An HIV vaccine is what the world needs now

[Music]

i’m a laboratory-based scientist

and for the last 25 years of my career

i’ve been trying to make a vaccine to

hiv

and now we have three vaccines for

covert

in less than a year how did this happen

well the covet vaccines benefited a lot

from the the years of investment

in hiv vaccines and what i want to tell

you about today

is how we can use that momentum to speed

up the development

of an hiv vaccine but first let’s look

at these two viruses

they certainly have some similarities as

you can see they are small microscopic

viruses and you need very powerful

microscopes to see them

but there’s also some significant

differences so

sar’s curvy ii which is the virus that

causes covet 19

is spread via the respiratory root so

that’s simply breathing

and it means that everybody is

susceptible this virus causes an acute

infection

that means it’s very short-lived and the

body is able to clear the virus

and as we know most that happens in most

people

and that’s because our bodies make an

immune response to the virus

particularly neutralizing antibodies

which develop in almost

everybody another important feature is

that this virus

is very stable so the 60 million people

around the world that have been

infected with this virus are infected

with a very related virus

there are some differences but it is

very similar

now hiv in contrast causes a chronic

infection

and that means it it’s it’s a lifelong

infection

and that’s because this virus integrates

into

our genetic material into our dna

the other major factor is that the

neutralizing antibody response here is

very slow and ineffective and then

another major

hurdle for hiv vaccine development is

the virus mutates and it really is a

moving target

now vaccines have been one of our most

successful ways of dealing with

infectious diseases

and most vaccines work by in inducing

neutralizing antibodies these are part

of our immune response

and neutralizing antibodies work because

they

specifically bind to parts of the virus

in this case it’s the spike protein

which surrounds the

um the sars cov2 particle

so it’s actually a physical interaction

the the antibody

binds to the spike and stops the virus

from infecting cells and that’s what it

means by

uh by neutralizing so let’s have a

closer look at this

sars covi2 protein so this is what

causes the spikes or the corona around

the virus

and scientists have been able to

look at this at what’s called a very

high resolution and in fact

again it’s hiv scientists who turned

their attention

to looking at the sars curvy ii

protein partly that’s because of the

urgency but also because a lot of

funding was made available

for people to study covert 19. but

what we what we’ve learned from from the

structure

of the spike protein is that the the

part that’s targeted by the antibodies

is a very focused part that’s the part

that’s colored in

in red and so that is the major target

that we’re looking

because that is the part of the protein

that binds

to the cells now

a number of different vaccines have been

made against covet 19

and again it’s really benefited from the

vaccine development that’s been taking

place for for decades

with hiv and so this just shows you some

of the different approaches that have

been taken

and many of you will know i think then

our household names some of these uh

these vaccine manufacturers so the

genetic vaccines which are

composed of the rna or the dna

of the virus of the spike protein are

used to stimulate an immune response

these same genes are also put into what

is called a viral vector

so it’s a harmless virus to actually

carry these genes into the body

almost like a trojan horse so in these

kinds of vaccines

the body is in fact making the spike

protein

we’re actually making our own vaccine in

a way

the third kind of vaccine is called a

protein vaccine

and this is where we make the protein in

the laboratory and then

you know use that to immunize people and

this is a much more traditional

approach to vaccine development and it

it’s it’s it takes a lot longer and is

actually much more expensive

so there’s certainly and it’s been

widely reported in the media

about you know this incredible effort to

develop

a covert vaccine and now we know we

already have three

that have shown that they work that they

have a high level of efficacy

the two rna vaccines were shown to have

over 90

efficacy and the vectored vaccine

was also had very good efficacy but as

you can see from what’s called this

pipeline

there are another 10 that are still

undergoing testing and certainly are um

you know we we suspect that they’re also

going to work

and you can see that in the earlier

phases of of testing there are a large

number of vaccines so we have a very

very robust pipeline

for covert vaccine development and

although none have been licensed as yet

that is also very very imminent

in contrast in the 20 years

of doing hiv vaccine trials we’ve only

ever done

six efficacy trials um in the in in 20

years so

just to give you a sense of uh you know

the difference uh

and how we’re tackling these two viruses

but i don’t want to make it sound as if

hiv vaccine development is easy because

it isn’t it’s actually one of the

biggest challenges of our time

and that’s really because this virus

does change

so we the laboratory that

that i run at the at the at the nicd

has been looking at how to develop these

broadly neutralizing antibodies in

infected people

and we discovered during this process

that the virus

is changing to create the kinds of

stimuli that you need to to get the

right kinds of antibodies

and so this this evolutionary process

is now being incorporated into vaccine

design

and so the the the paradigm is is that

we’ll need to have different

different vaccines in order to shepherd

the antibody response along so it can

become

a neutralizing antibody response and

that’s just shown graphically here

um so the um this is the

the the equivalent of the spike protein

in hiv is called the envelope protein

and so each of those different colors

shows that it’s a slightly different

envelope protein

in order to to basically as i say coax

the immune response along the right

pathway to make neutralizing antibodies

so certainly in terms of vaccine

development you know hiv presents

you know some significant challenges so

i

am participated in a covert vaccine

trial

the novovax trial that’s been run by

this university

and i did that because i really believe

in vaccines i believe in the power of

vaccines

and also because i am vulnerable just

like everybody else to

you know to being infected by sales

curvy 2.

and so i had two vaccinations

and you know i sort of imagined this uh

protein circulating in my body and my

b cells trying to you know hunt it down

so it could

produce the right kinds of antibodies in

order to you know to protect me

um and uh you know during this time one

kept one keeps a vaccine diary

you keep track of your um you know your

temperatures where there’s any swelling

or redness

and there really was very minor uh

pretty similar to an insect bite

that really resolved within a few days

um

of course i don’t know yet if i’m on the

placebo or the active arm of the

of the vaccine that will only be be

found out later

and that’s really a critical thing for

um

you know for determining how a vaccine

works is to measure the immune responses

in people who’ve been vaccinated

and to determine what’s called the

correlate of protection so we need to

know what levels of antibodies

the vaccine needs to stimulate in order

to protect people from infection and

that’s what these trials are going to

show

so a very critical thing and in fact

once we have the correlate of protection

actually the vaccine development process

is going to speed up even further

but i also you know like you know we’ve

been learning as we go

with this epidemic that we still have

many unknowns

so we don’t know how long immunity is

going to last we don’t know if these

vaccines are going to work for everybody

um though there’s certainly good signs

that they do work in older people who of

course are a major target group

um we’re not sure if we’re measuring

exactly the right immune responses

um because there may be other things

that we

you know are still to discover and i

think a very critical thing is um

you know will the virus change in the

same way that it changes with hiv

and represent a problem you know once

the a number of people

um have immunity to sars it’s going to

put pressure on the virus and so that is

one of the things that we certainly need

to keep

track of so now i want to look at the

global devastation caused by these two

epidemics so the top

graph shows the number of deaths caused

by sars kovi ii per week

since the start of the outbreak and what

you can see is in the purple is the

first wave that occurred in europe and

you can see the resurgence now that’s

happening

and then you can see the high level

and ongoing uh level of deaths in the

americas

and what is most um disturbing about

this graph

is that these the resurgence levels are

higher than the initial levels

and really speaks to our the urgent need

to start deploying these

um active these efficacious vaccines

because if we don’t um these waves will

keep happening

this virus will become endemic and it

will keep spreading amongst susceptible

people so so far

in 11 months 1.4 million people have

died of covet 19

and we certainly don’t want to be

getting to the levels that we see with

hiv

of 35 million people so

the reason why there’s 35 million people

who have died from hiv is because hiv

has been with us for a very long time

and as you know we don’t have a vaccine

but what we do have is we do have good

antiretroviral therapies

and you can see the effect of those on

on the graph below

so at the peak of the aids epidemic

approximately 1.6 million people were

dying per year

and that decline was when antiretroviral

therapy started being widely used

but we it’s not going to get us to zero

because antiretroviral therapy treats

infected people what we need

is we need to prevent people from

getting infected and that’s why we need

a vaccine

so we need that vaccine to get that

curve right down

just last year 2019 over 700 000 people

died of hiv so the other important thing

about this graph

is the colors so you can see that

that it’s mostly red and that’s because

hiv

is mostly affects the african continent

but it also we also know historically

that

vaccine development or africa has been

very neglected in terms of developing

vaccines for diseases

that affect the african continent

so what can we learn from covet 19 that

will help us to develop

an hiv vaccine more rapidly so

what we need to be doing is testing

developing and testing multiple

candidates

we need a robust pipeline the same way

that we’re doing with covert we need to

be testing lots of different concepts

um testing them all at the same time we

certainly need to be testing the mrna

vaccines

um which were originally developed for

hiv but you know now are being tested

for covert we need to go back

and we need to be doing that we also

need to run parallel processes so while

we’re testing we need to be

manufacturing and we need to be seeking

approvals

it’s high risk but it’s

it’s it’s it fast tracks the process and

we certainly need more money

so covert 19 the amount of money spent

on covert 19 is 8 to 10 times higher

than the funding for hiv vaccines in any

given year

and we know that money drives innovation

it attracts

the best scientists and the best

industries into the

um you know into this area um

it helps us run more trials vaccine

development is expensive and it is

higher risk

we also need more industry involvement

we’ve certainly seen that in covet

many industries including industries

have never been involved in vaccine

development

are now getting involved but we do need

to incentivize them

and and one of the ways to incentivize

them is of course to give them advance

commitments

um so our governments need to do that

they need to say that we will buy the

vaccine

uh if it’s shown to be safe and

efficacious

there’s no doubt um that the covert

vaccine is going to have a major impact

it’s going to turn this epidemic around

it’ll save lives and it’ll save

livelihoods

what we need now is to also develop a

vaccine against hiv

so that we can do the same we need to

attract the best

people into this area we need to use

what we’ve learned

in developing covert vaccines we need to

apply that to hiv

so that we can have an aids-free world

thank

[Music]

you

[音乐]

我是一名实验室科学家

,在我职业生涯的最后 25 年里,

我一直在努力

研制艾滋病毒疫苗

,现在我们

在不到一年的时间里

就有了三种隐蔽疫苗 觊觎疫苗

从多年来对

艾滋病毒疫苗的投资中受益匪浅,今天我想告诉

大家的

是,我们如何利用这种势头来加速

艾滋病毒疫苗的开发,但首先让我们看看

它们肯定拥有的这两种病毒 一些相似之处,

你可以看到它们是微小的微观

病毒,你需要非常强大的

显微镜才能看到它们,

但也有一些显着的

差异,

所以导致 covet 19 的病毒 sar’s curvy ii

通过呼吸根传播,所以

这只是

呼吸而已 意味着每个人都

易感这种病毒会导致急性

感染

,这意味着它的寿命很短,并且

身体能够清除病毒

,正如我们所知,大多数人都会发生这种情况,

并且 因为我们的身体会对

病毒产生免疫反应,

特别是

几乎

每个人都会产生中和抗体,另一个重要特征是

这种病毒

非常稳定,所以

全世界

感染了这种病毒的 6000 万人都感染

了一种非常 相关病毒

有一些差异,但它现在

非常相似

,相比之下,艾滋病毒会导致慢性

感染

,这意味着它是终身

感染

,那是因为这种病毒整合

我们的遗传物质中进入我们的

DNA 另一个主要因素是中

和抗体 这里的反应

非常缓慢且无效,然后

艾滋病毒疫苗开发的另一个主要障碍

是病毒变异,它确实是一个

移动目标,

现在疫苗已成为我们

应对传染病最成功的方法之一

,大多数疫苗通过诱导

中和作用发挥作用 抗体这些

是我们免疫反应

和中和抗体的一部分 之所以起作用,是因为

它们

与病毒的某些部分特异性结合

嗯,通过中和,让我们

仔细看看这种

sars covi2 蛋白,这就是

导致病毒周围出现尖峰或冠状

病毒的原因

,科学家们已经能够

以所谓的非常

高的分辨率看到它,实际上

它又是 HIV 科学家们将

注意力

转向研究 sars curvy ii

蛋白,部分是因为

紧迫性,但也因为有大量

资金

可供人们研究隐蔽 19。但是

我们从结构中学到

的东西 刺突蛋白是

抗体靶向的部分

是一个非常集中的部分,

它是红色的部分,所以这是主要的

目标 我们正在寻找,

因为这是与细胞结合的蛋白质的一部分,

现在

已经针对 covet 19 制造了许多不同的疫苗,

而且它确实受益

于几十年来

针对 HIV 的疫苗开发,所以这 只是向您展示了一些

已采取的不同方法,

你们中的许多人会知道,我认为

我们家喻户晓的其中一些,呃,

这些疫苗制造商,所以

由 rna 或

尖峰病毒的 dna 组成的基因疫苗 蛋白质

用于刺激免疫反应

这些相同的基因也被放入

所谓的病毒载体中,

因此实际上

将这些基因

几乎像特洛伊木马一样携带到体内是一种无害的病毒,因此在这些

类型的疫苗中

,身体实际上是 制造刺突

蛋白

我们实际上是在以某种方式制造我们自己的疫苗

第三种疫苗称为

蛋白质疫苗

,这是我们在实验室制造蛋白质

的地方 然后

你知道用它来免疫人们,

这是一种更传统

的疫苗开发方法,

它需要更长的时间,

实际上更昂贵,

所以肯定有,而且

在媒体上广泛报道

了你知道 这项令人难以置信的

开发隐蔽疫苗的努力,现在我们知道我们

已经有三个

证明它们有效,它们

具有很高的功效

这两种 rna 疫苗被证明具有

超过 90 的

功效,并且载体

疫苗也非常好 功效,但正如

您从所谓的这条管道中看到的那样,

还有另外 10 个

仍在测试中 是

大量的疫苗,所以我们有一个

非常强大

的隐蔽疫苗开发管道,

虽然目前还没有获得许可,

但这也是非常迫在眉睫的

t 相比之下

,在进行 HIV 疫苗试验的 20 年中,我们在 20 年内只

进行了

六次功效试验,

所以

只是为了让您了解,嗯,您

知道区别

,以及我们如何解决这两个问题 病毒,

但我不想让它听起来好像

艾滋病毒疫苗的开发很容易,因为

这实际上不是

我们这个时代最大的挑战之一

,这真的是因为这种病毒

确实发生了变化,

所以我们

是我所在的实验室 nicd

一直在研究如何在感染者中开发这些

广泛中和的抗体

,我们在此过程

中发现,病毒

正在发生变化,

以产生获得

正确抗体所需的各种刺激

,因此 这个进化过程

现在正被纳入疫苗

设计

,所以范式是

我们需要不同的

不同疫苗来

引导抗体反应,这样它就可以

成为新的 追踪抗体反应,

这只是在此处以图形方式显示,

嗯,嗯,这

是艾滋病毒中刺突蛋白的等价物,

称为包膜蛋白

,因此每种不同的颜色都

表明它是一种略有不同的

包膜蛋白

,以便基本上 正如我所说

,沿着正确的途径诱导免疫反应

以产生中和抗体,

所以在疫苗开发方面,

你知道 HIV 会带来

一些重大挑战,所以

我参加了由这所大学开展的秘密疫苗

试验 novovax 试验

, 我这样做是因为我真的

相信疫苗,我相信疫苗的力量

,也因为我很脆弱,

就像你知道的其他人一样

被销售

曲线 2 感染。

所以我接种了两次疫苗

,你知道我有点想象 这种呃

蛋白质在我的体内循环,我的

b 细胞试图让你知道将其捕获,

这样它就可以

产生正确的抗体 是

为了让你知道保护我

嗯,你知道,在这段时间

里,有人保留了一份疫苗

日记,你记录了你的,嗯,你知道你的

体温,哪里有肿胀

或发红

,真的很轻微,嗯,

很相似

几天内真正解决的昆虫叮咬,

,当然我还不知道我是在

服用安慰剂还是疫苗的活性臂,

这只会在以后被

发现,这对于

嗯,

你知道确定疫苗的

工作原理是测量

接种过疫苗的人的免疫反应,

并确定所谓的

保护相关性,所以我们需要

知道

疫苗需要刺激的抗体水平

才能保护人们 免受感染,

这就是这些试验将

显示的非常关键的事情,事实上,

一旦我们有了保护的相关性,

实际上疫苗开发

过程将进一步加快

b 但我也知道,就像你知道的

一样

,我们在应对这种流行病的过程中一直在学习,我们仍然有

很多未知数,

所以我们不知道免疫力会

持续多久 我们不知道这些

疫苗是否会起作用 对于每个人来说,

嗯,虽然有很好的迹象

表明它们确实在老年人中起作用,他们

当然是主要的目标群体

嗯,我们不确定我们是否正在测量

正确的免疫反应,

嗯,因为可能还有其他

事情我们

你知道 仍然有待发现,我

认为一个非常关键的事情是,

你知道病毒会以

与艾滋病毒改变相同的方式发生变化,

并且代表一个问题,你知道

一旦许多人

对 sars 有免疫力,它就会

施加压力 关于病毒,所以这

是我们当然需要跟踪的事情之一,

所以现在我想看看

这两种流行病造成的全球破坏,

所以上面的

图表显示了

每周由 sars kovi ii 造成的死亡人数

从一开始 爆发,

你可以看到紫色是

在欧洲发生的第一波,

你可以看到现在正在发生的复苏

,然后你可以看到美国的

高水平和持续的死亡人数

,以及最严重的是 嗯,这张图表令人不安的

是,这些复苏水平

高于初始水平

,这确实说明了我们迫切

需要开始部署这些

活跃的这些有效疫苗,

因为如果我们不这样做,这些浪潮将

继续发生,

这种病毒将成为 地方性流行,

它将在 11 个月内继续在易感

人群中传播 到目前为止

,已有 140 万人

死于贪婪

19 我们当然不希望达到

我们看到的 3500 万人感染艾滋病毒的水平,

所以为什么有 3500 万人

死于艾滋病毒是因为艾滋病毒

已经伴随我们很长时间了

,正如你所知,我们没有疫苗,

但我们确实有很好的

抗逆转录病毒药物

您可以在下图中看到这些疗法的影响,

因此在艾滋病流行的高峰期,

每年约有 160 万人

死亡,

而这种下降是在抗逆转录病毒

疗法开始被广泛使用的时候,

但我们不会让我们 零,

因为抗逆转录病毒疗法治疗

受感染的人我们需要的

是我们需要防止人们

被感染,这就是为什么我们

需要疫苗

所以我们需要疫苗来使

曲线下降,

就在去年 2019 年有超过 70 万人

死于艾滋病毒,所以 关于这张图的另一个重要的事情

是颜色,所以你可以

看到它大部分是红色的,这是因为

艾滋

病毒主要影响非洲大陆,

但我们也知道历史

疫苗开发或非洲

在开发疫苗方面一直被忽视

影响非洲大陆的疾病,

我们可以从 covet 19 中学到什么,这

将有助于我们

更快地开发艾滋病毒疫苗,那么我们可以从 covet 19 中学到

什么? 我们需要做的是测试

开发和测试多个

候选人

我们需要一个强大的管道,就像

我们对隐蔽所做的一样我们

需要测试许多不同的概念

,同时测试它们我们

当然需要测试

最初为 HIV 开发的 mrna 疫苗,

但你知道现在正在

接受隐蔽

测试 我们需要寻求

批准

它的风险很高,但

它是它的快速跟踪过程,

我们当然需要更多的钱,

所以隐蔽 19 花在隐蔽 19 上的金额

是任何给定的艾滋病毒疫苗资金的 8 到 10 倍

,我们知道,金钱推动创新,

它吸引

了最优秀的科学家和最优秀的

行业

进入这个领域,嗯,

它帮助我们进行更多的试验,疫苗

开发是昂贵的,而且它是

更高的风险

我们还需要更多的行业参与

我们当然已经看到,

许多行业,包括

从未参与疫苗

开发

的行业现在都参与其中,但我们确实

需要激励他们

,激励

他们的方法之一当然是 给他们预先的

承诺,

嗯,所以我们的政府需要这样做,

他们需要说我们将购买

疫苗,

嗯,如果它被证明是安全

有效的,毫无疑问,秘密

疫苗将产生重大影响。

扭转这种流行病

它将挽救生命 将挽救

生计

我们现在需要的是开发一种

艾滋病疫苗,

这样我们就可以做同样的事情 我们需要

吸引最优秀的

人进入这个领域 我们需要使用

我们的东西

在开发隐蔽疫苗方面学到了我们需要

将其应用于艾滋病毒,

这样我们才能拥有一个没有艾滋病的世界

谢谢

[音乐]