pus from a cow and giving it to your wife and sons. Sure it was worth it to prevent

從一頭牛身上取下膿包，然後給你的妻子和兒子們吃。當然這是值得的，以防止

smallpox, but still...

天花，但仍然...

After the last year we've seen just how progressive we can be at developing a vaccine. Never before have we

經過去年，我們已經看到了我們在開發疫苗方面可以有多大的進步。以前我們從未

made one so efficiently, but COVID has done more than

如此高效地製作了一個，但COVID所做的工作超過了

just spark the development of COVID-specific vaccines, it has actually helped advance the

這只是引發了COVID特異性疫苗的開發，它實際上幫助推進了

entire industry in an unprecedented way.

整個行業以一種前所未有的方式發展。

Vaccinology has been a Field of Dreams that's been replete with innovation for the last

疫苗學一直是一個充滿創新的夢想領域，在過去的日子裡

225 years. And I think the COVID 19 pandemic that started more than a year ago has brought

225年。我認為一年多前開始的COVID 19大流行病已經帶來了

this to the fore. My name is Bali Pulendran, I am a professor of pathology and microbiology

這一點值得關注。我的名字是巴里-普倫德蘭，我是一名病理學和微生物學的教授

and immunology.

和免疫學。

When it comes to the future of vaccines, there are a lot of avenues that are making strides

談到疫苗的未來，有很多途徑正在取得進展

with things like mRNA vaccines, delivery systems, epigenetics, and universal vaccines... and spoiler

諸如mRNA疫苗、輸送系統、表觀遺傳學和通用疫苗......以及破壞者

alert, we're getting a lot closer to a certain type of universal vaccine than you may think.

警報，我們比你想象的更接近某種類型的通用疫苗。

Vaccinology is a discipline that is positioned at the focal point of immunology, virology

疫苗學是一門定位在免疫學、病毒學和生物技術之間的學科。

microbiology, public health, economics, sociology, ethics, and even international diplomacy.

微生物學、公共衛生、經濟學、社會學、倫理學，甚至是國際外交。

So when one thinks about the future of vaccines, one has to think about each of these elements,

是以，當人們思考疫苗的未來時，必須考慮到這些元素中的每一個。

the future of each of these elements.

這些要素中的每一個的未來。

One of the most exciting developments for the invention and distribution of vaccines

疫苗的發明和傳播最令人激動的發展之一是

is mRNA.

是mRNA。

mRNA vaccines is of course the new kid on the block, they've been extraordinarily efficacious

mRNA疫苗當然是這一領域的新生事物，它們已經有了超乎尋常的功效

in protecting against COVID-19. And the thing that everyone says is that these vaccines

在防止COVID-19方面。而大家都說的是，這些疫苗

were developed in such a short time, in a period of 11 months or so. But the important point

是在這麼短的時間內，在11個月左右的時間內發展起來的。但重要的一點是

to remember is that it's not as if we didn't know about the mRNA vaccines prior to the

需要記住的是，我們並不是不知道mRNA疫苗的存在。

emergence of COVID-19, there were teams of scientists working on this concept for years.

COVID-19的出現，有一些科學家團隊多年來一直在研究這個概念。

It just so happened that when COVID-19 emerged, they were rapidly able to pivot and to use

碰巧的是，當COVID-19出現時，他們能夠迅速地進行透視並使用

that technology, that investment that they had made over the last decade.

他們在過去十年裡所做的技術和投資。

mRNA or messenger RNA vaccines are such game changers because of how they're made, a traditional

mRNA或信使RNA疫苗之所以能改變遊戲規則，是因為它們的製作方式，傳統的

viral vaccine will deliver an inactivated, weakened or small piece of a virus to stimulate

病毒疫苗將提供一個滅活的、弱化的或小塊的病毒，以刺激

an immune response. But the neat thing about mRNA vaccines, is that they deliver the genetic

免疫反應。但是，關於mRNA疫苗的好處是，它們可以將遺傳基因傳遞給病人。

instructions directly to your cells, telling them exactly how to make the specific protein

直接向你的細胞發出指令，準確地告訴它們如何製造特定的蛋白質。

needed to generate that immune response. It's tapping into the way that mRNA typically helps

產生這種免疫反應所需的。它正在挖掘mRNA通常幫助的方式

cells to build, maintain and repair things in our bodies using proteins.

細胞利用蛋白質來建立、維護和修復我們體內的東西。

Now why this is so unique is that if you didn't have this mRNA technology, you would not have

現在，為什麼這是如此獨特的是，如果你沒有這種mRNA技術，你就不會有

access to our own cellular factories the so called ribosomes, we would be so dependent

如果我們能夠獲得我們自己的細胞工廠，即所謂的核糖體，我們將如此依賴

on manmade factories to produce these proteins and protein production is a whole new step

靠人造工廠來生產這些蛋白質，蛋白質的生產是一個全新的步驟。

and that can take a very long time several months perhaps a year or longer. So effectively

而這可能需要很長的時間，幾個月也許一年或更長。是以，有效地

what we've done is to bypass that entire protein production and use our body's own factories

我們所做的是繞過整個蛋白質生產，使用我們身體自身的工廠。

to our benefit.

對我們有利。

Right so mRNA means that you don't have to wait for all those proteins to be made, you

對，所以mRNA意味著你不必等待所有這些蛋白質被製造出來，你

can just teach cells, how to make it on their own. It's a teach a man to fish kind of thing,

就可以教細胞，如何自己做。這是一種授人以魚不如授人以漁的事情。

or like a teach a ribosome to mass produce a spike protein kind of thing. But even mRNA

或者像教一個核糖體大量生產穗狀蛋白的那種東西。但即使是mRNA

vaccines are limited in that they teach the immune system to respond specifically to one

疫苗的侷限性在於，它們教導免疫系統專門對一種疾病作出反應。

virus. So what if our vaccines didn't have to be so specialized per virus, or in the

病毒。那麼，如果我們的疫苗不必對每種病毒如此專門化，或者在

case of something like influenza, so specific to each variant of the virus, the development

在像流感這樣的情況下，每一種病毒的變體都有其特殊性，是以，發展

of a vaccine is predicated on the concept of teaching the immune system to recognize

疫苗的概念建立在教導免疫系統識別的基礎上

a very specific antigen, and priming cells that recognizes antigen in this case. Now,

一個非常具體的抗原，並在這種情況下給識別抗原的細胞打底。現在。

this is the concept on which vaccines are made immunological memory so that when this

這是一個概念，在此基礎上，疫苗被製成了免疫記憶，是以，當這

person encounters that particular pathogen decades afterwards, he or she has these memory

如果一個人在幾十年後遇到了那個特定的病原體，他或她就會有這些記憶

cells that recognize that pathogen and have the capacity to respond in a much more accelerated

識別該病原體並有能力以更快的速度作出反應的細胞。

manner and a much more invigorated or enhanced manner.

方式和更多的振奮或加強的方式。

But if we could pull everything we know about influenza viruses or the different kinds of

但是，如果我們能夠把我們所知道的關於流感病毒或不同種類的

coronaviruses and teach the immune system to look for more than just individual antigens,

冠狀病毒，並教導免疫系統不僅僅尋找個別抗原。

then we would bypass the need for these hyper specific vaccines. This vaccine would teach

那麼我們就會繞過這些超特異性疫苗的需求。這種疫苗將教導

the immune system to respond to anything that looks like a flu virus, even if it hasn't

免疫系統對任何看起來像流感病毒的東西作出反應，即使它還沒有

encountered its exact makeup before.

以前遇到過它的確切構成。

So I would say over the next five to 10 year frame and I think I'm being quite conservative.

所以我想說在未來5到10年的框架內，我認為我是相當保守的。

I wouldn't be surprised if we have something that looked like a universal influenza vaccine

如果我們有類似通用流感疫苗的東西，我也不會感到驚訝

that's ready for deployment. That's great,

已經準備好進行部署。這很好。

but let's zoom out even further. Are we at all close to a vaccine that would just fight

但讓我們進一步放大。我們是否已經接近一種疫苗，可以直接對抗

off anything? One shot to rule them all?

關閉任何東西？一槍定江山？

Within a few seconds of you getting your COVID vaccine shot your innate immune system is

在你注射COVID疫苗的幾秒鐘內，你的先天免疫系統就會

activated, and it teaches the T cells and the B cells to launch a vaccine response.

激活，並教導T細胞和B細胞發起疫苗反應。

Now, recent work over the last, I would say two or three years, suggests that the innate

現在，最近的工作，我想說的是，在過去的兩三年裡，表明先天的

immune system can have another role. It's not just a short-lived response that merely

免疫系統可以有另一個作用。它不僅僅是一種短暫的反應，只是

teaches the T and B cells to do their job, but it can also have a response that lasts

教導T和B細胞做他們的工作，但它也可以有一個持續的反應

a bit longer, not just a few days but perhaps a few weeks and maybe even a few months, and

再長一點，不只是幾天，也許是幾周，甚至是幾個月，而且

that response can actually fight off infections.

這種反應實際上可以抵禦感染。

And this is where it gets interesting. Instead of having to wait for your adaptive immune

這就是它變得有趣的地方。與其等待你的適應性免疫力

system that's those T and B cells to learn how to find and fight or virus, triggering

系統，讓那些T和B細胞學會如何尋找和對抗病毒，引發了

what are called epigenetic changes in the cells of the innate response could simply

先天性反應的細胞中所謂的表觀遺傳學變化可能只是

tell the immune system to kill a virus right away.

告訴免疫系統要立即殺死病毒。

So if you could deliver an adjuvant that could cause epigenetic imprinting and a heightened

是以，如果你能提供一種佐劑，可以引起表觀遺傳學印記和增強的

degree of resistance in the innate immune system for some period of time, perhaps, you

在先天性免疫系統中的抵抗程度在一段時間內，也許，你

know, a few weeks or maybe a few months, that would provide an effective sort of stopgap

知道，幾個星期或幾個月，這將提供一種有效的權宜之計。

measure that would confer a degree of protection against any virus that could emerge, then

採取措施，對可能出現的任何病毒提供一定程度的保護，然後

effectively you bridge that gap that critical window of time of a few months in which people

你可以有效地彌合這一差距，在這幾個月的關鍵時間窗口中，人們

are now being exposed to this virus but we don't have conventional vaccines.

現在正在接觸這種病毒，但我們沒有常規疫苗。

So in short, you'd be getting a vaccine that turbocharges the innate response via epigenetic

是以，簡而言之，你會得到一種疫苗，它通過表觀遺傳學為先天反應提供渦輪增壓。

imprinting to blast any virus that comes along, but that could be enough for us to keep a

印記，以炸燬任何出現的病毒，但這可能足以讓我們保持一個

disease at bay while we develop long term adaptive vaccines, when we have a mysterious

在我們開發長期的適應性疫苗時，當我們有一個神祕的

new virus going around. But while we wait for these turbo vaccines, those of us with

新的病毒正在四處蔓延。但在我們等待這些渦輪增壓疫苗的同時，我們這些擁有

trypanophobia, just want to know when we can get vaccines that don't require a needle,

錐體恐懼症，只想知道我們什麼時候能得到不需要打針的疫苗。

Are we

我們是否

always going to get an injection, or are there other types of vaccines? Well this is a question

總是去打針，還是有其他類型的疫苗？嗯，這是個問題

my 11 year old daughter asks me constantly, there are efforts underway to mucosal

我11歲的女兒不斷地問我，目前正在努力實現粘膜的 "無菌化"。

vaccines. These are vaccines that can be delivered orally, perhaps intranasally, and the great

疫苗。這些是可以口服的疫苗，也許是鼻內注射的疫苗，而大

advantage of mucosal vaccines, is that they could be administered, much more easily and these

粘膜疫苗的優點是，它們可以更容易地進行管理，這些

issues come into play in the developing world.

在發展中世界，這些問題開始發揮作用。