The new science of personalized vaccines | Ofer Levy

Transcriber: Ivana Korom Reviewer: Krystian Aparta

翻译人员: Wanting Zhong 校对人员: Yolanda Zhang

It is hard to overstate the beneficial effects of immunization.

免疫接种的益处 再怎么强调也不为过。

According to the US Centers for Disease Control,

根据美国疾病控制与预防中心的数据，

US children born over the last 20 years --

过去 20 年内出生的美国小孩——

for those children, vaccines will prevent greater than 322 million illnesses,

对他们来说，疫苗能预防 超过 3.22 亿起病例、

greater than 21 million hospitalizations

超过 2100 万例住院，

and greater than 730,000 deaths,

以及超过 73 万例死亡，

with the societal cost savings of nearly 1.4 trillion dollars.

并节省近 1 万 4 千亿美元的社会开支。

Those are big numbers.

这些都是巨额数字。

But let's zoom in and look at a particular example.

但让我们来具体看看一个实例。

Vaccines have nearly eliminated

疫苗已近乎根除了

a bacterial infection called Haemophilus influenzae.

一种叫做流感嗜血杆菌的细菌感染。

This bacterium used to infect young infants

在过去，这种细菌 会感染年幼的婴儿，

causing bloodstream infections,

导致血流感染、

pneumonia, meningitis, death

肺炎、脑膜炎、死亡

or permanent disability.

或者终身残疾。

As a young pediatrician, I saw a few cases.

当我还是一名年轻的儿科医生时， 我曾见过几个案例。

You folks probably have never heard of this disease,

大家可能从未听过这种疾病，

because vaccines have been so effective.

因为疫苗的效果非常好。

You could see in the graph on the right

从右边的图表里可以看出，

that since the introduction of vaccines,

自从引入了疫苗，

the incidence of Haemophilus bacterial infections

流感嗜血杆菌感染的病例

has plummeted like a rock, and it's nearly vanished.

呈断崖式骤降，并已几乎绝迹了。

So vaccines are generally a success story.

因此疫苗一般来说非常成功，

But we also face challenges.

但我们也面临着挑战。

For one, for most vaccines, we need to give multiple doses

首先，大多数疫苗需要多次接种

to achieve or maintain protection.

才能获得或维持免疫。

The scientific community is working on developing single-shot vaccines.

科学界正在努力开发 只需单次接种的疫苗。

Imagine being able to get only one influenza shot your whole life

试想一下，一辈子 只需要打一次流感疫苗，

and not having to get a seasonal flu vaccine.

再也不用去打季节性流感疫苗了。

Certain microbes are difficult to immunize against.

某些微生物导致的感染比较难预防。

A classic example is human immunodeficiency virus, or HIV.

一个经典例子就是人类免疫缺陷病毒， 即艾滋病毒（HIV）。

The need is urgent, progress is being made;

该疾病对疫苗的需求十分紧迫， 在研发方面也有所进展；

we're not there yet.

但还没有成功。

Another critical element in vaccine research right now

目前的疫苗研究中， 另一个至关重要的要素

is optimizing vaccines for the most vulnerable among us,

是为易感人群优化疫苗，

the very young and the elderly.

也就是婴幼儿和老年人。

And this is an active area of research.

这是一个非常活跃的研究领域。

Finally, one of the biggest challenges we unfortunately face right now

然而令人遗憾的是， 我们最终面临的最大挑战之一

are anti-vax attitudes.

是反对疫苗的态度。

In fact, it's alarming that over 100,000 infants and children in the United States

事实上，非常令人担忧的是， 美国有超过 10 万名婴儿与儿童

have not received any vaccines,

从未接种过任何疫苗，

and that number is growing.

而这个数字还在增长。

In fact, the World Health Organization, or WHO,

事实上，世界卫生组织（WHO）

has declared anti-vax attitudes

已经把反对疫苗的态度

as one of the 10 most important threats to human health

列为了当今世界上 对人类健康最重要的

in the world today.

十大威胁之一。

This graphic illustrates the spread of anti-vax sentiment

这张图诠释了 2000 年至 2013 年期间

in the state of California,

在加利福尼亚州

from the year 2000 to 2013,

扩散的反疫苗情绪，

by looking at the percentage of public kindergarten students

显示的是公共幼儿园学生中

who claim the personal exemption against immunization.

要求个人疫苗豁免的百分比。

Anti-vax sentiment is on the rise,

反疫苗情绪正在上升，

and it has very real consequences.

这会带来非常现实的后果。

Many of you may be aware of the fact

你们很多人可能都知道，

that we're seeing infections that we thought we conquered long ago

一些我们觉得很久以前 就已经消灭的传染病

coming back.

又开始死灰复燃了。

Measles outbreaks have been reported in multiple US states.

美国多个州都报道 出现了麻疹疫情。

And many have forgotten,

很多人已经遗忘了 这个严酷的事实：

but measles is very infectious and dangerous.

麻疹传染性极强，也很危险。

Just a few viral particles can infect an individual.

仅仅少量病毒颗粒 就能感染一个人。

And there have been even reports

甚至曾有报道称，

at sporting events and at an Olympic stadium

在体育比赛现场、 在奥运会场馆内，

where the virus, through the air, travels long distances

麻疹病毒在空气中 传播了很远的距离，

and infects a vulnerable person in the crowd.

并感染了人群中 一位易感人员。

In fact, if I had a measles cough right now,

事实上，如果我的咳嗽中 带有麻疹病毒，

(Coughs)

（咳嗽）

somebody in the back of this auditorium could get infected.

这个演讲厅后排的某个人 就可能会被传染。

And this has had very real-world consequences.

这一现象有着非常现实的后果。

Just a few months ago,

仅仅几个月前，

an airline stewardess contracted measles on a flight,

一位空姐在航班上感染了麻疹，

the virus entered her brain and caused encephalitis,

病毒进入了她的脑部， 引起了脑炎，

and she died.

导致她不幸去世。

So people are now dying due to this anti-vax sentiment.

现在人们正因为 这种反疫苗情绪而丧命。

I do want to take a few minutes

我想花几分钟时间，

to address those who don't believe in vaccines

跟那些不相信疫苗、 抵制疫苗的人

and who resist vaccines.

说几句话。

As a pediatrician who receives my yearly flu vaccination,

作为一名每年都接种 流感疫苗的儿科医生，

as a parent of three children

作为根据推荐时间表

who have been vaccinated according to the recommended schedule,

接种疫苗的三个孩子的家长，

and as a pediatric infectious disease consultant

作为一名照顾过脑膜炎患儿的

who has taken care of young children with meningitis

儿科传染病顾问——

that would have been preventable had their parents accepted immunization,

要是家长愿意为孩子接种疫苗， 他们完全可以不受病痛之苦——

this is a personal matter to me.

疫苗接种对于我个人 也有着非常重要的意义。

Let's take a look at who is going to pay the price

让我们看看，要是把社会中 疫苗接种的数量往回拨，

if we start dialing back the amount of vaccination in our society.

谁会为此付出代价。

This graph depicts, on the Y axis,

这张图的纵轴显示的

the number of individuals dying of infection in the world.

是世界上因感染而死亡的人数。

And on the X axis,

横轴则代表了

the age of the individuals who are dying.

死者的年龄。

And as you can see, it's very much a U-shaped distribution,

可以看出，这是一个 明显的“U”型分布，

and it's particularly stark in the very young ages.

在婴幼儿年龄段， 感染风险非常高，

So vaccines shield the very young from infection.

而疫苗能保护婴幼儿免受感染。

And if we want to talk, my friends, about what vaccines cause,

各位，如果我们想谈谈 疫苗会导致的后果，

because there's a lot of speculation,

因为有很多谣言——

unfounded speculation on the internet, of what vaccines cause,

网上对疫苗导致的后果 有很多毫无根据的流言——

vaccines cause adults, OK?

疫苗只会“导致”你长大成人，好吧？

That's what they cause.

这就是疫苗的后果。

And the other thing that they cause is for elderly individuals to live longer.

疫苗还能“导致”另一个后果， 那就是让老年人活得更长久。

Because they are shielded against influenza

因为它们能防护老年人 免受流感之恙，

and other killers of the elderly.

还有其他对老年人来说 非常致命的疾病。

Now, let's talk a little bit

那么，让我们再讲讲

about how we can improve vaccines even further.

如何进一步改良疫苗。

We can create vaccines that can immunize the most vulnerable among us

我们能研发出为最脆弱的人群 提供免疫保护的疫苗，

and perhaps even vaccines that protect with single shots.

或许甚至还能研发出 只需单次注射就能提供防护的疫苗。

Let me go over a little bit of the immunology.

让我简单介绍一下免疫学的原理。

In the top panel, what you see is a simple vaccine.

上面的图展示的 是一种简单的疫苗。

All vaccines contain something called an antigen.

所有疫苗都含有 一种叫做“抗原”的东西。

The antigen is like a piece of a germ, of a microbe,

抗原就像是一小块细菌， 一小块微生物，

that your body remembers, right?

能让你的身体记住它。

It forms antibodies and those antibodies can protect you.

你的身体会产生抗体， 而这些抗体能保护你。

So those kind of vaccines can induce an immune response,

这种疫苗能引起免疫反应。

but as you see here,

但像这里显示的这样，

that immune response tends to go up and back down,

免疫反应一般会先上升，随后回跌，

and you need to get another dose and another dose

于是你需要再接种一针又一针，

to maintain protection.

才能获得免疫保护。

What can we do?

我们能做些什么呢？

We and other scientists around the world

我们和世界各地的科学家

are finding molecules that can boost a vaccine response.

都在寻找能增强疫苗反应的分子。

Those are called adjuvants,

它们叫做 “佐剂（adjuvant）”，

from the Latin "adjuvare," to help or aid.

来源于拉丁语的 “adjuvare”， 意为 “帮助”，或 “协助”。

Adjuvants are molecules we might add to a vaccine

我们能把佐剂这种分子 添加到疫苗中，

to get a stronger response.

以增强免疫应答。

And in the presence of the adjuvant, depicted here in red,

在有佐剂，也就是图中的 红色星星的情况下，

you have a much more profound activation of the white blood cells

你的免疫系统中的白细胞

of your immune system,

会被更强烈地激活，

and generate a much more profound immune response,

产生更加强烈的免疫反应，

with much higher antibody levels, more rapidly,

更快地产生更高的抗体浓度，

and that lasts a long time for durable immunity.

并会持续更长时间， 提供持久的免疫保护。

Interestingly, these adjuvants have different effects

有趣的是，这些佐剂 会根据个体的年龄

depending on the age or other demographic factors of the individual.

或者其他人口学因素 产生不同的效果。

Which brings me to the notion of precision vaccines.

这也就引出了“精准疫苗”的概念。

This is the idea that we will take precision medicine --

这个概念是说， 我们能将精准医学——

you know what precision medicine is, right,

各位知道什么是精准医学吧，

that's the idea that populations may vary

就是指不同人群对某一特定药物

in their response to a particular medicine --

会产生不同反应——

and apply that to vaccines.

并将其应用到疫苗上。

Right?

对吧？

And here in Boston Children's Hospital

在波士顿儿童医院这里，

at the Precision Vaccines Program I direct,

在我负责的精准疫苗项目中，

we have five approaches, stepwise approaches we take,

我们会通过五种逐步式的方法

to build precision vaccines

为易感人群定制

that are tailored to vulnerable populations.

精准疫苗。

Number one,

第一，

we need to understand what the attitude of a given population is

我们需要理解某个特定群体

towards a vaccine.

对待疫苗的态度。

You could build the most sophisticated vaccine in the world,

你可以制作出世界上 最精良的疫苗，

but if nobody wants to take it, you're going nowhere.

但假如没有人愿意接种， 那还是徒劳。

Number two,

第二，

we have to think of the route of immunization.

我们必须考虑 免疫接种的途径。

Most vaccines are intramuscular, or IM,

大多数疫苗都是 通过肌肉注射接种的，

but there are others, intranasal, oral and others.

不过也有鼻内、口服等其它途径。

Then, as I just described to you, vaccines have components.

另外，就像我刚刚描述的那样， 疫苗有不同的组成成分。

All vaccines have an antigen,

所有疫苗都含有抗原，

that's the part of the microbe that your body remembers,

也就是你的身体所记住的 微生物的一部分，

that you might make antibodies or cell-mediated immunity against.

你能对它产生抗体 或者细胞介导免疫反应。

And we might add an adjuvant, as we talked about,

此外，我还提到过， 我们可以添加佐剂，

to boost an immune response.

以增强免疫反应。

But guess what?

猜猜看怎么着？

There are many different antigens to choose from

我们可以从很多不同抗原

和很多不同佐剂中进行选择。

and many different adjuvants.

How are we going to make that decision?

我们该如何做出决定呢？

And the menu of these keeps growing.

而这些成分的种类 还在不断增长。

So on our team,

于是我们的团队

we've developed ways to test vaccines outside the body --

开发了在组织培养皿中，

即在体外测试疫苗的方法——

in Latin, that's "in vitro" --

in a tissue culture dish.

拉丁文叫做 “in vitro”。

So we use tissue engineering with blood cells

我们对血细胞进行组织工程学处理，

to immunize outside the body

在体外接种疫苗，

and study the effect of the vaccine

并研究疫苗对婴儿、

against, for example, infants or elderly individuals or others.

老年人或其他人群的效果。

And if you think about it, this is critical,

仔细想想就会发现 这一步至关重要，

because if you look at all the infections we want to build vaccines against,

因为如果考虑到我们想要 通过疫苗预防的所有传染病，

like Zika virus and Ebola virus and HIV and others,

比如寨卡病毒、埃博拉病毒、 艾滋病毒等等，

all the candidate antigens,

所有待选病原体、

all the candidate adjuvants,

所有待选佐剂、

all the different populations,

所有不同人群，

it's going to be impossible to do large, phase III clinical trials

我们不可能对每一种组合都进行

for every combination.

大型 Ⅲ 期临床试验。

This is where we think being able to test vaccines outside the body

因此我们认为， 在体外测试疫苗

can make a big difference to accelerate vaccine development.

能够大大加速疫苗的研发。

And finally, this whole effort is to drive an immune response

最后，所有这些努力 都是为了激活免疫反应，

that will protect against that particular pathogen,

针对某种特定病原体构筑防线，

getting antibodies and other cells to defend the body.

让抗体和其它细胞 为身体进行防御。

We are also using additional innovative approaches

我们还在使用其它创新的方法，

to bring the most cutting-edge science to vaccine development.

将最前沿的科技 引入疫苗研发中。

We're taking a deeper dive as to how current vaccines protect.

我们还在深入研究 目前的疫苗究竟如何提供防护。

We've formed an international consortium

我们形成了一个国际联合会，

to study how hepatitis B vaccine protects newborns

研究乙肝疫苗如何保护新生儿

from hepatitis B infection.

免遭乙肝病毒感染。

And to do this,

为了实现这一目标，

we've developed a technique called small sample, big data.

我们开发了一项称为 “小样本，大数据”的技术。

We can get a tiny little drop of baby blood before immunization,

我们可以在接种疫苗之前以及之后

and take a tiny little drop after immunization,

各采集一小滴婴儿的血液样本，

and we can measure the inventory of all the cells,

然后我们就能测量那一小滴血里

and all the genes and all the molecules in that drop of blood,

所有的细胞、基因和分子，

and we can compare after the vaccine

于是我们就能比较同一个婴儿

to before the vaccine in that same baby

接种疫苗前后的数据，

and understand in a deep way

从更深的层面理解

exactly how that successful vaccine protects.

那个成功的疫苗 究竟是如何提供保护的。

And those lessons we can use to build the next vaccines in the future.

然后我们就能将这些知识 应用到未来的疫苗研发中去。

So this diagram is really illustrating a tiny drop of blood

这张图展示了一小滴血

yielding huge amounts of information,

蕴含了海量信息，

tens of thousands of analytes,

成千上万种分析物，

and that hairball is meant to depict the gene pathways that are turned on

那边的“线团”描述的是 被启动的基因回路

and the molecular pathways that are turned on.

和被激活的分子通路。

So much more to come on that, and very exciting science.

这是一项十分激动人心的科学， 我们将迎来很多重大进展。

So we are partnering with scientists around the world

目前，我们在和 世界各地的科学家合作，

to bring all these new technologies to invigorate vaccine development

通过一个“精准疫苗网络”

来汇聚这些新科技 以推动疫苗研发。

in a Precision Vaccines network.

We are going to advance personalized vaccines

我们将为了世界各地的易感人群

for vulnerable populations around the world.

推进个性化疫苗研究。

Our team includes scientists, technical experts and physicians.

我们的团队成员有科学家、 技术专家和医师。

And we're developing vaccines against infectious diseases

我们还在为百日咳

like pertussis, which is whooping cough.

这样的传染病研发疫苗。

We have a whooping cough vaccine,

我们已经有了百日咳疫苗，

but it requires multiple doses,

但目前还需要多次接种，

and the immunity keeps dropping.

而且免疫效果会持续下降。

We want to develop a single-shot pertussis vaccine.

我们想要研制一种只需 单次接种的百日咳疫苗。

We're working on a vaccine for respiratory syncytial virus,

我们也在研发一种预防 呼吸道合胞病毒的疫苗，

the number one cause of infant hospitalization in the United States.

在美国，这是导致 婴儿住院的头号原因。

A better vaccine against influenza,

我们还在开发更好的流感疫苗，

and, of course, HIV.

当然还有艾滋病疫苗。

We're also looking at vaccines against cancer, allergy

同时，我们也在研究 针对癌症和过敏的疫苗，

and, interestingly, opioid overdose.

还有一个有意思的， 预防阿片类药物摄入过量的疫苗。

So, this is my final message to you.

那么，最后我想对大家说：

Vaccines protect you and your loved ones

疫苗能保护你、你心爱的人，

and the people around you.

还有你身边的人们。

Not only do they protect you against infection,

它们不仅能保护你免受感染，

they prevent you from spreading it to others.

还能防止你把疾病传播给别人。

Get immunized.

去接种疫苗吧。

Scientific progress is fragile and can be lost.

科学进步是脆弱的， 随时可能会遗失。

We must foster accurate and respectful public dialogue.

我们必须培养准确的、 互相尊重的公共对话。

And finally, we're on the verge of great things,

最后我要说的是， 我们正在迈入伟大的

a new era of vaccination.

疫苗新时代，

We've just scratched the surface of what can be accomplished.

而目前还仅仅触及了冰山一角。

Please advocate for this research.

请各位鼎力支持这类研究。

Thank you.

谢谢。

(Applause)

（掌声）