WHO (WHO) held a global research and innovation forum in Geneva on February 11-12. The new coronary pneumonia disease was officially named "COVID-19", which represents the coronavirus disease discovered in 2019.
also addressed the public's eager attention to vaccine issues. WHO Director-General Tan Desai said that the new vaccine for may be completed within 18 months.
As far as the industry average is concerned, the vaccine development cycle takes 5-18 years. From this point of view, 18 months is already "the speed of history."
Behind this, China, the United States, the United Kingdom, Australia... global researchers are intensively spending hundreds of millions of dollars to use new technologies to curb the COVID-19 outbreak at a record speed.
technology assembly! Start the global battle for vaccines
So far, the number of deaths caused by COVID-19 is higher than SARS, which has exceeded 1,000. There are cases in more than 20 countries around the world. The turning point has not yet appeared, and the number of new cases is still increasing. Looking at it from another angle, if COVID-19 does not "come and go in a hurry" like its "close relatives" SARS and MERS, then the vaccine will become the key to victory in this battle.
*SARS: broke out in China at the end of 2002 and basically ended in July 2003; MERS: broke out in the Middle East in September 2012, and basically ended
in 2015. But for a new pathogen, vaccine development cannot be accomplished overnight. The research and development process is roughly divided into three stages: laboratory research, animal experiment and human experiment. Namely laboratory development, pre-clinical research, phase I, II, and III clinical research . This process often takes several years. For example, it took 5 years for the Ebola vaccine to be approved by the FDA in 2014, and the SARS vaccine has not been developed and marketed so far. What
wants to speed up is that needs to abandon the traditional live virus vaccine research and development path, use new technology, and "rush time" with the virus.
① DNA vaccine technology
R&D institution: American biotechnology company Inovio
Inovio is one of the earliest institutions in the world to respond to the new crown epidemic. On January 11, the day after the genome sequence of the new coronavirus was announced, Inovio launched a research and development plan for the new coronavirus, and on the 12th designed a vaccine against the new coronavirus spike protein.
It is worth noting that in a paper in "The Lancet Infectious Diseases", the results of phase 1 clinical trials of the MERS coronavirus DNA vaccine developed by the company have been proved to be safe and effective.
From the development point of view, the DNA vaccines of MERS coronavirus and new coronaviruses are very similar. Therefore, the successful results of MERS clinical trials mean that it is possible to develop DNA vaccines against new coronavirus strains using the same strategy. .
Moreover, this company has accumulated a large amount of safety and immunogenicity data in the MERS vaccine research, which is considered to be the group with the "thickest family" in the research project group.
Currently, Inovio is cooperating with Beijing Aidiweixin Biotechnology Co., Ltd. , and plans to conduct the first phase of clinical trials in China simultaneously. It is reported that the world's latest rapid response technology for nucleic acid vaccines adopted by the two can shorten the development of new vaccines to 1-2 months or less.
②mRNA technology
R&D institution: American biotechnology company Moderna
Different from Inovio, Moderna is a world-leading mRNA technology company, and it already has nine vaccines using the mRNA platform that have entered clinical trials. One of the MERS vaccines is in the stage of animal testing.
will produce a stronger immune response when the spike protein of MERS is in a stable conformation. Therefore, Moderna intends to use the MERS vaccine as the basis to adjust the mRNA accordingly to produce a new vaccine.
Currently, Moderna is manufacturing synthetic mRNA vaccine samples for animal research for National Institutes of Health (NIH) . According to Moderna's prediction, the ideal situation is for the vaccine to perform well in the first phase of the study and be used in human trials 3 months later.
③ Molecular tweezers/opal technology
R&D institution: University of Queensland, Australia
Like the above two technologies, "molecular tweezers" is also a platform method. Aims to produce vaccines against a series of human and animal viruses. The idea is to first synthesize the virus surface protein, which will attach to the cell surface of the host during the infection process, and then clamp them like a pair of pliers, so that the body’s immune system can more easily "start" and eliminate it. Keith Chappell, one of the project leaders and molecular virologist, said that the method has been shown to be effective against other dangerous viruses such as Ebola, MERS or SARS in the laboratory research stage.
Currently, the University of Queensland is cooperating with Ge Lansu SmithKline (GSK) , which provides adjuvant technology to support the University of Queensland's preclinical trials to evaluate the effectiveness of the vaccine. Their goal is to prepare vaccine candidates for human trials in 16 weeks.
In the current stage of research and development, the goal of scientists from all over the world is to find the trigger component that activates the body's defense mechanism. This requires not only time but also funding.
Fortunately, the above three vaccine research and development teams have been supported by the Epidemic Prevention Innovation Alliance (CEPI) with a total of $12.5 million.
In addition, more scientific research teams around the world are racing against time to develop vaccines.
- The new vaccine of Imperial College London has been tested on animals;
- Institut Pasteur, France, is trying to modify the measles vaccine to combat the new coronavirus;
- Johnson & Johnson plans to use adenovirus vector platform and production cell technology to make vaccine candidates ...
China's vaccine progress: the fastest to enter clinical trials in April this year
is the "home field" of COVID-19, China vaccine research and development progress is at the forefront of the world:
- On January 10, Chinese scientists will be the new crown virus The genome sequence was released to the public database;
- On January 24, China announced the isolation of the new coronavirus strain, taking the first step in vaccine development;
- On January 28, Tongji University Affiliated Oriental Hospital and Siwei ( The new coronavirus mRNA vaccine research and development project jointly launched by Shanghai) Biosciences was officially established;
- On February 9, only two weeks after the isolation of the strain, the new vaccine samples have been tested on animals. The technology used by teams above
is the same as that of Moderna. It is an mRNA technology that has emerged in recent years. One of its advantages lies in its fast speed and short preparation time, which is of great significance for emergency epidemics.
Compared with traditional technology, mRNA vaccine is to inject nucleic acid into the human body, so that the components of the vaccine are produced in the human body, and then continuously stimulate the human immune system, just like building a "pharmaceutical factory" in the human body.
▲Using mRNA to guide the synthesis of antigen proteins
Currently, the world's three largest mRNA giants are Moderna in the United States, CureVax in Germany, and BioNTech in Germany. The domestic unicorn is the microbe . These companies have plans for mRNA vaccines.
butFor new technologies, safety and effectiveness are still the biggest challenges for mRNA vaccines. Because up to now, mRNA vaccine therapy has not been fully clinically verified, and there is no official human mRNA vaccine on the market.
It is reported that the fastest progressing mRNA vaccine is the personalized tumor vaccine mRNA-4157 developed by Moderna, which entered phase I clinical trials in December 2017.
is the only company in China that can produce clinical-grade mRNA vaccines in China, and is also one of the first companies to participate in the research and development of new coronavirus vaccines.
According to Sri Lanka Microbiology's prediction, if the animal trials go well, the COVID-19 vaccine they developed will enter human clinical trials as early as April this year.
In addition, according to the China Vaccine Industry Association (CAV), as of February 11, 18 domestic units including China Biology, the Institute of Medical Biology of the Chinese Academy of Medical Sciences, and Kangsino Biology have adopted inactivated vaccines and viral vector vaccines. The development of COVID-19 vaccines has been initiated one after another in different technological paths such as nucleic acid vaccines.
vaccine research and development needs to be changed from passive to active
. Compared with the previous vaccine research and development cycle, the vaccine research and development cycle is often 5-10 years. The current progress can be described by the "speed of light", but despite this, most of the research teams still say "this is still very In the early stage, there are still many steps to take to use people." In other words, the risks and benefits of vaccines are the same. Scientists may fall into the same situation as the SARS outbreak that year-SARS would have disappeared before the vaccine was fully developed. The past epidemics of
were full of such regrets. For example, although the MERS infection is still occurring, there is no commercial vaccine against the MERS virus; the Zika outbreak that caused birth defects has ended when the experimental vaccine was ready for testing. There are two reasons for
:
- One is the speed of vaccine development. If the epidemic declines before the vaccine takes effect, the sample size in the later period will be insufficient, which will make it difficult to advance clinical trials;
- Second is the effectiveness problem. From experimental development to market application, will face various uncertain factors. For example, the effectiveness of the smallpox vaccine is strong, and the smallpox virus can be eliminated; while the influenza virus that is prone to mutation, the vaccine efficiency is only 50%-60%
On the issue of effectiveness, some experts have put forward a more "forward-looking" voice-instead of "catching up" after the outbreak, it is time to explore vaccine prototype designs that can be applied to the entire virus family.
NIH Institute of Allergy and Infectious Diseases, Dr. Barney Graham said, “This way, once new signs of disease appear, the vaccine can be ready for use.”
will prepare the coronavirus vaccine “template” and adjust it accordingly. What we do is to find some unique things that every coronavirus has in common. Scientists at
NIH are considering using Moderna's mRNA vaccine samples to complete this idea.
"If further testing proves that it is indeed effective, we hope that when another coronavirus appears, we can simply switch in a new spike (spike protein, that is, the spike protein of the coronavirus) code to be able to invest. Use."
There is no doubt that the struggle between humans and viruses is long and difficult. Even if the value of the COVID-19 vaccine is not present, it will have far-reaching significance for future disease prevention and control.
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