HIV and flu the vaccine strategy Seth Berkley
[Music]
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
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 royal neutralizing
antibodies to influenza as well as a new
antibody target on the flu virus they’re
currently making a cocktail in antibody
cocktail that can be used to treat
severe overwhelming cases of flu now 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 these with
specific antibodies you could
all versions of the flu so far animal
tests indicate that such a vaccine could
prevent severe disease although 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 US
government promised 150 million doses of
vaccine by October 15 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
hundreds of millions of chicken eggs you
know almost nothing has changed you know
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 point six 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 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 US 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 the new technology is
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
so here’s a comparison of several of
these new vaccine technologies and aside
from the radically increased production
and huge cost savings for an example the
e.coli method I just talked about look
at the time save this would be live
saved the developing world mostly left
out of the current response sees the
potential of these alternate
technologies and their leap frogging 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 life-saving 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 someday 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 X and ology 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 2 million a year
no longer do the poor and vulnerable
need to be threatened by infectious
diseases or indeed anybody instead of
having vacuous meals 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
thank you
so
thank you so the science is changing in
your mind Seth I mean you you must dream
about this what is the kind of timescale
on let’s start with HIV for a
game-changing vaccine that’s actually
out there and usable the game change can
come in at any time because this is the
problem we have now as we’ve shown we
can get a vaccine to work in humans we
just need a better one and with these
types of annuals 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 being to crack that
problem so the challenge is full speed
and your gut do you think it’s probably
gonna be at least another five years you
know that everybody says it’s ten years
but it’s been ten years every ten years
so I hate to put I hate to put a
timeline on scientific innovation but
the investments that have occurred are
now paying dividends and that’s the same
with universal flu vaccine the same kind
of thing I think flu is different I
think what happened with flu is we’ve
got a bunch of Tigers shown some of
there’s 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 adjuvant 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 mike respector said you know the
anti vaccine crowd didn’t really want
that to happen and malaria is even
further behind all 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
sothe myths let’s do work where every
month we kind of you know we produce
something we get that kind of
gratification you’ve been slaving away
at this for more than a decade and I
just you know I salute you and your
colleagues for what you do the world
needs people like you thank you thank
you
you