TED Talks-Seth Berkley: HIV and flu-the vaccine strategy

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Transcript:


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 Smiltried to calculate the probabilityof sudden disasterslarge enough to change history.He called these,"massively fatal discontinuities,"meaning that they could killup to 100 million peoplein 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 eventabove all othersat close to 100 percent,and that is a severe flu pandemic.Now, you might think of fluas just a really bad cold,but it can be a death sentence.Every year, 36,000 people in the United Statesdie of seasonal flu.In the developing world, the data is much sketchierbut the death toll is almostcertainly higher.You know, the problem is ifthis virus occasionally mutatesso dramatically,it essentially is a new virusand then we get a pandemic.

In 1918, a new virus appearedthat killed some 50 to 100 million people.It spread like wildfireand some died within hours of developing symptoms.Are we safer today?Well, we seem to have dodgedthe deadly pandemic this yearthat most of us feared,but this threat could reappear at any time.The good news is thatwe're at a moment in timewhen science, technology, globalization is convergingto create an unprecedented possibility:the possibility to make historyby preventing infectious diseasesthat still account for one-fifth of all deathsand countless misery on Earth.We can do this.We're already preventing millions of deathswith existing vaccines,and if we get these to more people,we can certainly save more lives.But with new or better vaccinesfor malaria, TB, HIV,pneumonia, diarrhea, flu,we could end sufferingthat 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 importantbecause vaccines, the power of them,is really like a whisper.When they work, they can make history,but after a whileyou can barely hear them.Now, some of us are old enoughto have a small, circular scar on our armsfrom 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 centuryand no longer is with us?Or polio? How many of you remember the iron lung?We don't see scenes like this anymorebecause of vaccines.

Now, it's interestingbecause there are 30-odd diseasesthat 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 knowexactly 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 animaland 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 cacheof weapons for your immune systemwhich you can deploy when needed.Now, when you get a viral infection,what normally happens is it takes days or weeksfor your body to fight backat full strength,and that might be too late.When you're pre-immunized,what happens is you have forces in your bodypre-trained to recognizeand defeat specific foes.So that's really how vaccines work.Now, let's take a look at a videothat 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 advancehow to recognize and neutralizea specific invader.After HIV penetrates the body's mucosal barriers,it infects immune cells to replicate.The invader draws the attentionof 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 vaccineare activated when they learnHIV is present from the front-line troops.These memory cells immediately deploythe exact weapons needed.Memory B cells turn into plasma cells,which produce wave after waveof the specific antibodiesthat latch onto HIVto prevent it from infecting cells,while squadrons of killer T cellsseek out and destroy cellsthat 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 HIVwould 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 makesthe exact ones that we need to protectagainst flu and HIV?The principal challenge for both of these virusesis 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 handleto 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 yearyou can catch a slightly different strain of flu.It's also why in the spring,we have to make a best guessat which three strains are going to prevail the next year,put those into a single vaccineand rush those into production for the fall.

Even worse,the most common influenza -- influenza A --also infects animalsthat live in close proximity to humans,and they can recombinein those particular animals.In addition, wild aquatic birdscarry all known strainsof influenza.So, you've got this situation:In 2003,we had an H5N1 virusthat jumped from birds into humansin a few isolated caseswith an apparent mortality rate of 70 percent.Now luckily, that particular virus,although very scary at the time,did not transmit from person to personvery easily.This year's H1N1 threatwas actually a human, avian, swine mixturethat 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 flulook like the Rock of Gibraltar.The virus that causes AIDSis the trickiest pathogenscientists have ever confronted.It mutates furiously,it has decoys to evade the immune system,it attacks the very cells that are trying to fight itand it quickly hides itselfin your genome.Here's a slide looking atthe genetic variation of fluand 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 recognizesand sinks all of themmakes the job that much harder.

Now, in the 27 years since HIVwas identified as the cause of AIDS,we've developed more drugs to treat HIVthan all other viruses put together.These drugs aren't cures,but they represent a huge triumph of sciencebecause they take away the automatic death sentencefrom 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 itbecause they thought the science was so difficultand 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 findingsfrom 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 madealmost a decade ago.Newer concepts and early testing nowshow even greater promise in the best of our animal models.But in the past few months, researchers have also isolatedseveral new broadly neutralizing antibodiesfrom the blood of an HIV infected individual.Now, what does this mean?We saw earlier that HIVis highly variable,that a broad neutralizing antibodylatches on and disablesmultiple variations of the virus.If you take these and you put themin the best of our monkey models,they provide full protection from infection.In addition, these researchers founda new site on HIVwhere the antibodies can grab onto,and what's so special about this spotis that it changes very littleas the virus mutates.It's like, as many timesas the virus changes its clothes,it's still wearing the same socks,and now our job is to make surewe get the body to really hate those socks.

So what we've got is a situation.The Thai results tell uswe can make an AIDS vaccine,and the antibody findingstell us how we might do that.This strategy, working backwardsfrom an antibody to create a vaccine candidate,has never been done before in vaccine research.It's called retro-vaccinology,and its implications extendway 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 promptyour immune system to make these matching antibodies.And that would createa universal HIV vaccine.Now, it sounds easier than it isbecause the structure actually looks more likethis blue antibody diagramattached to its yellow binding site,and as you can imagine, these three-dimensional structuresare 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 nowhas really helped with innovation with other diseases.So for instance, a biotechnology companyhas now found broadly neutralizingantibodies 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 treatsevere, overwhelming cases of flu.In the longer term, what they can dois use these tools of retro-vaccinologyto make a preventive flu vaccine.Now, retro-vaccinology is just one techniquewithin 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 spotsalso 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 indicatethat such a vaccine could prevent severe disease,although you might get a mild case.So if this works in humans, what we're talking aboutis a universal flu vaccine,one that doesn't need to change every yearand would remove the threat of death.We really could think of flu, then,as just a bad cold.

Of course, the best vaccine imaginableis only valuable to the extentwe get it to everyone who needs it.So to do that, we have to combinesmart vaccine design with smart production methodsand, of course, smart delivery methods.So I want you to think back a few months ago.In June, the World Health Organizationdeclared the first globalflu pandemic in 41 years.The U.S. government promised150 million doses of vaccineby October 15th for the flu peak.Vaccines were promised to developing countries.Hundreds of millions of dollars were spentand flowed to accelerating vaccine manufacturing.So what happened?

Well, we first figured outhow to make flu vaccines, how to produce them,in the early 1940s.It was a slow, cumbersome processthat 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 dosesof vaccine per egg.Luckily for us,we live in an era of breathtakingbiomedical 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 reliablebut the problem is you never know how wella strain is going to grow.This year's swine flu straingrew 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 strainthat would infect the poultry flocks,and then we would have no eggs for our vaccines.So, Dan [Barber], if you wantbillions of chicken pellets for your fish farm,I know where to get them.So right now, the world can produceabout 350 million dosesof flu vaccine for the three strains,and we can up that to about 1.2 billion dosesif we want to target a single variantlike swine flu.But this assumes that our factories are hummingbecause, in 2004,the U.S. supply was cut in halfby contamination at one single plant.And the process still takesmore than half a year.

So are we better preparedthan we were in 1918?Well, with the new technologies emerging now,I hope we can say definitively, "Yes."Imagine we could produce enough flu vaccinefor everyone in the entire worldfor less than half of what we're currently spendingnow in the United States.With a range of new technologies, we could.Here's an example:A company I'm engaged with has founda specific piece of the H spike of fluthat sparks the immune system.If you lop this off and attach itto the tail of a different bacterium,which creates a vigorous immune response,they've created a very powerful flu fighter.This vaccine is so smallit 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 flufor 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 productionand 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 technologiesand they're leapfrogging the West.India, Mexico and others are alreadymaking experimental flu vaccines,and they may be the first placewe see these vaccines in use.Because these technologies are so efficientand relatively cheap,billions of people can have access to lifesaving vaccinesif we can figure out how to deliver them.

Now think of where this leads us.New infectious diseasesappear or reappearevery 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 reactbefore millions die?Luckily, this year's flu was relatively mild.I say, "luckily" in partbecause virtually no one in the developing worldwas vaccinated.So if we have the political and financial foresightto sustain our investments,we will master these and new tools of vaccinology,and with these tools we can produceenough vaccine for everyone at low costand ensure healthy productive lives.No longer must flu have to kill half a million people a year.No longer does AIDSneed to kill two million a year.No longer do the poor and vulnerableneed to be threatened by infectious diseases,or indeed, anybody.Instead of having Vaclav Smil's"massively fatal discontinuity" of life,we can ensurethe 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 scaleon, 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 iswe'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 issome 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 timelineon 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 iswe'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 technologiesbecause 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 outour 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 candidatethat actually showed efficacy in an earlier trialand 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)