Article from: Tencent. , author: Tencent News “periscope” Luo Fei

In the past two weeks, dozens of countries have adopted the strictest policies in the hope that they can work hard to intercept a new human enemy: the new coronavirus.

But interception is only the first step to defeat the virus and save the world. In the end, there is only one way to develop an effective vaccine. As Bill Gates said on March 19, “We will need billions of doses of vaccines to protect the world.”

With the global spread of the epidemic, a vaccine research and development competition has begun.

On March 17, the Chen Wei team of the Academy of Military Medical Sciences of the Chinese Academy of Military Sciences announced that the recombinant crown vaccine developed by their team was approved to start human clinical trials, and clinical volunteers are now being recruited. The design of the clinical trial showed that the Phase 1 clinical trial was divided into three groups of 36 people each.

The day before, American vaccine company Moderna also started clinical trials in Seattle and vaccinated the first volunteer. Moderna is a biomedical company based on mRNA as a technology platform.

As of March 19, the WHO said that 41 companies and institutions have been engaged in the development of new crown virus vaccines. But according to Tencent News “Perspective” statistics, there have been more than 50 companies and institutions actually participating.

Dozens of runners are racing together. Who successfully “runs out” the first vaccine on the market will be written into history as the protagonist of saving the world.

A person who participated in the National Key Vaccine Project Team estimated Tencent News’ “Perspective”. According to the current progress, The New Crown Virus vaccine representing China Power could be launched as soon as the end of the year, or it will become a competition First place.

Technology leader mRNA vaccine

On March 18, the new crown virus vaccine was first tested in humans. Moderna’s Seattle Institute gave a volunteer the first vaccine-only 22 days after the company delivered the vaccine to government researchers.

Such rapid vaccine development has set a record. The mRNA technology route selected by Moderna has attracted the most attention in the development of the new crown vaccine because of its multiple advantages such as strong immune activity and short development cycle.

The German company BioNTech is also taking this technical route. It is expected to enter clinical trials in late April. The commercialization in China will be handled by Fosun Pharma.

A similar case is happening in China. Zhuhai Livanda Biotechnology Co., Ltd., which also develops a new crown virus vaccine using the mRNA technology platform, (hereinafter referred to as “Livanda”) , its chairman Peng Yucai revealed that their team started the new crown virus vaccine project on January 22, completed the vaccine preparation in the laboratory on January 31, and injected it into mice and monkeys on February 1.

According to the introduction, Livanda is a biotechnology company located in Zhuhai Hengqin New District. Its team started to develop vaccines for mRNA technology as early as 2017. Peng Yucai, the leader of Rifanda’s new crown virus vaccine project, has been a senior at Bojian (Biogen) Scientist and team leader with decades of experience.

What excites Peng Yucai is that on February 12, they discovered that there are strong antibodies in animals. Unlike Moderna’s direct human trials for preemptive speed, all domestic mRNA vaccines, including Peng Yucai, need to strictly abide by existing vaccine management methods, and then perform human trials after completing animal model tests.

However, Moderna, which partnered with the National Institutes of Health, chose to reduce this link. Perhaps this is based on the fact that Moderna has previously developed vaccines similar to coronaviruses such as MERS.

The company’s chief medical officer, Tal Zaks, told US local medical media “STAT” that it does not consider proof in animal models to be the key to its use in clinical trials.

Despite thisThis approach can indeed speed up vaccine development, but it does not mean risk-free. Many scientists have criticized Moderna for doing so in violation of vaccine ethics.

A professional who has been engaged in vaccine research and development for many years told “Perception” that although the experimental data on mice are good, they should continue to do animal model tests, such as experiments on cynomolgus monkeys and rhesus monkeys. These large animals are closer to the human body. The purpose of animal model data is also to test the safety and effectiveness of vaccines in order to screen out vaccines that are more suitable for human experiments.

However, I haven’t seen Moderna’s data on animal models, and I hope I can bet once.

Before that, the mRNA vaccine of Moderna has also failed, such as Zika developed in 2017. 1325, because it did not achieve the expected results in the first phase of the clinical phase, it was changed to the development of the mRNA-1893 vaccine in early 2019.

Peng Yucai told Tencent News “Perspective” that in the field of mRNA, Moderna has good experience, and it has launched multiple phase II and phase III clinical trials of multiple vaccines. More importantly, mRNA vaccines are indeed much safer than traditional inactivated vaccines.

In terms of ethics, as long as the subjects are fully informed before the vaccine is injected, there is not much problem. The only possible trouble is that the final clinical trial results of Moderna were not as good as expected, and the vaccine development process was returned. After all, one of the purposes of animal model experiments is to screen out the most safe and effective vaccine for humans before going to the clinic.

The biggest advantage of mRNA technology is its ability to quickly prepare vaccines for research and development in the laboratory. Peng Yucai recalled that from the start of the project to the vaccination of mice, Livanda actually took less than 10 days-much faster than Moderna.

All the experimental results, they have maintained close communication with relevant departments. During the approval process of the new crown virus, Peng Yucai thought that this was an unprecedented speed. “Give the materials on the first day and get feedback the next day.”

However, according to the current vaccine development process in China, Peng Yucai and his team started animal model tests in early March, that is, primates such as monkeys were injected with vaccines, and then the new crown virus was injected to observe the effect. Expected 3At the end of the month, the primate feeding was finished.

Peng Yucai is distressed that this part of the test can only be performed in a laboratory with P3 and above, but many tests need to be scheduled during the epidemic. For private enterprises, it was not easy for Peng Yu to find a suitable laboratory for Livanda.

This is one of the reasons why Peng Yucai and his team originally completed vaccine preparation earlier than American Moderna, but still have not completed animal experiments. Fortunately, on March 18, Peng Yucai revealed that they finally found the cooperation with Kunming Institute of Biology, whose laboratory is qualified to complete subsequent animal experiments.

According to Peng Yucai’s prediction, Rifanda can complete the experimental part of the animal model as soon as April 15. At the same time, they are also starting to design clinical trials. Once the report and clinical design are completed, Peng Yu will submit clinical application materials to government departments.

Like Peng Yucai, most people hope that this time the new technology mRNA will be out on the track of the new crown vaccine. But so far, no mRNA vaccine has been put on the market.

At the same time, including the Chinese Academy of Military Sciences, there are at least 4 companies and institutions in China that are doing vaccine development in the direction of mRNA. Of the 41 new crown vaccine projects currently published by the WHO, 7 are in the RNA direction.

With so many new vaccine projects in the direction of mRNA, there will inevitably be some escorts-this is one of the risks that vaccine researchers need to consider.

China Power will be listed at the end of the year at the earliest

Although the US Moderna is ahead of other companies in the mRNA technology route, the scientific research team led by Academician Chen Wei, Academician of the Military Medical Research Institute of the Chinese Academy of Forces Military Science, leads the world on another track.

On March 17, they announced that they had successfully developed a recombinant new crown vaccine, and were approved to start clinical trials. Volunteers were vaccinated on March 19. At the same time, Academician Chen Wei’s team also made preliminary preparations for safety, effectiveness, controllable quality and mass production. According to the clinical design, the last observation time point of the phase 1 clinical trial of the recombinant new crown vaccine of the Chen Wei team will end in 6 months.

This is an adenovirus-based recombinant vaccine. Compared to traditional inactivated virus vaccines, it is known as one of the second-generation vaccine technologies.

Recombinant viral vector vaccine refers to the use of viruses as vectors, using genetic engineeringA type of vector vaccine in which a foreign protective antigen gene is inserted into the viral genome and cells are transfected to obtain a recombinant virus, and the corresponding protein of interest is expressed after immunization. A variety of viral vectors including pox virus, adenovirus, and herpes virus (HSV) have been used for vaccine research. Wide, easy to produce high titer virus particles and can accommodate large fragments of foreign genes and other characteristics, has a good application prospects in preventive vaccine vectors.

On this track, the Chen Wei team collaborated with Hong Kong-listed company Conshino on research and development. As early as March, news about Chen Wei’s team preparing the new crown virus vaccine has been circulated.

It is not surprising that the Chen Wei team was able to start clinical trials so quickly. The Chen Wei team has a very strong background in coronavirus vaccines. As early as the end of 2014, Chen Wei and her team developed the world’s first 2014 genotype Ebola vaccine.

Some domestic vaccine developers also believe that Chen Wei’s adenoviral vector vaccine is easier to “run out” than mRNA nucleic acid vaccines. This is because the adenovirus vector is a relatively mature track, and in addition, Academician Chen Wei is the domestic authority on coronavirus.

More importantly, a domestic vaccine researcher believes that the mass production conditions of adenovirus vectors are relatively mature and easy to implement-this is especially important for vaccine production during the epidemic period, and it is also the current outside world’s commitment to the vaccine. One of the reasons for popularity.

A total of 8 national new crown virus key projects have been selected together with Chen Wei’s team, and each vaccine research track has at least 1 ~ 2 projects.

These tracks include Chen Wei ’s team ’s viral vector vaccines, nucleic acid DNA vaccines and mRNA vaccines, as well as traditional inactivated and attenuated vaccines, recombinant protein vaccines, and more. Among the projects selected for nucleic acid DNA vaccines include Ai Weixin (Suzhou) Biopharmaceutical Co., Ltd. team.

The technology route chosen by Ai Weixin is DNA vaccine, which cooperates with American DNA vaccine company Inovio Pharmaceuticals Inc. The vaccine was prepared in the laboratory earlier than other teams.

February 10