0:00:00.786,0:00:06.310
It is hard to overstate[br]the beneficial effects of immunization.

0:00:06.937,0:00:10.156
According to the US[br]Centers for Disease Control,

0:00:10.180,0:00:13.696
US children born over the last 20 years --

0:00:13.720,0:00:19.236
for those children, vaccines will prevent[br]greater than 322 million illnesses,

0:00:19.260,0:00:22.164
greater than 21 million hospitalizations

0:00:22.188,0:00:25.839
and greater than 730,000 deaths,

0:00:25.863,0:00:30.807
with the societal cost savings[br]of nearly 1.4 trillion dollars.

0:00:31.362,0:00:32.831
Those are big numbers.

0:00:32.855,0:00:35.406
But let's zoom in[br]and look at a particular example.

0:00:35.976,0:00:38.135
Vaccines have nearly eliminated

0:00:38.159,0:00:41.539
a bacterial infection[br]called Haemophilus influenzae.

0:00:41.563,0:00:44.826
This bacterium[br]used to infect young infants

0:00:44.850,0:00:46.379
causing bloodstream infections,

0:00:46.403,0:00:49.355
pneumonia, meningitis, death

0:00:49.379,0:00:50.979
or permanent disability.

0:00:51.585,0:00:54.696
As a young pediatrician,[br]I saw a few cases.

0:00:55.085,0:00:58.045
You folks probably have never[br]heard of this disease,

0:00:58.069,0:01:00.712
because vaccines have been so effective.

0:01:00.736,0:01:02.806
You could see in the graph on the right

0:01:02.830,0:01:04.997
that since the introduction of vaccines,

0:01:05.021,0:01:07.926
the incidence of Haemophilus[br]bacterial infections

0:01:07.950,0:01:11.386
has plummeted like a rock,[br]and it's nearly vanished.

0:01:12.180,0:01:14.736
So vaccines are generally a success story.

0:01:14.760,0:01:16.627
But we also face challenges.

0:01:17.069,0:01:21.240
For one, for most vaccines,[br]we need to give multiple doses

0:01:21.264,0:01:23.685
to achieve or maintain protection.

0:01:24.725,0:01:29.050
The scientific community is working[br]on developing single-shot vaccines.

0:01:29.074,0:01:32.832
Imagine being able to get only one[br]influenza shot your whole life

0:01:32.856,0:01:35.657
and not having to get[br]a seasonal flu vaccine.

0:01:36.197,0:01:39.943
Certain microbes[br]are difficult to immunize against.

0:01:39.967,0:01:44.191
A classic example is human[br]immunodeficiency virus, or HIV.

0:01:44.215,0:01:47.372
The need is urgent,[br]progress is being made;

0:01:47.396,0:01:48.572
we're not there yet.

0:01:49.588,0:01:53.069
Another critical element[br]in vaccine research right now

0:01:53.093,0:01:56.514
is optimizing vaccines[br]for the most vulnerable among us,

0:01:56.538,0:01:58.633
the very young and the elderly.

0:01:58.657,0:02:01.257
And this is an active area of research.

0:02:01.982,0:02:06.204
Finally, one of the biggest challenges[br]we unfortunately face right now

0:02:06.228,0:02:08.355
are anti-vax attitudes.

0:02:08.895,0:02:15.014
In fact, it's alarming that over 100,000[br]infants and children in the United States

0:02:15.038,0:02:16.998
have not received any vaccines,

0:02:17.022,0:02:18.822
and that number is growing.

0:02:19.180,0:02:22.545
In fact, the World Health[br]Organization, or WHO,

0:02:22.569,0:02:25.181
has declared anti-vax attitudes

0:02:25.205,0:02:29.403
as one of the 10 most important[br]threats to human health

0:02:29.427,0:02:31.022
in the world today.

0:02:31.046,0:02:35.410
This graphic illustrates[br]the spread of anti-vax sentiment

0:02:35.434,0:02:36.966
in the state of California,

0:02:36.990,0:02:40.022
from the year 2000 to 2013,

0:02:40.046,0:02:43.601
by looking at the percentage[br]of public kindergarten students

0:02:43.625,0:02:47.940
who claim the personal exemption[br]against immunization.

0:02:48.337,0:02:50.845
Anti-vax sentiment is on the rise,

0:02:50.869,0:02:53.257
and it has very real consequences.

0:02:53.281,0:02:55.355
Many of you may be aware of the fact

0:02:55.379,0:02:58.561
that we're seeing infections[br]that we thought we conquered long ago

0:02:58.585,0:02:59.736
coming back.

0:02:59.760,0:03:03.363
Measles outbreaks have been reported[br]in multiple US states.

0:03:03.387,0:03:04.783
And many have forgotten,

0:03:04.807,0:03:08.188
but measles is very[br]infectious and dangerous.

0:03:08.498,0:03:12.299
Just a few viral particles[br]can infect an individual.

0:03:12.743,0:03:14.815
And there have been even reports

0:03:14.839,0:03:17.259
at sporting events[br]and at an Olympic stadium

0:03:17.283,0:03:19.973
where the virus, through the air,[br]travels long distances

0:03:19.997,0:03:22.980
and infects a vulnerable[br]person in the crowd.

0:03:23.288,0:03:25.399
In fact, if I had[br]a measles cough right now,

0:03:25.423,0:03:26.580
(Coughs)

0:03:26.604,0:03:30.747
somebody in the back[br]of this auditorium could get infected.

0:03:31.903,0:03:35.268
And this has had[br]very real-world consequences.

0:03:35.292,0:03:36.482
Just a few months ago,

0:03:36.506,0:03:40.169
an airline stewardess[br]contracted measles on a flight,

0:03:40.193,0:03:43.264
the virus entered her brain[br]and caused encephalitis,

0:03:43.288,0:03:44.573
and she died.

0:03:44.597,0:03:48.145
So people are now dying[br]due to this anti-vax sentiment.

0:03:49.168,0:03:50.974
I do want to take a few minutes

0:03:50.998,0:03:53.443
to address those[br]who don't believe in vaccines

0:03:53.467,0:03:55.386
and who resist vaccines.

0:03:56.315,0:04:01.220
As a pediatrician who receives[br]my yearly flu vaccination,

0:04:01.244,0:04:03.297
as a parent of three children

0:04:03.321,0:04:07.612
who have been vaccinated according[br]to the recommended schedule,

0:04:07.636,0:04:10.413
and as a pediatric infectious[br]disease consultant

0:04:10.437,0:04:13.279
who has taken care[br]of young children with meningitis

0:04:13.303,0:04:17.156
that would have been preventable[br]had their parents accepted immunization,

0:04:17.180,0:04:19.101
this is a personal matter to me.

0:04:19.496,0:04:22.289
Let's take a look[br]at who is going to pay the price

0:04:22.313,0:04:26.336
if we start dialing back the amount[br]of vaccination in our society.

0:04:26.686,0:04:29.093
This graph depicts, on the Y axis,

0:04:29.117,0:04:32.561
the number of individuals[br]dying of infection in the world.

0:04:32.585,0:04:34.079
And on the X axis,

0:04:34.103,0:04:36.617
the age of the individuals who are dying.

0:04:36.641,0:04:40.061
And as you can see,[br]it's very much a U-shaped distribution,

0:04:40.085,0:04:43.291
and it's particularly stark[br]in the very young ages.

0:04:43.855,0:04:47.901
So vaccines shield[br]the very young from infection.

0:04:48.528,0:04:51.591
And if we want to talk, my friends,[br]about what vaccines cause,

0:04:51.615,0:04:53.385
because there's a lot of speculation,

0:04:53.409,0:04:57.014
unfounded speculation on the internet,[br]of what vaccines cause,

0:04:57.038,0:05:00.593
vaccines cause adults, OK?

0:05:00.617,0:05:01.783
That's what they cause.

0:05:01.807,0:05:06.713
And the other thing that they cause[br]is for elderly individuals to live longer.

0:05:06.737,0:05:09.137
Because they are shielded[br]against influenza

0:05:09.161,0:05:11.361
and other killers of the elderly.

0:05:12.340,0:05:13.729
Now, let's talk a little bit

0:05:13.753,0:05:16.204
about how we can improve[br]vaccines even further.

0:05:16.228,0:05:20.656
We can create vaccines that can immunize[br]the most vulnerable among us

0:05:20.680,0:05:24.045
and perhaps even vaccines[br]that protect with single shots.

0:05:24.363,0:05:26.879
Let me go over a little bit[br]of the immunology.

0:05:26.903,0:05:30.315
In the top panel, what you see[br]is a simple vaccine.

0:05:30.339,0:05:33.237
All vaccines contain[br]something called an antigen.

0:05:33.261,0:05:36.499
The antigen is like a piece[br]of a germ, of a microbe,

0:05:36.523,0:05:38.412
that your body remembers, right?

0:05:38.436,0:05:41.888
It forms antibodies[br]and those antibodies can protect you.

0:05:41.912,0:05:45.307
So those kind of vaccines[br]can induce an immune response,

0:05:45.331,0:05:46.664
but as you see here,

0:05:46.688,0:05:49.608
that immune response[br]tends to go up and back down,

0:05:49.632,0:05:52.339
and you need to get another dose[br]and another dose

0:05:52.363,0:05:54.172
to maintain protection.

0:05:54.196,0:05:55.346
What can we do?

0:05:55.836,0:05:58.011
We and other scientists around the world

0:05:58.035,0:06:01.336
are finding molecules[br]that can boost a vaccine response.

0:06:01.360,0:06:03.296
Those are called adjuvants,

0:06:03.320,0:06:06.212
from the Latin "adjuvare," to help or aid.

0:06:06.236,0:06:09.323
Adjuvants are molecules[br]we might add to a vaccine

0:06:09.347,0:06:11.045
to get a stronger response.

0:06:11.069,0:06:14.364
And in the presence of the adjuvant,[br]depicted here in red,

0:06:14.388,0:06:17.744
you have a much more profound[br]activation of the white blood cells

0:06:17.768,0:06:19.037
of your immune system,

0:06:19.061,0:06:21.950
and generate a much more[br]profound immune response,

0:06:21.974,0:06:24.735
with much higher antibody[br]levels, more rapidly,

0:06:24.759,0:06:27.775
and that lasts a long time[br]for durable immunity.

0:06:28.093,0:06:31.561
Interestingly, these adjuvants[br]have different effects

0:06:31.585,0:06:35.212
depending on the age or other demographic[br]factors of the individual.

0:06:35.665,0:06:38.861
Which brings me to the notion[br]of precision vaccines.

0:06:39.211,0:06:43.187
This is the idea that we will take[br]precision medicine --

0:06:43.211,0:06:45.227
you know what precision[br]medicine is, right,

0:06:45.251,0:06:47.775
that's the idea that populations may vary

0:06:47.799,0:06:50.244
in their response[br]to a particular medicine --

0:06:50.268,0:06:52.370
and apply that to vaccines.

0:06:52.784,0:06:53.934
Right?

0:06:53.958,0:06:56.142
And here in Boston Children's Hospital

0:06:56.166,0:06:58.775
at the Precision Vaccines[br]Program I direct,

0:06:58.799,0:07:02.061
we have five approaches,[br]stepwise approaches we take,

0:07:02.085,0:07:03.594
to build precision vaccines

0:07:03.618,0:07:06.466
that are tailored[br]to vulnerable populations.

0:07:06.490,0:07:07.727
Number one,

0:07:07.751,0:07:10.879
we need to understand[br]what the attitude of a given population is

0:07:10.903,0:07:12.063
towards a vaccine.

0:07:12.087,0:07:14.910
You could build the most[br]sophisticated vaccine in the world,

0:07:14.934,0:07:17.454
but if nobody wants to take it,[br]you're going nowhere.

0:07:17.759,0:07:18.910
Number two,

0:07:18.934,0:07:21.214
we have to think[br]of the route of immunization.

0:07:21.238,0:07:24.349
Most vaccines are intramuscular, or IM,

0:07:24.373,0:07:27.483
but there are others,[br]intranasal, oral and others.

0:07:28.142,0:07:31.363
Then, as I just described to you,[br]vaccines have components.

0:07:31.387,0:07:33.299
All vaccines have an antigen,

0:07:33.323,0:07:36.077
that's the part of the microbe[br]that your body remembers,

0:07:36.101,0:07:39.990
that you might make antibodies[br]or cell-mediated immunity against.

0:07:40.014,0:07:42.300
And we might add an adjuvant,[br]as we talked about,

0:07:42.324,0:07:43.918
to boost an immune response.

0:07:43.942,0:07:45.100
But guess what?

0:07:45.124,0:07:47.425
There are many different[br]antigens to choose from

0:07:47.449,0:07:48.839
and many different adjuvants.

0:07:48.863,0:07:50.728
How are we going to make that decision?

0:07:50.752,0:07:52.831
And the menu of these keeps growing.

0:07:52.855,0:07:54.006
So on our team,

0:07:54.030,0:07:57.514
we've developed ways[br]to test vaccines outside the body --

0:07:57.538,0:07:59.180
in Latin, that's "in vitro" --

0:07:59.204,0:08:00.823
in a tissue culture dish.

0:08:00.847,0:08:04.125
So we use tissue engineering[br]with blood cells

0:08:04.149,0:08:06.252
to immunize outside the body

0:08:06.276,0:08:08.332
and study the effect of the vaccine

0:08:08.356,0:08:12.696
against, for example, infants[br]or elderly individuals or others.

0:08:13.347,0:08:15.564
And if you think about it,[br]this is critical,

0:08:15.588,0:08:19.185
because if you look at all the infections[br]we want to build vaccines against,

0:08:19.209,0:08:23.170
like Zika virus and Ebola virus[br]and HIV and others,

0:08:23.194,0:08:24.988
all the candidate antigens,

0:08:25.012,0:08:27.115
all the candidate adjuvants,

0:08:27.139,0:08:29.115
all the different populations,

0:08:29.139,0:08:32.879
it's going to be impossible to do[br]large, phase III clinical trials

0:08:32.903,0:08:34.466
for every combination.

0:08:34.490,0:08:38.712
This is where we think being able[br]to test vaccines outside the body

0:08:38.736,0:08:42.187
can make a big difference[br]to accelerate vaccine development.

0:08:42.497,0:08:45.394
And finally, this whole effort[br]is to drive an immune response

0:08:45.418,0:08:48.671
that will protect against[br]that particular pathogen,

0:08:48.695,0:08:52.575
getting antibodies and other cells[br]to defend the body.

0:08:53.273,0:08:55.900
We are also using additional[br]innovative approaches

0:08:55.924,0:08:59.329
to bring the most cutting-edge science[br]to vaccine development.

0:08:59.353,0:09:03.450
We're taking a deeper dive[br]as to how current vaccines protect.

0:09:03.474,0:09:05.823
We've formed an international consortium

0:09:05.847,0:09:09.586
to study how hepatitis B vaccine[br]protects newborns

0:09:09.610,0:09:11.500
from hepatitis B infection.

0:09:11.524,0:09:12.675
And to do this,

0:09:12.699,0:09:16.103
we've developed a technique[br]called small sample, big data.

0:09:16.127,0:09:20.191
We can get a tiny little drop[br]of baby blood before immunization,

0:09:20.215,0:09:23.313
and take a tiny little drop[br]after immunization,

0:09:23.337,0:09:26.225
and we can measure the inventory[br]of all the cells,

0:09:26.249,0:09:29.615
and all the genes and all the molecules[br]in that drop of blood,

0:09:29.639,0:09:31.861
and we can compare after the vaccine

0:09:31.885,0:09:34.363
to before the vaccine in that same baby

0:09:34.387,0:09:36.252
and understand in a deep way

0:09:36.276,0:09:39.355
exactly how that successful[br]vaccine protects.

0:09:39.745,0:09:44.537
And those lessons we can use[br]to build the next vaccines in the future.

0:09:44.561,0:09:47.966
So this diagram is really illustrating[br]a tiny drop of blood

0:09:47.990,0:09:50.307
yielding huge amounts of information,

0:09:50.331,0:09:52.180
tens of thousands of analytes,

0:09:52.204,0:09:56.708
and that hairball is meant to depict[br]the gene pathways that are turned on

0:09:56.732,0:09:59.112
and the molecular pathways[br]that are turned on.

0:09:59.136,0:10:02.295
So much more to come on that,[br]and very exciting science.

0:10:02.660,0:10:05.700
So we are partnering[br]with scientists around the world

0:10:05.724,0:10:09.842
to bring all these new technologies[br]to invigorate vaccine development

0:10:09.866,0:10:11.921
in a Precision Vaccines network.

0:10:11.945,0:10:14.441
We are going to advance[br]personalized vaccines

0:10:14.465,0:10:17.017
for vulnerable populations[br]around the world.

0:10:17.041,0:10:21.923
Our team includes scientists,[br]technical experts and physicians.

0:10:21.947,0:10:24.749
And we're developing vaccines[br]against infectious diseases

0:10:24.773,0:10:27.177
like pertussis, which is whooping cough.

0:10:27.201,0:10:29.108
We have a whooping cough vaccine,

0:10:29.132,0:10:31.062
but it requires multiple doses,

0:10:31.086,0:10:32.617
and the immunity keeps dropping.

0:10:32.641,0:10:35.387
We want to develop a single-shot[br]pertussis vaccine.

0:10:35.411,0:10:38.315
We're working on a vaccine[br]for respiratory syncytial virus,

0:10:38.339,0:10:42.006
the number one cause of infant[br]hospitalization in the United States.

0:10:42.030,0:10:44.710
A better vaccine against influenza,

0:10:44.734,0:10:47.029
and, of course, HIV.

0:10:47.450,0:10:51.371
We're also looking at vaccines[br]against cancer, allergy

0:10:51.395,0:10:54.553
and, interestingly, opioid overdose.

0:10:55.815,0:10:58.609
So, this is my final message to you.

0:10:59.379,0:11:02.276
Vaccines protect you and your loved ones

0:11:02.300,0:11:03.712
and the people around you.

0:11:03.736,0:11:05.942
Not only do they protect you[br]against infection,

0:11:05.966,0:11:08.395
they prevent you[br]from spreading it to others.

0:11:08.419,0:11:09.815
Get immunized.

0:11:09.839,0:11:13.283
Scientific progress is fragile[br]and can be lost.

0:11:13.307,0:11:17.089
We must foster accurate[br]and respectful public dialogue.

0:11:17.427,0:11:19.688
And finally, we're on the verge[br]of great things,

0:11:19.712,0:11:21.841
a new era of vaccination.

0:11:21.865,0:11:24.825
We've just scratched the surface[br]of what can be accomplished.

0:11:24.849,0:11:26.834
Please advocate for this research.

0:11:26.858,0:11:28.039
Thank you.

0:11:28.063,0:11:30.951
(Applause)