It has been three months since the first case of Neovirus was diagnosed, and with the outbreak of the disease taking hold worldwide, more and more people are pinning their hopes on vaccine research and development.
In fact, after the Chinese government announced the RNA sequence of the new coronavirus to the world on January 10, various vaccine development and clinical trials have been launched frequently, and many research and development institutions have been "reporting a lot of success". However, in the opinion of many experts and scholars, it is very difficult for a new coronavirus vaccine to play a role in the prevention and control of the outbreak so far and even in the coming months.
Will the boom in the "successful" development of a new vaccine become a "pie in the sky" embarrassment in the current epidemic control task?
Overview of global cases of neo-crown epidemic
Epidemic Map by Dr. Ding Xiang Yuan
New Coronavirus Vaccine Development 'Hits the Spot'
On February 17, the World Health Organization (WHO) said in a statement that it would be 18 months or more before a new vaccine was successfully launched. But apparently, the WHO's judgment has not dampened enthusiasm for vaccine development.
On February 24, the U.S. pharmaceutical company Moderna announced that it had successfully developed a human mRNA vaccine for Neocrown pneumonia in one month and had sent the first batch of vaccine to the U.S. National Institutes of Health to begin safety clinical trials, with plans to test the drug on 20-25 healthy volunteers by the end of April.
The following day, Professor Jinjin Hai's team at Tianjin University's School of Life Sciences announced that it has successfully developed a new oral vaccine for coronavirus, and is now seeking partners to promote the vaccine to the clinic as soon as possible. The vaccine uses food-grade safe brewer's yeast as the carrier and the novel coronavirus S protein as the target for antibody production. It is reported that the vaccine development team, "Professor Jinjinhai himself has taken 4 times the amount of oral samples of the new coronavirus vaccine without any side effects".
On February 26, the Russian Deputy Prime Minister stated that Russia has developed five prototype vaccines for the new coronavirus; on February 27, the Consortium for Epidemic Response Innovation (CEPI) announced that in addition to Moderna, it will fund two other institutions, Inovio and the University of Queensland in Australia, to develop a new coronavirus vaccine.
On February 28, an Israeli research and development organization claimed that they would complete major development of the vaccine within three weeks and that the vaccine was expected to be available as soon as 90 days later
On March 2, President Trump, in a meeting with pharmaceutical company executives and public health officials, called for a new crown vaccine to be developed in a "few months".
In addition, it is known that there are more than 20 SARS-Cov-2 virus vaccine research and development projects underway around the world, and some well-known domestic and foreign pharmaceutical companies have set a "vaccine development" mandate: they hope to develop a successful vaccine within 8 to 12 months, or even 6 to 8 months.
With so much "good news" coming out one after another, people who have been under the shadow of the epidemic for a long time are indeed happy.
However, Marxism tells us that the development of a thing does not only depend on human efforts, but also needs to respect objective laws.
Past scientific research and vaccine development experience always tell us the same thing: vaccine development is a long and rigorous process, and the introduction and application of a new vaccine can never be completed overnight.
Vaccine development process: long and difficult
Generally speaking, successful vaccine development can be divided into the following stages: pre-preparation, post-test validation (animal experiments and phase III clinical trials), registration, marketing, production, and finally putting into use.
The first step is to obtain the source of immunity, that is, to isolate the new coronavirus strain, before entering the vaccine preparation stage. Previously, several institutions in China have successfully isolated strains for drug development and vaccine preparation.
However, the development of a vaccine is only the first step. For the new coronavirus with human cells as the host, researchers are unable to conduct direct research and need to establish an animal model to conduct animal testing and use this model for initial testing of the efficacy and safety of the developed vaccine.
Only after passing the animal model test may a vaccine be declared for preliminary human testing. To conduct human trials, a sufficient number of voluntary volunteers need to be identified, the trial design needs to be reviewed by the ethics committee, and clinical observations can begin only after ensuring that the baseline conditions of the subjects are consistent. Key observations include whether the vaccine can produce antibodies in humans and whether the vaccine can work against the virus after human injection of the new coronavirus.
In addition, clinical trials are not always smooth, and subjects may experience immune overreactivity, or there may be clinical trials that are too long, during which the virus mutates and results in a wasted trial.
After the cumulative phase III clinical trials are completed and the safety, efficacy and stability of the vaccine are fully confirmed, this new vaccine can be applied for approval and registration and finally put into production.
This process may seem simple, but in fact it is very complicated and lengthy. Take Ebola vaccine development as an example, in 2014, a serious Ebola outbreak in West Africa, two years later, the first effective prevention of Ebola virus vaccine development by Canadian researchers developed successfully. It was only in November 2019 that the vaccine was conditionally approved for marketing by the European Commission, five years after the outbreak.
In the case of SARS (2003 outbreak) and MERS (2012 outbreak), which also belong to the coronavirus family and have a high similarity to the new coronavirus strains, no vaccine has been developed to date.
Generally, it takes 2 to 5 years or more to develop a vaccine. In some extreme cases, however, this process can be shortened if researchers from global institutions collaborate, which is why WHO gave an estimate of "18 months and more" in its previous statement.
Even if a vaccine is developed, it will still be in the laboratory stage, and it will take months or even years before it is available and can be used to prevent and control the outbreak.
Professor Zhang Zuofeng, associate dean of the UCLA School of Public Health, told Clove, "Theoretically, a vaccine for the new coronavirus should take at least a few more months. Some research units will probably start animal trials in April, and then human trials will follow, probably until September at the earliest.
mRNA vaccine: actual effectiveness still unclear
Vaccine research and development is currently underway and will soon focus on recombinant protein vaccines, recombinant adenovirus vector vaccines, mRNA vaccines and inactivated vaccines.
Among them, mRNA vaccines are a relatively new vaccine production option.
Unlike traditional vaccine production that requires inactivated viruses or recombinant antigenic proteins, RNA is responsible for protein synthesis in living organisms, so researchers can modify and edit RNA directly, skip the step of synthesizing recombinant proteins or viruses, and inject RNA directly into the body so that somatic cells can produce their own protein antigens.
Moderna is targeting the S proteins (spike proteins) on coronaviruses, which bind to cell surface ACE2 receptors and infect cells. moderna's development strategy is to package the mRNA instructions for the S proteins into lipid nanoparticles and inject the nanoparticles into human muscle to allow the human cells to produce the viral proteins.
Theoretically, this approach allows the body to develop resistance. The mRNA that enters the body is able to further direct the translation of the antigenic protein, which is degraded in the body after the instruction is complete. But theory is theory after all. mRNA vaccine technology has been around since the 1990s and has not replaced the traditional vaccine process because it is very much limited by many factors such as technology and the nature of mRNA itself.
Common vaccines (inactivated viruses or antigenic proteins, etc.) are generally stable and can be administered intravenously to the body, but mRNA itself is very unstable and prone to degradation.
To solve this problem, Moderna is a commonly used method to make mRNA into nanoparticles using techniques such as liposome encapsulation, which can be injected into the body by intramuscular injection. However, it is not known whether these nanoparticles and the mRNA in them will function as expected once they enter the body.
Therefore, although mRNA vaccines can shorten the research and design phase of a vaccine by a considerable amount of time, the actual effect is still unknown. mRNA-1893, a Zika virus vaccine, was successfully developed by Moderna in August 2019, but is still not available.
In addition, no mRNA vaccine has been marketed worldwide to date.
Moderna's production pipeline shows the stage of development of its RNA vaccine (Moderna's website)
It is reported that the company will start a small-scale human trial in March-April, and if the results are positive, a large-scale human trial will follow in June to August. Even if all goes well, the vaccine will not be available until 12 to 18 months later.
MERS vaccine experience unproven, traditional approach difficult to break through bottleneck
In addition to the mRNA vaccine idea, CEPI-funded vaccines developed by Inovio and the University of Queensland in Australia are building on the MERS research to accelerate the development of a new crown vaccine.
The MRES vaccine developed by Inovio is called INO4700, and the vaccine designed for the new coronavirus is INO4800, both of which are DNA vaccines. The company has built a rapid development platform based on its experience with MERS, which has led to the rapid progress in this vaccine development.
The University of Queensland's "molecular clamp" vaccine is essentially a peptide that can be used to maintain the structure of a protein, and the chimeric peptide formed by binding to a viral protein can be purified and used for rapid vaccine preparation. This technology has also been used in the development of vaccines against influenza, Ebola, MERS and other viruses.
Image source: The University of Queensland, Australia
However, no vaccines for infectious diseases have been marketed using this technology, and the feasibility of molecular clamp technology remains to be proven. In addition, no MERS vaccine has been developed to date, so it is prudent to assume that these two new crown vaccines, based on the experience of the MERS vaccine, will be effective.
As for the Israeli research and development organization, which claims to "have a vaccine ready in 90 days," it has been developing a vaccine against infectious bronchitis virus (IBV) for the past four years that has only been proven effective in animal trials.
Although the head of the institute claims to have as many as 53 laboratories, more than 80 doctors and more than 260 researchers on staff. But even if there were 10 or 100 times more researchers, it would still not change the fact that the time necessary for clinical trials has been shortened.
Previously, the Chinese media reported that the Academy of Life Sciences at Tianjin University had developed an oral vaccine for the new coronavirus, using the same traditional vaccine development method, using a brewer's yeast expression system that targets the S proteins (spike proteins) used in the design of the Moderna mRNA vaccine. Some of the new crown vaccines claimed to have been developed in Russia are also theoretically produced using traditional vaccine production processes, so I will not repeat them.
If a bottleneck cannot be broken through technological innovation, it is even more difficult to break through by traditional methods.
Respect the scientific facts and grasp the focus of prevention and control
On the evening of March 3, a picture with the text "The first vaccine shot, academicians try it first" appeared on social networks. The picture was thought to indicate that the vaccine developed by Academician Chen Wei's team had entered the clinical stage, and the caption also said, "The first dose of the new crown vaccine was injected into Academician Chen Wei's left arm today. The first vaccine was injected today into the left arm of Academician Chen Wei. 7 members of the expert team were also injected together.
But soon, the authenticity of the picture was disproved. The micro-blog certified as "Executive Chief Editor of Hong Kong Wen Wei Po Beijing News Center", "Kailai" posted a micro-blog in the early hours of March 4, saying: "This photo circulating is the same shot Chen Wei took before she left for Wuhan, and I took it in 03 (years), aiming to enhance immunity for the battlefield ...... The text on these circulating pictures is incorrect.
At the end of January this year, Chen Wei academician in an interview with China Science News similarly talked about the development of the new crown vaccine: "Vaccine development has inherent cycles and laws, and our understanding of the biological characteristics of this new virus, pathogenesis, transmission mechanisms, susceptible populations, etc., is still very superficial, so the fastest '1 month' to get the vaccine reported on some platforms at present, I think it is unrealistic.
Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said in a media interview, "It is too early for a new coronavirus vaccine to be available, at least not for the next few months, but I believe that an effective drug for novel pneumonia may be available in the near future.
Professor Jiang Shibo, director of the Institute of Pathogenic Microbiology at Fudan University, previously said in a media interview that "all the claims that a successful new coronavirus vaccine has been developed are now ludicrous ...... no vaccine can be used for the prevention of new coronavirus within two or three months.
Professor Ning Yi of Peking University School of Public Health pointed out that the current focus of prevention and control is still to control the source of infection and cut off the transmission route. "Vaccine research and development is very important, but vaccine research and development to control the current outbreak is a pie in the sky, and distant water cannot quench a near thirst. It is not good that people are now turning too much energy to vaccines. Too much attention to vaccines has instead neglected many things in the prevention and control of the current epidemic, including psychological relief and humanistic care for the public and relief workers in the epidemic environment."
As an ordinary person or administrator, we should not pin our hopes on the success of vaccine development, but rather on the prevention and control work and the organized planning of treatment and prevention.
For researchers, the rigor and scientific nature of scientific research should be respected at all times. In China, it has been reported that a researcher even took the vaccine he developed directly himself to show its safety and efficacy. Although this is very humane, it is not scientific and rigorous, and it is extremely dangerous.
For the media, when reporting vaccine-related news, they should not report the good news but not the bad, not only the speed of vaccine development but also the huge challenges behind it, but also respect the scientific facts and ensure the integrity and scientific nature of the news.
Under the epidemic, we need "hope" because "hope" may be the best, but we also need to have enough courage to face the cruel facts before us.
Science is precisely the most powerful weapon to give us hope and courage, and we need to be well
