HIV and flu the vaccine strategy Seth Berkley

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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 a hundred million people in

the next 50 years he looked at the odds

of another world war of a massive

volcanic eruption even if an asteroid

hitting the earth but he placed the

likelihood of one such event above all

others at close to a hundred 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 sketch

here but the death toll is almost

certainly higher you know the problem is

is that 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

fifty to a hundred 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 her 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 the

vaccines now you know 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 work 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 which humans have no natural

immunity so let’s explore how vaccines

work they basically create a catch 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

a vaccine trains the body in advance how

to recognize and neutralize a specific

invader after HIV penetrates the body’s

new coastal barriers it infects immune

cells to replicate the invader draws the

attention of the immune systems

frontline 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 frontline 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 on to 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

[Music]

really cool video isn’t it the

antibodies that you just saw in this

video in action are the ones that make

most vaccines work so the real question

that is how do we ensure that your body

makes the exact ones that we need to

protect against flu and HIV the

principle 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 color spikes or 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 common 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 case with

an apparent mortality rate of 70% now

you know 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

any time now let’s take a look at HIV as

variable as flu is

HIV makes flu look like the Rock of

Gibralter the virus that causes AIDS is

the trickiest pathogens 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 are in 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 in 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 HIV infected individual now what does

this mean we saw earlier that HIV is

highly variable that a broadly

neutralizing antibody latches on and

disables multiple variations of

iris 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 on to 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 tie 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

on to many many variations of the virus

we know that they have to latch on to a

specific part so if we can figure out

the precise structure of that part

present that through a vaccine what we

hoped is we can prompt your immune

system to make these matching antibodies

and that would create a universal HIV

vaccine now it sounds easier it is

because the structure actually looks