Free for all! China's first new crown vaccine on the market, here are all the seven questions you want to know

一天之内就批准了。

It was approved in one day.

12月31日，即2020年的最后一天，根据国务院联合防控机制发布的信息，国药生物新皇冠疫苗获国家食品药品监督管理局批准有条件上市。

On December 31, the last day of 2020, according to the information released by the joint prevention and control mechanism of the State Council, Sinopharm sinobio's new crown vaccine was approved by the State Food and Drug Administration for conditional marketing.

这是中国第一种新疫苗。

This is the first new vaccine in China.

从2020年下半年开始，国内外各机构研制的新型疫苗陆续传出好消息。他们目前的进展如何，有什么不同？

From the second half of 2020, the new vaccine developed by various institutions at home and abroad has been spreading good news one after another. What is their current progress and what are their differences?

根据各方的信息，我们整理了两张表供大家参考。

Based on the information of all parties, we have sorted out two tables for you to see.

新型冠状苗在我国的市场营销与研发进展

Progress of marketing or research and development of new crown vaccine in China

首先，第一种疫苗已经上市。谁应该先接种疫苗？

First of all, the first vaccine is on the market. Who should be vaccinated first?

早在12月15日，我国就已对部分重点人群实施了新型皇冠疫苗接种，累计接种量已超过300万剂。这一次，将有序开展对老年高危人群的疫苗接种工作。

As early as December 15, China has carried out the new crown vaccination for some key groups, and the cumulative vaccination has exceeded 3 million doses. This time, the vaccination will be carried out for the elderly people with high-risk diseases in an orderly manner.

此前，推荐的焦点群体主要有9类：

Previously, the recommended focus groups were mainly 9 categories:

1海关检查员参与进口冷链食品

1. Customs inspectors involved in import cold chain food

2港口装卸、装卸、运输等相关人员

2. Port loading and unloading, handling, transportation and other related personnel

三。国际运输从业人员

3. International and domestic transportation practitioners

4因公出国留学

4. Study abroad for business and private

5国境口岸工作人员面临更高的海外风险

5. Frontier port staff facing higher overseas risks

6医疗卫生人员

6. Medical and health personnel

7公安、武警、消防社区工作人员

7. Public security, armed police, fire community staff

8水、电、暖、气相关人员

8. Water, electricity, heating and gas related personnel

9交通、物流、养老、环卫、殡葬、通讯等相关工作人员

9. Transportation, logistics, pension, sanitation, funeral, communication related staff

尚未发现影响疫苗效力的突变。

No mutation has been found to affect the efficacy of the vaccine.

科学家们都关心病毒变异的问题。作为一种RNA病毒，新冠状病毒的突变有望出现。关键是突变是否在S蛋白上。当突变累积到一定程度时，可能会降低现有疫苗的保护效果。

Scientists are all concerned about the problem of virus mutation. As an RNA virus, the mutation of new coronavirus is expected. The key is whether the mutation is on S protein. When the mutation accumulates to a certain extent, it may reduce the protective effect of the current vaccine.

近年来，英国变异新冠状病毒S蛋白上出现了一个备受关注的突变位点，可能使病毒更容易侵入细胞。但一般认为该突变仍在正常范围内，且突变速度远慢于流感病毒，对疫苗效果影响不大。

Recently, a highly concerned mutation site appeared on the S protein of British mutant new coronavirus, which may make the virus easier to invade cells. However, it is generally believed that this mutation is still in the normal range, and the mutation speed is much slower than that of influenza virus, which has little impact on the vaccine effect.

如果有一天疫苗的有效性真的受到影响，开发多价疫苗就能解决这个问题。

If one day the effectiveness of the vaccine is really affected, the development of a multivalent vaccine can solve this problem.

所谓多价疫苗是将同一病原体或不同病原体（如DPT）的不同致病类型纳入疫苗。目前使用的疫苗有多种，如脑膜炎球菌4价多糖疫苗、肺炎13价结合疫苗、宫颈癌9价疫苗等。

The so-called multivalent vaccine is to include different pathogenic types of the same pathogen or different pathogens (such as DPT) into the vaccine. There are many vaccines in service, such as meningococcal 4-valent polysaccharide vaccine, pneumonia 13 valent conjugate vaccine, cervical cancer 9-valent vaccine, etc.

我们的策略是先生产单价疫苗。如果我们需要制造多价疫苗，我们可以将其添加到疫苗中，这不是很困难。因此，我们不必过于担心病毒突变。

Our strategy is to make the univalent vaccine first. If we need to make the multivalent vaccine, we can add it to the vaccine, which is not very difficult. Therefore, we do not have to worry too much about virus mutation.

疫苗成功的关键是防止病毒感染宿主细胞。

The key to the success of the vaccine is to prevent the virus from infecting the host cells.

原则上，新冠状病毒的入侵机制已经很清楚

In principle, the invasion mechanism of new coronavirus has been clear

正是病毒表面的S蛋白与人体细胞表面的血管紧张素转换酶2（ACE2）受体结合，吸附在细胞上并侵入细胞。

It is the S protein on the surface of the virus that binds to the angiotensin converting enzyme 2 (ACE2) receptor on the surface of human cells to adsorb on the cells and invade them.

人体对s蛋白的免疫反应产生的抗体能与s蛋白结合，使病毒失去吸收人体细胞的能力，从而可以防止感染。

The antibody produced by the human body's immune response to S protein can combine with S protein, making the virus lose the ability to absorb human cells, which can prevent infection.

1灭活疫苗

1. Inactivated vaccine

安全性高，技术成熟，只刺激体液免疫，生产受场地限制

High safety, mature technology, only stimulate humoral immunity, production is limited by the site

灭活疫苗的主要活性成分是灭活病毒颗粒，它包含了病毒的所有结构成分，接近或等于天然病毒颗粒。

The main active component of inactivated vaccine is inactivated virus particles, which contains all the structural components of the virus and is close to or equal to the natural virus particles.

目前，儿童常用的灭活疫苗有小儿麻痹症灭活疫苗、甲肝灭活疫苗、手足口疫苗、全民常用的狂犬病疫苗（孕妇可接种）。

At present, inactivated vaccines commonly used by children include polio inactivated vaccine, hepatitis A inactivated vaccine, hand foot mouth vaccine, and rabies vaccine commonly used by the whole population (pregnant women can be vaccinated).

然而，灭活疫苗也有一些缺点

However, inactivated vaccine has some disadvantages

一是不能模拟病毒感染过程，对免疫系统的刺激性较弱；

First, it can't simulate the process of virus infection, and its stimulation to the immune system is relatively weak;

第二，生产高水平的活疫苗和灭活病原体是必须的。

Second, it is necessary to cultivate live pathogens first, and then inactivate them to make vaccines, which requires a high level of biosafety in the production workshop and limits the production.

对于新的冠状病毒，它包含四种结构蛋白（s、e、m、N蛋白）和更多其他蛋白[19]。

For the new coronavirus, it contains four structural proteins (s, e, m, N proteins) and more other proteins [19].

如果证实s蛋白是形成免疫的关键成分，灭活疫苗中还含有其他组分蛋白，则相当于在相同剂量的疫苗下，灭活疫苗的s蛋白比例低于其他类型疫苗，且有效成分减少，从而降低了免疫效果可能不利于产生足够的免疫反应。

If it is confirmed that s protein is the key component in the formation of immunity, and inactivated vaccine also contains other component proteins, it is equivalent to that under the same dose of vaccine, the S protein proportion of inactivated vaccine is lower than that of other types of vaccines, and the effective components are reduced, which may not be conducive to producing enough immune response.

这样，在病毒培养和疫苗制备过程中，宿主蛋白或其他杂质极易被截留，不仅影响免疫效果，而且增加了发生不良反应的可能性。

In this way, in the process of virus culture and vaccine preparation, host protein or other impurities may be easily retained, which may not only affect the immune effect, but also increase the possibility of adverse reactions.

2重组蛋白疫苗

2. Recombinant protein vaccine

高效安全，生产能力强

High efficiency and safety, high production capacity

重组蛋白疫苗技术相对成熟，许多产品已进入市场。

The technology of recombinant protein vaccine is relatively mature, and many products have entered the market.

这种疫苗的实质是通过基因工程将有效的抗原成分转化，在其他细胞中完成蛋白表达，然后分离目标蛋白，添加保护剂等，最后包装成市售疫苗。

The essence of this kind of vaccine is to transform the effective antigen components through genetic engineering, complete protein expression in other cells, then isolate the target protein, add protective agents, etc., and finally package it into a commercially available vaccine.

乙型肝炎疫苗是重组蛋白疫苗的鼻祖，已经使用了30年。此外，还有戊型肝炎疫苗、宫颈癌疫苗和带状疱疹疫苗。

Hepatitis B vaccine is the originator of recombinant protein vaccine, which has been used for 30 years. In addition, there are hepatitis E vaccine, cervical cancer vaccine and herpes zoster vaccine.

重组蛋白疫苗的靶点非常准确，是病原菌的关键蛋白成分，其效果和安全性可能优于灭活疫苗。其生产过程不会产生活病原体，对生物安全性要求较低。培养细胞生产病原蛋白的效率很高，因此生产能力也高于灭活疫苗。

The target of recombinant protein vaccine is very accurate, which is the key protein component of pathogen, so its effect and safety are likely to be better than inactivated vaccine. Its production process will not produce living pathogens, and the requirement for biosafety is low. The efficiency of culturing cells to produce pathogen protein is very high, so the production capacity is also higher than that of inactivated vaccine.

当然，重组疫苗也有缺点——由于表达宿主的限制，克隆的蛋白往往与天然蛋白不同，这可能影响免疫原性。后期需要净化、分离、包装，还面临杂质问题。

Of course, the recombinant vaccine also has disadvantages - due to the restriction of the expression host, the cloned protein is often different from the natural protein, which may affect the immunogenicity. In the later stage, it needs to be purified, separated and packaged, and also faces the problem of impurities.

三。病毒载体疫苗和核酸疫苗

3. Viral vector vaccine and nucleic acid vaccine

生产能力最高，但不良反应较多，安全性有待观察

The production capacity is the highest, but there are more adverse reactions, and the safety remains to be seen

这两种技术是将编码病毒S蛋白的基因导入人体细胞，让人体细胞自行产生S蛋白。

These two technologies are to transfer the gene encoding virus S protein into human cells and let human cells produce s protein by themselves.

前者以无害病毒（如腺病毒）为载体，将s蛋白基因导入人体；后者直接将s蛋白基因导入人体细胞。

The former uses harmless virus (such as adenovirus) as vector to transfer s protein gene into human body; the latter directly transfers s protein gene into human cells.

当"疫苗图纸"送到人体时，人体可以根据"图纸"生产疫苗。真是太神奇了。

When the "vaccine drawing" is sent to the human body, the human body can produce the vaccine according to the "drawing". It's really amazing.

DNA疫苗可能整合到人类基因中，其安全性有待观察，因此进展缓慢。

DNA vaccine may be integrated into human genes, and its safety remains to be seen, so the progress is slow.

很容易得到大规模生产疫苗的蓝图，特别是其他两种疫苗。

It's easy to get the blueprint for mass production of vaccines, especially for the other two types of vaccines.

在应用于新的冠状病毒疫苗之前，mRNA疫苗只在不到2000人身上进行了试验[21]，更不用说在市场上了，所以它的安全性和有效性还有待观察。

Before being applied to the new coronal vaccine, the mRNA vaccine has only been tested on less than 2000 people [21], let alone on the market, so its safety and effectiveness remain to be observed.

从新型冠状病毒mRNA疫苗来看，其有效性已得到认可，但在安全性方面，其常见不良反应率明显高于灭活疫苗。

From the point of view of the new coronal mRNA vaccine, its effectiveness has been recognized, but in terms of safety, its common adverse reaction rate is significantly higher than that of the inactivated vaccine.

一般认为，mRNA疫苗可以刺激抗体免疫和细胞免疫。

It is generally believed that mRNA vaccine can stimulate antibody immunity and cellular immunity.

因此，mRNA疫苗需要在细胞免疫方面得到很好的控制。

Therefore, the mRNA vaccine needs to be well controlled in cellular immunity.

细胞免疫就像警察，其主要功能是"发现犯罪现场"，清除被病毒感染的细胞，维持较长时间的免疫力；

Cellular immunity is like the police, whose main function is to "discover the crime scene", clear the cells infected by the virus, and maintain immunity for a longer time;

它就像一辆免疫车，失去了对病毒的控制能力。

Antibody immunization is like a police car, which can control the virus and make it lose the ability to infect cells.

如果产生足够的抗体，病毒就不能感染新的细胞，被感染的细胞就会死亡，所以简单的抗体免疫也可以保护身体；

If enough antibodies are produced, the virus can not infect new cells, and the infected cells will die, so simple antibody immunity can also protect the body;

随着细胞免疫力的提高，体内受感染的细胞将被更有效地清除，病毒将被更好地清除，健康将得到恢复。

With the increase of cellular immunity, the infected cells in the body will be removed more effectively, the virus will be removed better and the health will be restored.

人体临床试验分为三个阶段。第三阶段是验证疫苗对社会人群的保护作用。因此，三期临床试验必须在该病相对流行的地区进行。

Human clinical trials are divided into three phases. Phase III is to verify the protective effect of the vaccine in the social population. Therefore, phase III clinical trials must be carried out in areas where the disease is relatively prevalent.

志愿者分为疫苗组和安慰剂组。如果疫苗组的患者数量远低于安慰剂组，疫苗就具有保护作用。

The volunteers were divided into the vaccine group and the placebo group. If the number of patients in the vaccine group was much lower than that in the placebo group, the vaccine had protective effect.

这就要求这两组志愿者必须有较高的感染机会，而我国的疫情控制太好，感染的机会太渺茫，所以我们要出国做三期临床试验。

This requires that the two groups of volunteers must have a higher chance of infection, and China's epidemic control is too good, the chance of infection is too slim, so we have to go abroad to do phase III clinical trials.

目前，现役使用疫苗的经验是，疫苗的安全性和有效性不分种族。因此，新疫苗对外国人的检测结果可以外推到中国人身上。

At present, the experience of using vaccines in active service is that the safety and effectiveness of vaccines do not distinguish race. Therefore, the test results of the new vaccine on foreigners can be extrapolated to Chinese people.

然而，一般来说，需要一个相对简单的"桥接试验"来证实这一点，但这比进行三期临床试验要容易得多。

However, generally speaking, a relatively simple "bridging test" is needed to confirm this, but it is much easier than conducting phase III clinical trials.

例如复星医药引进了德国生物技术公司的mRNA疫苗，该公司已获授权在英国和美国开展紧急疫苗接种。这种疫苗目前正在江苏省疫苗临床试验基地进行960人的桥接试验[22]。

For example, Fosun medicine introduced the mRNA vaccine of German biotech, which has been authorized to carry out emergency vaccination in the United Kingdom and the United States. This kind of vaccine is currently being carried out in 960 people's bridging test in the vaccine clinical trial base in Jiangsu Province [22].

需要强调的是，急诊患者和临床试验人群不是同一人群，不能纳入临床试验数据。不过，对于紧急使用还会有一些后续观察，也可以了解疫苗的安全性和有效性，可以作为疫苗研制过程的补充证据。

It should be emphasized that the emergency users and the clinical trial population are not the same population and cannot be included in the clinical trial data. However, there will be some follow-up observation for emergency use, which can also understand the safety and effectiveness of the vaccine, and can be used as supplementary evidence for the vaccine development process.

目前，维持疫苗保护效果的时间尚不确定。

At present, the time of maintaining the protective effect of vaccine is uncertain.

根据世界各地受感染者的再感染情况和早期疫苗临床试验志愿者的抗体跟踪调查，一般认为疫苗的保护效果至少半年[24]。

According to the reinfection situation of infected people around the world and the antibody tracking survey of volunteers in early vaccine clinical trials, it is generally believed that the protective effect of the vaccine is at least half a year [24].

如果将来减少保护，可以通过添加代理次数来解决问题。就个人而言，新的皇冠疫苗不太可能像流感疫苗那样每年都需要接种。

If the protection is reduced in the future, the problem can be solved by adding agent times. Personally, the new crown vaccine is unlikely to need to be vaccinated every year like the flu vaccine.

要实现重点人群的大规模免疫，接种率至少要达到70%。必须对疫苗的安全性进行科学的阐述，否则就会成为疫苗接种的障碍。

In order to achieve mass immunization in the key population, the vaccination rate should be at least 70%. It is necessary to make a scientific exposition on the safety of the vaccine, otherwise it will become an obstacle to vaccination.

疫苗与科学博士dorina进行的一项在线调查显示：

An online survey conducted by Dr. dorina, vaccine and science, shows that:

在参与调查的834人中，如果不愿意接种，最可能的原因是担心安全，占67%，其次是不愿意承担费用（16%），担心效果（9%）。

Among the 834 people who participated in the survey, if they were not willing to vaccinate, the most likely reason was that they were worried about safety, accounting for 67%, followed by unwilling to bear the cost (16%) and worrying about the effect (9%).

从目前复星医药引进德国生物技术公司mRNA疫苗的经验来看，该疫苗已通过国外三期临床试验，证实了其有效性和安全性，然后在中国进行了一期和二期临床试验，以确认疫苗对国内人群的安全性和免疫效果（不是保护效果）。

From the current experience of Fosun medicine's introduction of German biotech's mRNA vaccine, this vaccine has passed the phase III clinical trial abroad and confirmed its effect and safety, and then the phase I and phase II clinical trials have been carried out in China to confirm the safety and immune effect (not protective effect) of the vaccine on the domestic population.

更进一步说，可能需要也可能不需要第三阶段临床试验。由于没有成功上市的案例，要看国家审批机关如何决策。

To go further, phase III clinical trials may or may not be needed. As there is no successful listing case, it depends on how the state examination and approval authorities make decisions.

在2020年的最后一天，我们终于迎来了一个好消息：中国第一种新型皇冠疫苗即将上市。随着越来越多的人接种疫苗，我们面对病毒的基础更加牢固。双节快到了，我们出行的时候还需要做好保障，相信我们最终会赢的！

On the last day of 2020, we finally welcome the good news that China's first new crown vaccine is on the market. As more and more people are vaccinated, we have a stronger base in the face of the virus. The double festival is approaching, we still need to do a good job of protection when we travel, I believe we will win in the end!

特约作者：陶丽娜，复旦大学疫苗学硕士、公共卫生管理硕士

Special authors: Tao Lina, a master of vaccine science, master of public health management, Fudan University

审稿人：中国疾控中心病毒性疾病预防控制研究所助理研究员、免疫学博士卢学新

Reviewer: Lu Xuexin, assistant researcher and doctor of immunology, Institute of viral disease prevention and control, CDC

参考

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[26]https://app.biorender.com/biorender-templates/t-5f178d344f5fad00a7792332

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Link：https://new.qq.com/omn/20210101/20210101A028JN00.html

update time：2021-01-01 14:30:54