The new science of personalized vaccines Ofer Levy
Transcriber: Ivana Korom
Reviewer: Krystian Aparta
It is hard to overstate
the beneficial effects of immunization.
According to the US
Centers for Disease Control,
US children born over the last 20 years –
for those children, vaccines will prevent
greater than 322 million illnesses,
greater than 21 million hospitalizations
and greater than 730,000 deaths,
with the societal cost savings
of nearly 1.4 trillion dollars.
Those are big numbers.
But let’s zoom in
and look at a particular example.
Vaccines have nearly eliminated
a bacterial infection
called Haemophilus influenzae.
This bacterium
used to infect young infants
causing bloodstream infections,
pneumonia, meningitis, death
or permanent disability.
As a young pediatrician,
I saw a few cases.
You folks probably have never
heard of this disease,
because vaccines have been so effective.
You could see in the graph on the right
that since the introduction of vaccines,
the incidence of Haemophilus
bacterial infections
has plummeted like a rock,
and it’s nearly vanished.
So vaccines are generally a success story.
But we also face challenges.
For one, for most vaccines,
we need to give multiple doses
to achieve or maintain protection.
The scientific community is working
on developing single-shot vaccines.
Imagine being able to get only one
influenza shot your whole life
and not having to get
a seasonal flu vaccine.
Certain microbes
are difficult to immunize against.
A classic example is human
immunodeficiency virus, or HIV.
The need is urgent,
progress is being made;
we’re not there yet.
Another critical element
in vaccine research right now
is optimizing vaccines
for the most vulnerable among us,
the very young and the elderly.
And this is an active area of research.
Finally, one of the biggest challenges
we unfortunately face right now
are anti-vax attitudes.
In fact, it’s alarming that over 100,000
infants and children in the United States
have not received any vaccines,
and that number is growing.
In fact, the World Health
Organization, or WHO,
has declared anti-vax attitudes
as one of the 10 most important
threats to human health
in the world today.
This graphic illustrates
the spread of anti-vax sentiment
in the state of California,
from the year 2000 to 2013,
by looking at the percentage
of public kindergarten students
who claim the personal exemption
against immunization.
Anti-vax sentiment is on the rise,
and it has very real consequences.
Many of you may be aware of the fact
that we’re seeing infections
that we thought we conquered long ago
coming back.
Measles outbreaks have been reported
in multiple US states.
And many have forgotten,
but measles is very
infectious and dangerous.
Just a few viral particles
can infect an individual.
And there have been even reports
at sporting events
and at an Olympic stadium
where the virus, through the air,
travels long distances
and infects a vulnerable
person in the crowd.
In fact, if I had
a measles cough right now,
(Coughs)
somebody in the back
of this auditorium could get infected.
And this has had
very real-world consequences.
Just a few months ago,
an airline stewardess
contracted measles on a flight,
the virus entered her brain
and caused encephalitis,
and she died.
So people are now dying
due to this anti-vax sentiment.
I do want to take a few minutes
to address those
who don’t believe in vaccines
and who resist vaccines.
As a pediatrician who receives
my yearly flu vaccination,
as a parent of three children
who have been vaccinated according
to the recommended schedule,
and as a pediatric infectious
disease consultant
who has taken care
of young children with meningitis
that would have been preventable
had their parents accepted immunization,
this is a personal matter to me.
Let’s take a look
at who is going to pay the price
if we start dialing back the amount
of vaccination in our society.
This graph depicts, on the Y axis,
the number of individuals
dying of infection in the world.
And on the X axis,
the age of the individuals who are dying.
And as you can see,
it’s very much a U-shaped distribution,
and it’s particularly stark
in the very young ages.
So vaccines shield
the very young from infection.
And if we want to talk, my friends,
about what vaccines cause,
because there’s a lot of speculation,
unfounded speculation on the internet,
of what vaccines cause,
vaccines cause adults, OK?
That’s what they cause.
And the other thing that they cause
is for elderly individuals to live longer.
Because they are shielded
against influenza
and other killers of the elderly.
Now, let’s talk a little bit
about how we can improve
vaccines even further.
We can create vaccines that can immunize
the most vulnerable among us
and perhaps even vaccines
that protect with single shots.
Let me go over a little bit
of the immunology.
In the top panel, what you see
is a simple vaccine.
All vaccines contain
something called an antigen.
The antigen is like a piece
of a germ, of a microbe,
that your body remembers, right?
It forms antibodies
and those antibodies can protect you.
So those kind of vaccines
can induce an immune response,
but as you see here,
that immune response
tends to go up and back down,
and you need to get another dose
and another dose
to maintain protection.
What can we do?
We and other scientists around the world
are finding molecules
that can boost a vaccine response.
Those are called adjuvants,
from the Latin “adjuvare,” to help or aid.
Adjuvants are molecules
we might add to a vaccine
to get a stronger response.
And in the presence of the adjuvant,
depicted here in red,
you have a much more profound
activation of the white blood cells
of your immune system,
and generate a much more
profound immune response,
with much higher antibody
levels, more rapidly,
and that lasts a long time
for durable immunity.
Interestingly, these adjuvants
have different effects
depending on the age or other demographic
factors of the individual.
Which brings me to the notion
of precision vaccines.
This is the idea that we will take
precision medicine –
you know what precision
medicine is, right,
that’s the idea that populations may vary
in their response
to a particular medicine –
and apply that to vaccines.
Right?
And here in Boston Children’s Hospital
at the Precision Vaccines
Program I direct,
we have five approaches,
stepwise approaches we take,
to build precision vaccines
that are tailored
to vulnerable populations.
Number one,
we need to understand
what the attitude of a given population is
towards a vaccine.
You could build the most
sophisticated vaccine in the world,
but if nobody wants to take it,
you’re going nowhere.
Number two,
we have to think
of the route of immunization.
Most vaccines are intramuscular, or IM,
but there are others,
intranasal, oral and others.
Then, as I just described to you,
vaccines have components.
All vaccines have an antigen,
that’s the part of the microbe
that your body remembers,
that you might make antibodies
or cell-mediated immunity against.
And we might add an adjuvant,
as we talked about,
to boost an immune response.
But guess what?
There are many different
antigens to choose from
and many different adjuvants.
How are we going to make that decision?
And the menu of these keeps growing.
So on our team,
we’ve developed ways
to test vaccines outside the body –
in Latin, that’s “in vitro” –
in a tissue culture dish.
So we use tissue engineering
with blood cells
to immunize outside the body
and study the effect of the vaccine
against, for example, infants
or elderly individuals or others.
And if you think about it,
this is critical,
because if you look at all the infections
we want to build vaccines against,
like Zika virus and Ebola virus
and HIV and others,
all the candidate antigens,
all the candidate adjuvants,
all the different populations,
it’s going to be impossible to do
large, phase III clinical trials
for every combination.
This is where we think being able
to test vaccines outside the body
can make a big difference
to accelerate vaccine development.
And finally, this whole effort
is to drive an immune response
that will protect against
that particular pathogen,
getting antibodies and other cells
to defend the body.
We are also using additional
innovative approaches
to bring the most cutting-edge science
to vaccine development.
We’re taking a deeper dive
as to how current vaccines protect.
We’ve formed an international consortium
to study how hepatitis B vaccine
protects newborns
from hepatitis B infection.
And to do this,
we’ve developed a technique
called small sample, big data.
We can get a tiny little drop
of baby blood before immunization,
and take a tiny little drop
after immunization,
and we can measure the inventory
of all the cells,
and all the genes and all the molecules
in that drop of blood,
and we can compare after the vaccine
to before the vaccine in that same baby
and understand in a deep way
exactly how that successful
vaccine protects.
And those lessons we can use
to build the next vaccines in the future.
So this diagram is really illustrating
a tiny drop of blood
yielding huge amounts of information,
tens of thousands of analytes,
and that hairball is meant to depict
the gene pathways that are turned on
and the molecular pathways
that are turned on.
So much more to come on that,
and very exciting science.
So we are partnering
with scientists around the world
to bring all these new technologies
to invigorate vaccine development
in a Precision Vaccines network.
We are going to advance
personalized vaccines
for vulnerable populations
around the world.
Our team includes scientists,
technical experts and physicians.
And we’re developing vaccines
against infectious diseases
like pertussis, which is whooping cough.
We have a whooping cough vaccine,
but it requires multiple doses,
and the immunity keeps dropping.
We want to develop a single-shot
pertussis vaccine.
We’re working on a vaccine
for respiratory syncytial virus,
the number one cause of infant
hospitalization in the United States.
A better vaccine against influenza,
and, of course, HIV.
We’re also looking at vaccines
against cancer, allergy
and, interestingly, opioid overdose.
So, this is my final message to you.
Vaccines protect you and your loved ones
and the people around you.
Not only do they protect you
against infection,
they prevent you
from spreading it to others.
Get immunized.
Scientific progress is fragile
and can be lost.
We must foster accurate
and respectful public dialogue.
And finally, we’re on the verge
of great things,
a new era of vaccination.
We’ve just scratched the surface
of what can be accomplished.
Please advocate for this research.
Thank you.
(Applause)