and we can up that to about 1.2 billion doses

if we want to target a single variant

like swine flu.

But this assumes that our factories are humming

because, in 2004,

the U.S. supply was cut in half

by contamination at one single plant.

And the process still takes

more than half a year.

So are we better prepared

than we were in 1918?

Well, with the new technologies emerging now,

I hope we can say definitively, "Yes."

Imagine we could produce enough flu vaccine

for everyone in the entire world

for less than half of what we're currently spending

now in the United States.

With a range of new technologies, we could.

Here's an example:

A company I'm engaged with has found

a specific piece of the H spike of flu

that sparks the immune system.

If you lop this off and attach it

to the tail of a different bacterium,

which creates a vigorous immune response,

they've created a very powerful flu fighter.

This vaccine is so small

it can be grown in a common bacteria, E. coli.

Now, as you know, bacteria reproduce quickly --

it's like making yogurt --

and so we could produce enough swine origin flu

for the entire world in a few factories, in a few weeks,

with no eggs,

for a fraction of the cost of current methods.

(Applause)

So here's a comparison of several of these new vaccine technologies.

And, aside from the radically increased production

and huge cost savings --

for example, the E. coli method I just talked about --

look at the time saved: this would be lives saved.

The developing world,

mostly left out of the current response,

sees the potential of these alternate technologies

and they're leapfrogging the West.

India, Mexico and others are already

making experimental flu vaccines,

and they may be the first place

we see these vaccines in use.

Because these technologies are so efficient

and relatively cheap,

billions of people can have access to lifesaving vaccines

if we can figure out how to deliver them.

Now think of where this leads us.

New infectious diseases

appear or reappear

every few years.

Some day, perhaps soon,

we'll have a virus that is going to threaten all of us.

Will we be quick enough to react

before millions die?

Luckily, this year's flu was relatively mild.

I say, "luckily" in part

because virtually no one in the developing world

was vaccinated.

So if we have the political and financial foresight

to sustain our investments,

we will master these and new tools of vaccinology,

and with these tools we can produce

enough vaccine for everyone at low cost

and ensure healthy productive lives.

No longer must flu have to kill half a million people a year.

No longer does AIDS

need to kill two million a year.

No longer do the poor and vulnerable

need to be threatened by infectious diseases,

or indeed, anybody.

Instead of having Vaclav Smil's

"massively fatal discontinuity" of life,

we can ensure

the continuity of life.

What the world needs now are these new vaccines,

and we can make it happen.

Thank you very much.

(Applause)

Chris Anderson: Thank you.

(Applause)

Thank you.

So, the science is changing.

In your mind, Seth -- I mean, you must dream about this --

what is the kind of time scale

on, let's start with HIV,

for a game-changing vaccine that's actually out there and usable?

SB: The game change can come at any time,

because the problem we have now is

we've shown we can get a vaccine to work in humans;

we just need a better one.

And with these types of antibodies, we know humans can make them.

So, if we can figure out how to do that,

then we have the vaccine,

and what's interesting is there already is

some evidence that we're beginning to crack that problem.

So, the challenge is full speed ahead.

CA: In your gut, do you think it's probably going to be at least another five years?

SB: You know, everybody says it's 10 years,

but it's been 10 years every 10 years.

So I hate to put a timeline

on scientific innovation,

but the investments that have occurred are now paying dividends.

CA: And that's the same with universal flu vaccine, the same kind of thing?

SB: I think flu is different. I think what happened with flu is

we've got a bunch -- I just showed some of this --

a bunch of really cool and useful technologies that are ready to go now.

They look good. The problem has been that,

what we did is we invested in traditional technologies

because that's what we were comfortable with.

You also can use adjuvants, which are chemicals you mix.

That's what Europe is doing, so we could have diluted out

our supply of flu and made more available,

but, going back to what Michael Specter said,

the anti-vaccine crowd didn't really want that to happen.

CA: And malaria's even further behind?

SB: No, malaria, there is a candidate

that actually showed efficacy in an earlier trial

and is currently in phase three trials now.

It probably isn't the perfect vaccine, but it's moving along.

CA: Seth, most of us do work where every month,

we produce something;

we get that kind of gratification.

You've been slaving away at this for more than a decade,

and I salute you and your colleagues for what you do.

The world needs people like you. Thank you.

SB: Thank you.

(Applause)