The new science of personalized vaccines | Ofer Levy

Transcriber: Ivana Korom Reviewer: Krystian Aparta

譯者: Lilian Chiu 審譯者: Helen Chang

It is hard to overstate the beneficial effects of immunization.

免疫的好處是再怎麼 強調也不為過的。

According to the US Centers for Disease Control,

根據美國疾病管制與預防中心，

US children born over the last 20 years --

在過去二十年間 出生的美國兒童——

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

針對這些兒童，疫苗就能預防 至少三億兩千兩百萬次生病、

greater than 21 million hospitalizations

至少兩千一百萬次住院，

and greater than 730,000 deaths,

以及超過七十三萬人死亡，

with the societal cost savings of nearly 1.4 trillion dollars.

省下近一兆四千億美金的社會成本。

Those are big numbers.

這些數字很驚人。

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

但，咱們放大來看看 一個特別的例子。

Vaccines have nearly eliminated

疫苗幾乎消滅了一種細菌性感染：

a bacterial infection called Haemophilus influenzae.

流行性嗜血桿菌。

This bacterium used to infect young infants

以前，這種細菌會感染小嬰兒，

causing bloodstream infections,

造成血液感染、肺炎、腦膜炎、

pneumonia, meningitis, death

死亡，或永久性的殘疾。

or permanent disability.

As a young pediatrician, I saw a few cases.

當我還是年輕的小兒科醫生時 看過幾個案例。

You folks probably have never heard of this disease,

各位可能從來沒有聽過這種疾病，

because vaccines have been so effective.

因為疫苗相當有效。

You could see in the graph on the right

可以從右邊的圖上看到，

that since the introduction of vaccines,

從疫苗推出之後，

the incidence of Haemophilus bacterial infections

流行性嗜血桿菌的感染率

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

就像岩石掉落一樣，幾乎完全消失。

So vaccines are generally a success story.

疫苗的故事通常都是成功的故事。

But we also face challenges.

但，我們也會面臨挑戰。

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

比如，大部分的疫苗需要多劑

to achieve or maintain protection.

才能達到或維持保護效果。

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

科學圈一直在開發一劑奏效的疫苗。

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

想像你一生只需接種流感疫苗一次，

and not having to get a seasonal flu vaccine.

無需每季接種季節性的流感疫苗。

Certain microbes are difficult to immunize against.

我們很難對某些微生物免疫。

A classic example is human immunodeficiency virus, or HIV.

一個經典的例子就是 人體免疫缺損病毒（愛滋病病毒）。

The need is urgent, progress is being made;

這需求非常迫切，已經有所進展，

we're not there yet.

但我們還沒達成。

Another critical element in vaccine research right now

目前在疫苗研究中 還有另一個關鍵元素，

is optimizing vaccines for the most vulnerable among us,

就是為我們當中最虛弱的人， 將疫苗做到最好，

the very young and the elderly.

包括最小和最年長的人。

And this is an active area of research.

這是個很活躍的研究領域。

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

最後，我們不幸正面臨著的 最大挑戰之一

are anti-vax attitudes.

就是反對疫苗的態度。

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

事實上，這很讓人擔憂，

在美國有超過十萬名嬰兒和兒童

have not received any vaccines,

尚未接種任何疫苗，

and that number is growing.

且人數一直在增加。

In fact, the World Health Organization, or WHO,

事實上，世界衛生組織（WHO）

has declared anti-vax attitudes

已經公佈反對疫苗的態度

as one of the 10 most important threats to human health

是現今世界中

人類健康受到的前十大威脅之一。

in the world today.

This graphic illustrates the spread of anti-vax sentiment

這張圖所呈現的是反對疫苗的情節

在加州的分佈狀況，

in the state of California,

from the year 2000 to 2013,

時間是從 2000 年到 2013 年，

by looking at the percentage of public kindergarten students

計算的基礎是公立幼稚園中

who claim the personal exemption against immunization.

要求不要接種疫苗的學生比率。

Anti-vax sentiment is on the rise,

反對疫苗的情節正在攀升，

and it has very real consequences.

這會帶來很實在的後果。

Many of you may be aware of the fact

在座許多人可能知道，

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

已經開始有一些我們以為 早就解決掉的感染又重新出現。

coming back.

Measles outbreaks have been reported in multiple US states.

美國有不只一州接獲麻疹的通報。

And many have forgotten,

很多人已經忘了，

but measles is very infectious and dangerous.

但麻疹的感染性很強且很危險。

Just a few viral particles can infect an individual.

只要少數幾個病毒粒子 就足以感染人。

And there have been even reports

甚至有報告指出，

at sporting events and at an Olympic stadium

在運動比賽和奧林匹克體育館中，

where the virus, through the air, travels long distances

病毒透過空氣，傳播很遠的距離，

and infects a vulnerable person in the crowd.

感染到群眾中虛弱的人。

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

事實上，如果我得了 麻疹且現在咳嗽，

(Coughs)

（咳嗽）

somebody in the back of this auditorium could get infected.

在觀眾席後排的人 都有可能受到感染。

And this has had very real-world consequences.

這會產生非常現實的後果。

Just a few months ago,

幾個月前，

an airline stewardess contracted measles on a flight,

一名女空服員在飛機上得到麻疹，

the virus entered her brain and caused encephalitis,

病毒進入她的腦部，造成腦炎，

and she died.

她過世了。

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

現在有人因為這種 反對疫苗的情節而死。

I do want to take a few minutes

我真心想要花幾分鐘的時間， 對不相信疫苗的人

to address those who don't believe in vaccines

以及抗拒疫苗的人說幾句話。

and who resist vaccines.

As a pediatrician who receives my yearly flu vaccination,

因為我的身分包括每年接種 感冒疫苗的小兒科醫生、

as a parent of three children

一直都有根據建議時間表

who have been vaccinated according to the recommended schedule,

去接種疫苗的三個孩子的爸爸，

and as a pediatric infectious disease consultant

以及兒童感染性疾病顧問，

who has taken care of young children with meningitis

曾經照顧過腦膜炎病童，

that would have been preventable had their parents accepted immunization,

本來如果他們的父母願意 讓他們接種疫苗就可以避免染病，

this is a personal matter to me.

因此我視此為切身相關的事。

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

如果開始減少社會裡的疫苗接種，

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

看誰會付出代價。

This graph depicts, on the Y axis,

在這張圖上，Y 軸（縱軸）

the number of individuals dying of infection in the world.

代表世界上因為感染而死的人數。

And on the X axis,

X 軸（橫軸）

the age of the individuals who are dying.

則是死者的年齡。

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

各位可以看到， 分佈非常接近 U 字型，

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

年齡非常小的人數特別多。

So vaccines shield the very young from infection.

所以，疫苗能保護 年齡非常小的人不受感染。

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

各位朋友，若我們想要談 疫苗會造成什麼後果，

because there's a lot of speculation,

因為有很多揣測，

unfounded speculation on the internet, of what vaccines cause,

對於疫苗會造成什麼後果， 網路上有很多沒有基礎的揣測。

vaccines cause adults, OK?

疫苗讓兒童得以長大成人，了解嗎？

That's what they cause.

那是疫苗造成的結果。

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

疫苗還讓老年人更長壽。

Because they are shielded against influenza

因為疫苗能保護老人對抗

流感和其他老人殺手疾病。

and other killers of the elderly.

Now, let's talk a little bit

現在來談談如何進一步改善疫苗。

about how we can improve vaccines even further.

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

我們可以創造 讓我們當中最虛弱的人

也能具有免疫力的疫苗，

and perhaps even vaccines that protect with single shots.

甚至只要接種一次就能 產生保護作用的疫苗。

Let me go over a little bit of the immunology.

讓我幫大家簡單複習一下免疫學。

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

各位在上半部所看到的 是一種簡單的疫苗。

All vaccines contain something called an antigen.

所有的疫苗都含有所謂的「抗原」。

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

抗原就像是你的身體所記得的

that your body remembers, right?

病菌、微生物的一部分。

It forms antibodies and those antibodies can protect you.

它會形成抗體，而抗體會保護你。

So those kind of vaccines can induce an immune response,

所以，那些疫苗能誘發免疫反應，

but as you see here,

但，在這裡可以看到，

that immune response tends to go up and back down,

免疫反應通常會起起伏伏，

and you need to get another dose and another dose

你需要再接種一劑，然後再接種一劑，

to maintain protection.

才能維持保護作用。

What can we do?

我們能怎麼辦？

We and other scientists around the world

我們及世界各地的科學家

are finding molecules that can boost a vaccine response.

正在尋找能夠促進 疫苗反應的分子。

Those are called adjuvants,

它們被稱為「佐藥」，

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

來自拉丁字「adjuvare」， 意思是協助或幫助。

Adjuvants are molecules we might add to a vaccine

我們可以把這些被稱為佐藥的分子

加到疫苗中以造成更強的反應。

to get a stronger response.

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

這裡的紅色標記表示有用到佐藥，

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

有佐藥時，免疫細胞的白血球細胞

of your immune system,

會活化得比較完全，

and generate a much more profound immune response,

產生更完全的免疫反應，

with much higher antibody levels, more rapidly,

有更高的抗體濃度，速度也更快，

and that lasts a long time for durable immunity.

也會讓免疫能力更持久。

Interestingly, these adjuvants have different effects

有趣的是，這些佐藥對人的影響，

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

會因年齡或其他人口統計因子而異。

Which brings me to the notion of precision vaccines.

這就要談到「精準疫苗」的想法。

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

這個概念是把「精準醫學」——

you know what precision medicine is, right,

你們知道精準醫學是什麼吧，

that's the idea that populations may vary

它的概念就是人對於

in their response to a particular medicine --

某種藥的反應會有所不同——

and apply that to vaccines.

把這概念套到疫苗上。

Right?

對吧？

And here in Boston Children's Hospital

在波士頓兒童醫院這裡，

at the Precision Vaccines Program I direct,

在我主導的精準疫苗計畫中，

we have five approaches, stepwise approaches we take,

我們採用五個逐步式的方法，

to build precision vaccines

來打造精準疫苗，

that are tailored to vulnerable populations.

為較虛弱的族群來量身打造。

Number one,

第一，

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

我們得要了解某個目標族群 對於疫苗的態度是什麼。

towards a vaccine.

You could build the most sophisticated vaccine in the world,

你可以打造出世界上 最精密的疫苗，

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

但如果沒有人想接種，就沒有用。

Number two,

第二，我們得要思考 產生免疫力的途徑。

we have to think of the route of immunization.

Most vaccines are intramuscular, or IM,

大部分的疫苗是肌肉注射（IM），

but there are others, intranasal, oral and others.

但也有鼻內、口服， 及其他類型的疫苗。

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

我剛才有提過，疫苗有構成要素。

All vaccines have an antigen,

所有的疫苗都有抗原，

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

它是你的身體所記得的 微生物的一部分，

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

你可能會產生抗體或細胞介導免疫 來對抗這種微生物。

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

而我們可以像剛才提到的， 加入佐藥，來促進免疫反應。

to boost an immune response.

But guess what?

但你猜怎樣？

There are many different antigens to choose from

可選的抗原有很多種，佐藥也很多種。

and many different adjuvants.

How are we going to make that decision?

我們要怎麼選？

And the menu of these keeps growing.

且選項還不斷增加。

So on our team,

所以，我們的團隊已經開發出 在體外測試疫苗的方法——

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

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

拉丁文稱為「in vitro」——

in a tissue culture dish.

在組織培養皿裡面進行。

So we use tissue engineering with blood cells

我們把組織工程應用在血球細胞上，

to immunize outside the body

在體外產生免疫力，

and study the effect of the vaccine

研究疫苗對於

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

諸如嬰兒、老人或其他人的效果。

And if you think about it, this is critical,

仔細想想，這是很重要的，

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

因為如果探究我們想開發疫苗 來對抗的各種感染，

like Zika virus and Ebola virus and HIV and others,

比如茲卡病毒、伊波拉病毒、 愛滋病病毒，及其他，

all the candidate antigens,

有那麼多候選抗體，

all the candidate adjuvants,

有那麼多候選佐藥，

all the different populations,

有那麼多不同的族群，

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

不可能針對每種組合來做

大型的第三階段臨床試驗。

for every combination.

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

因此我們認為在體外測試疫苗

can make a big difference to accelerate vaccine development.

可以大大幫助加速疫苗開發。

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

最後，做這麼多努力的目的 是要促發免疫反應，

that will protect against that particular pathogen,

保護人體對抗某種病原體，

getting antibodies and other cells to defend the body.

讓抗體及其他細胞能夠悍衛人體。

We are also using additional innovative approaches

我們亦採用額外的創新方法，

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

把最先進的科學引入疫苗開發中。

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

我們正在更深入探究目前的疫苗 如何產生保護作用。

We've formed an international consortium

我們已經組成了一個國際同盟，

to study how hepatitis B vaccine protects newborns

來研究 B 型肝炎疫苗 如何保護新生兒

from hepatitis B infection.

不受 B 型肝炎感染。

And to do this,

為此，我們開發了一種技術， 叫做小樣本大資料。

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

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

在嬰兒產生免疫力之前， 我們可以取得嬰兒的一小滴血液，

and take a tiny little drop after immunization,

在產生免疫力之後再取一小滴，

and we can measure the inventory of all the cells,

接著，我們可以測量 那滴血液中的所有細胞、

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

所有基因，及所有分子，

and we can compare after the vaccine

針對同一個嬰兒，

to before the vaccine in that same baby

比較接種疫苗前後的差別，

and understand in a deep way

以深入了解

exactly how that successful vaccine protects.

該疫苗的保護作用有多成功。

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

我們所學到的，就可以 用在未來打造新的疫苗。

So this diagram is really illustrating a tiny drop of blood

這張圖所呈現出來的是一小滴血液

yielding huge amounts of information,

就能產生出大量的資訊，

tens of thousands of analytes,

數以萬計的被分析物，

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

那團毛球所描繪的是 被啟動的基因路徑

and the molecular pathways that are turned on.

以及被啟動的分子路徑。

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

這方面還有許多可期待的， 很讓人興奮的科學。

So we are partnering with scientists around the world

我們和世界各地的科學家合作，

to bring all these new technologies to invigorate vaccine development

導入各種新科技， 為精準疫苗網路的疫苗開發

in a Precision Vaccines network.

帶來新的可能性。

We are going to advance personalized vaccines

我們打算要為全世界虛弱的族群

for vulnerable populations around the world.

繼續發展個人化疫苗。

Our team includes scientists, technical experts and physicians.

我們的團隊成員有科學家、 技術專家，以及醫師。

And we're developing vaccines against infectious diseases

我們針對感染性疾病來開發疫苗，

like pertussis, which is whooping cough.

比如百日咳。

We have a whooping cough vaccine,

我們有百日咳疫苗，

but it requires multiple doses,

但需要不只一劑， 且免疫力會越來越低。

and the immunity keeps dropping.

We want to develop a single-shot pertussis vaccine.

我們想要開發出 只需一劑的百日咳疫苗。

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

我們也在致力開發 呼吸道融合病毒的疫苗，

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

在美國，造成嬰兒住院的 頭號原因就是這種病毒。

A better vaccine against influenza,

還有更好的流感疫苗，

and, of course, HIV.

當然，還有愛滋病。

We're also looking at vaccines against cancer, allergy

我們也在研究對抗 癌症、過敏的疫苗，

and, interestingly, opioid overdose.

很有趣的是還有對抗 鴉片過量的疫苗。

So, this is my final message to you.

接著是我要給各位的 最後一個訊息。

Vaccines protect you and your loved ones

疫苗能保護你、你所愛的人，

and the people around you.

及你周遭的人。

Not only do they protect you against infection,

疫苗不僅能保護你不受感染，

they prevent you from spreading it to others.

也能預防你將疾病散播給他人。

Get immunized.

去接種疫苗。

Scientific progress is fragile and can be lost.

科學進展很脆弱，易失去。

We must foster accurate and respectful public dialogue.

我們必須要讓大眾培養 正確且帶著尊重的討論對話。

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

最後，我們已經很接近

a new era of vaccination.

美妙的疫苗新紀元。

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

相對於能達成的成就， 我們現在只觸及皮毛而已。

Please advocate for this research.

請支持這項研究。

Thank you.

謝謝。

(Applause)

（掌聲）