Video在线视频

大家下午好
-Good afternoon.

我是Brigitte Gicquel
I am Brigitte Gicquel.

我在巴斯德研究院和上海巴斯德研究所工作
I work at the Institut Pasteur in Paris and Shanghai

带领两个负责诊断和药物研发的团队
and I head two teams working on diagnosis and drug discovery.

今天
Today,

我会谈论疫苗和不同的机理
I will speak about vaccination and different subjects.

预防接种是预防和消除传染病最好的方法
Vaccination is the best way to prevent and eliminate an infectious disease.

爱德华·詹纳（Edward Jenner）
The first vaccine was elaborated by Edward Jenner

在观察到牛痘（一种牛的疾病也称为牛痘苗）
after observing that cowpox,

保护人类免受天花（一种非常严重的疾病）
a cow disease also called vaccine,

感染后 发明了疫苗
was protecting humans against smallpox, a very important disease.

事实上
Indeed,

这两种疾病是由属于痘病毒科的病毒引起的
these two diseases are caused by viruses belonging to the pox family and the animal virus,

而动物类痘苗病毒
the Vaccinia virus,

可以保护人类免受天花侵害
 protects humans against smallpox.

这是一个非常重要的发现
This is a very important discovery

因为它的应用消灭了天花
because its utilization has resulted in the disappearance of smallpox from the world.

还有诱导免疫应答的其它方式
Other ways of inducing immune responses are possible.

例如
For instance,

我们可以用细菌或灭活的病毒
we could construct vaccines using bacteria,

或其片段构建疫苗
or viruses that are inactivated,

然后接种到人体中
or fragments of them,

这样这些片段就会遇到幼稚T细胞
and inoculate them to humans so that these fragments will encounter naive T cells

从而形成记忆T细胞
that will form memory T cells.

这些记忆T细胞遇到感染性病原体后
These memory T cells will proliferate and will be activated

被激活并增殖
after encountering an infectious agent,the disease,

迅速地引发免疫反应
and provoke an immune response more rapidly.

但在结核病中 这是不可能的
However, in the case of tuberculosis this was not possible.

自从罗伯特·科赫（Robert Koch）
After the discovery of the bacilli

发现杆菌后
by Robert Koch,

无法培养 灭活 
it has been impossible to use these bacilli to culture them, inactivate them,

采集碎片来制造疫苗
take fragments and have a vaccine.

一些研究人员试图用牛型分枝杆菌
Some researchers have tried to use the bovine bacilli,

而不是人类的细菌
not the human bacilli,

来诱导保护人体免受结核病侵害
the bovine bacilli, to induce protection against tuberculosis in humans.

然而
However,

牛型分枝杆菌也具有传染性
the bovine agent is also infectious

可以引发结核病
and provokes tuberculosis.

这种行为被禁止了
This initiative has been stopped.

通过对牛型结核杆菌的研究
The bovine tuberculosis agent was studied

Calmette（卡医生）
and it was found by Calmette

和Guerin（介医生）发现
and Guerin

经过多次传代后
that after a series of passages of bovine tuberculosis agents,

结核杆菌会失去活性
these agents turned out to be inactivated.

以马铃薯切片和牛胆汁
There were cultures of M.bovis on potato slices plus ox bile

作为牛分枝杆菌的培养基
used as a medium

经过100多次传代后
and after a succession of over 100 passages,

细菌完全失去毒性
they had a completely attenuated culture.

在动物模型和人类中不仅完全减毒
Not only completely attenuated but protective against tuberculosis

而且能预防结核病
in animal models and humans.

这是婴儿最早接种的疫苗之一
Here is one of the first vaccinations of babies.

婴儿是重点对象
Babies were the problem

因为小儿结核病是非常严重的问题
because pediatric tuberculosis was a very big problem.

从结核感染的母亲所生的婴儿开始接种疫苗
Vaccination has started with babies born from tuberculosis-infected mothers.

这些婴儿在接种疫苗后存活下来
These babies survived vaccination

并且可以免疫一种严重的结核病
and have been protected against the severe form of tuberculosis,

血行播散型结核性脑膜炎
the disseminated tuberculous meningitis.

这是非常重要的一点
It is a very important point.

但几年后出现了抗生素在一些国家
However, a few years later antibiotics appeared and in several countries,

人们宁愿治疗病人
people preferred treating patients

而不是接种疫苗
instead of vaccinating them,

用预防性治疗方式治疗病人和接触者
treating patients and contacts with preventive therapies.

了解卡介苗的效果非常重要
It was important to know the efficacy of BCG.

许多机构
Several trials

特别是世界卫生组织进行了几次试验
were undertaken by different institutions, in particular the WHO.

这是对这项研究的荟萃分析
Here is a meta-analysis of this research.

显而易见 卡介苗的效果波动很大
It is obvious that the efficacy of BCG is very variable,

从接近0到非常高的效果
going from around 0 to a very high efficacy.

我们在这些试验中看到的
What we see in these trials is that the vaccine

是疫苗对成年人的肺结核不是非常有效
is not very efficient for the adult population against the pulmonary form of tuberculosis.

但是 保护儿童免受像脑膜炎
However, it is very efficient to protect children against the severe

这样的严重结核病是非常有效的
form of tuberculosis like meningitis.

这就是世界卫生组织建议
This is why the WHO recommends vaccinating children

在结核病高发国家给儿童接种卡介苗的原因
with BCG in countries with a high incidence of tuberculosis.

同时建议给低发国家中患结核病的婴儿
It is also recommended to vaccinate infants in low-incidence countries for tuberculosis

和接触结核病的儿童接种疫苗
and children living in contact with tuberculosis.

卡介苗是一种活疫苗
BCG is a live vaccine

因此它在免疫力受损人群中是禁止使用的
and therefore it is contraindicated in people with impaired immunity.

此外 不建议为HIV阳性的儿童接种疫苗
Also, it is not recommended to vaccinate HIV-positive children.

但是 很多情况下
However, it is difficult to know

很难了解儿童血清中HIV阳性情况
the situation of HIV seropositivity in children in many settings

需要慎重决定
and important decisions will have to be made.

无论如何 我们需要卡介苗以外的新疫苗
Anyhow, we need a new vaccine other than BCG to vaccinate

来接种和保护成年人群
and protect adult populations.

这就是欧洲成立结核病疫苗倡议组织（TBVI）
This is why TBVI, the Tuberculosis Vaccine Initiative, in Europe has set up a foundation

来支持开发新疫苗抗击结核病运动的原因
to support actions against tuberculosis with the construction of new vaccines.

很多欧洲的实验室一直合作研发
A lot of European laboratories have been working together

并发现了一系列候选疫苗
and have proposed a series of vaccine candidates.

但如何进行
But how to proceed?

我们需要知道有效防止结核病的免疫反应
We need to know the immune responses that are efficient for protection against tuberculosis.

一系列的研究表明
A series of works have shown

产生γ干扰素的Th1应答是保护性的
that it is the Th1 response producing interferon-gamma which is protective.

CD8应答也是保护性的
The CD8 response is also protective.

然而 这是不够的
However, this is not sufficient

必须发现其它反应
and other responses have to be discovered that will be efficient

才能有效开发疫苗的全面效能
to have a full efficacy for a vaccine.

所以不同的疫苗被分开
So, different vaccines have been isolated.

来自结核分枝杆菌的抗原具有辅助
There are antigens from M.tuberculosis with adjuvant

或重组病毒载体的功能
or recombinant viral vectors

如表达结核抗原的牛痘
like Vaccinia expressing TB antigens,

减毒的结核分枝杆菌突变体
also attenuated Mycobacterium tuberculosis mutants,

以及表达修饰抗原
and recombinant BCG expressing modified antigens

或诱导免疫应答的重组卡介苗
or inducing immune responses.

已经在2a期试验中测试的第一种疫苗
The first vaccine that has been tested in phase-2a trial

是改良的Ankara病毒这是一种痘苗病毒
is the Modified Virus Ankara,

在2b期试验中用来自结核分枝杆菌的
the Vaccinia virus, recombinant for the 85 antigen

85抗原重组得到
from Mycobacterium tuberculosis in a phase-2b trial.

不幸的是 这个试验失败了
Unfortunately, this trial has failed

尽管这种疫苗在动物模型豚鼠中
although this vaccine was protective in an animal model,

是具有保护性的
the guinea pig.

这里
It is here.

你可以看到卡介苗接种的结果
You see the results of vaccination with BCG

其中增加了痘苗病毒重组体
with a boost of the Vaccinia virus recombinant.

能看到保护作用比卡介苗
You see that the protection

或没有接种疫苗要好
is better than BCG or no vaccination.

然而在人体试验期间
However, during the human trials,

这两个接种疫苗没有太大区别
you see here the two vaccination arms, and there is not much difference.

这意味着疫苗的接种不起作用
It means that the vaccination does not work at that point.

我们还有很多工作要做
A lot more work remains to be done.

这里你可以看到在测试中的不同候选疫苗
Here you can see different vaccine candidates under testing.

其中之一是MTBVAC
One of them is MTBVAC,

这是由萨拉戈萨大学
a vaccine constructed by the University of Zaragoza

与我们的实验室合作开发的疫苗
in collaboration with our laboratory.

它是减毒的结核分枝杆菌
It is attenuated Mycobacterium tuberculosis bacilli.

在第一阶段试验中显示无毒性
It showed innocuity in phase-1 trials

并且还有诱导免疫反应和记忆反应的可能性
and also the possibility to induce immune responses and memory responses.

我们将要进行第二阶段试验
We are going to undertake the phase-2 trials.

将和许多其他候选疫苗一起进行
This will be done for many other candidates.

在这一点上
At this point,

我们认为有可能存在比卡介苗更好的疫苗
we believe that it will be possible to have a better vaccine than BCG.

如果我们想要像消灭天花一样消灭结核病
It is extremely important if we want to eliminate tuberculosis

这点是非常重要的
as it has been done for smallpox.

谢谢大家
Thank you.