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  • 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)

Transcriber: Ivana Korom Reviewer: Krystian Aparta

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B2 precision immune response response immune measles infection

The new science of personalized vaccines | Ofer Levy

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    林宜悉 posted on 2020/11/02
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