Since the outbreak of the new crown pneumonia epidemic, many people have been concerned about when relevant vaccines will be available.
This morning, according to Tianjin Cloud, Professor Huang Jinhai’s team of the School of Life Sciences of Tianjin University successfully developed an oral vaccine for the novel coronavirus. Professor Huang Jinhai has taken oral COVID-19 vaccine samples 4 times the amount, without any adverse reactions. For a time, it attracted widespread attention from the society.
As for this latest "research and development" vaccine, most people only pay attention to the written in the title, Tianjin University announced the successful development of the new coronavirus vaccine, and did not pay attention to this vaccine. Animal experiments have not started, let alone human clinical trials have not been conducted. This is what happened to the vaccine? The professor who was in charge of the research and development took it himself in 4 times the amount, which proved that there were no side effects. Times have changed. Vaccines are not Chinese herbal medicines. Professors should not learn from Shennong to taste all herbs. The research and development of modern drugs and vaccines will never be allowed to be used on living people without animal testing.
◆ From research and development to market, it takes at least 10-15 years for vaccines
For Tianjin University's vaccine, an expert with more than ten years of experience in vaccination management at the provincial Center for Disease Control and Prevention, Tao Lina, an expert in the vaccination management of Tianjin University, said: "I doubt whether the new coronavirus vaccine can produce reliable immunity by oral administration. There are many steps from research and development to market for vaccines, such as animal experiments, human experiments, etc. The standardized process should be to end the animal experiments, and drink them again during the I phase of human clinical trials. Now I am a little too hasty."
So, what steps should a vaccine go through from research and development to market?
Vice Chairman of the Shanghai Immunology Society Chu Yiwei said: "Vaccine research and development generally depends on 'years' at the fastest time. If it is an unknown virus, it will take longer."
Chu Yiwei said that the development of vaccines, in layman's terms, is to find a suitable antigen, that is, a piece of protein or peptide, and two conditions must be met: it can not only stimulate the human immune system to respond, but will not cause diseases. But the sequence of the virus is generally very long. It is a very time-consuming task to which segment of protein or peptide can meet these two conditions.
vaccine can usually be divided into inactivated vaccine , live attenuated vaccine, genetically engineered recombinant protein vaccine , nucleic acid vaccine, etc. The research and development of
vaccines has its cycle and scientific rules. According to reports, the preliminary development process of vaccines includes candidate vaccine design, sample preparation, animal immune response testing, animal protective testing, production process and quality standards establishment, preclinical toxicology research and other links. The later development process of vaccines includes applying for clinical practice and conducting clinical trials, and finally the vaccine will be launched.
"Although the development of vaccines generally takes a long time, it still has positive significance in the long run. For example, the new coronavirus is the same as the SARS virus. Previous research experience of SARS virus vaccines may help the development of this vaccine. The successful experience of other vaccines can also be learned from it."
Academician of the Chinese Academy of Sciences Chen Kaixian also introduced that in the early development process of the vaccine, the vaccine must first obtain the immune source, obtain subunits related to live virus isolation, etc., and also conduct immune response tests and animal protection tests, amplify and optimize the production process of the immune source, and do a good job in preclinical toxicological research. Entering the vaccine research and development stage, clinical application needs to be carried out on the basis of preclinical research, and then the vaccine can be launched. In the traditional sense, it takes at least 10-15 years for a vaccine to go to market.
◆Approval is accelerated, and the steps cannot be missing
Experts say that in the current epidemic situation, relevant departments can speed up the approval speed, but the steps required for vaccine development cannot be reduced. For healthy people, in addition to having suitable production processes, the preclinical safety and effectiveness evaluation is very important. In 2014, the Ebola virus broke out in Africa, and it was not until five years later that the first Ebola vaccine was approved in the United States and the European Union.
Why does the vaccine take so long? The classic live attenuated vaccine takes a long time, usually attenuating the virus in the cells and obtaining strains with reduced virility.Live attenuated vaccines are prepared using this strain with reduced virility, which can proliferate in the body and induce the body to produce strong immunity. "But this preparation method may take several months to several years to obtain the attenuated strain. It is difficult to say whether this attenuated strain is safe and induces sufficient protective effect." As for the preparation process, it takes a little shorter time to inactivate vaccines and genetically engineered recombinant protein vaccines.
has a candidate vaccine design, after preparing a sufficient number of samples, animal tests and preclinical evaluation of the vaccine must be completed. If animal tests are progressing smoothly, there must be appropriate processes. This involves the question of whether the production process can be amplified. The quality control methods and standards must go through strict testing procedures before they can be applied for clinical trials. "In general, vaccine development is a long-term process. We have already had influenza vaccines in the past. If influenza caused by a new influenza virus appears, because its protection mechanism is very clear, with mature production processes and quality standards, the research and development of related vaccines will be faster. But if it is an unknown virus, such as the new coronavirus vaccine, it requires more work and takes longer."
◆The laboratory development stage is the "most unreliable" stage
It is understood that the vaccine can be mainly divided into five major stages from research and development to use: R&D stage, registration stage, production stage, circulation stage, and use stage. Among them, the R&D stage is the most difficult step and the most core step. The entire process from getting the virus and starting to develop a vaccine to completing Phase III clinical research can be called the R&D stage. It mainly consists of the following parts: laboratory development, preclinical research, phase I, II, and III clinical research. The laboratory development stage is the "most unreliable" stage. You must repeatedly modify the process and test results to get the desired vaccine.
Currently, China's research on the new coronavirus vaccine has basically reached the stage of preclinical research. This stage of research is mainly conducted on animals, such as guinea pigs, rabbits, and even primates closest to humans. At this stage, many attack experiments and control group experiments are required to observe the production of antibodies, the possible pathological reactions to the human body, and the side effects of long-term use on the human body.
How should the preclinical research stage be carried out and what should be paid attention to? An old virologist and vaccine development expert interviewed said: First of all, the source of respiratory infectious diseases cannot be vaccinated through the digestive tract. Secondly, it is illegal to directly experiment on humans without animal experiments and without State Food and Drug Administration (FDA). No matter how urgent the demand for vaccines is, the scientific attitude and legal concepts in vaccine research cannot be missing.
The virologist said that it is very unscientific to declare the vaccine successful without conducting a drug test. Animal experiments are required in vaccine development, and the purpose is to observe the allergic reactions, pathological reactions, and long-term toxic effects of the vaccine through animal challenge experiments. Some vaccines may have side effects such as immunopathological reactions, severe pneumonia, myocarditis, muscle atrophy, and nerve cell dehydration. At the same time, the control group is also needed. The commonly used animals at this stage are rhesus monkeys . The rhesus monkeys are used to test the protective effect and safety of the vaccine, verify its long-term carcinogenicity, etc. Data from the drug challenge experiment must be taken out before the FDA can be applied for clinical trials.
◆Why coronavirus vaccine products have been produced in 17 years?
After the outbreak of the new crown pneumonia epidemic, people keep asking: Since the outbreak of SARS in 2003, the coronavirus has attacked humans three times, and each time has brought great pain to humans. But to this day, why have we not completed the coronavirus vaccine product for clinical trials? Many experts and scholars expressed similar views: the development of major infectious vaccines is sometimes quite long, unpredictable and expensive. Its birth not only requires the efforts of scientists, but also requires the support of the government, and requires large investors and pharmaceutical factories to take over. If the virus no longer spreads, the vaccine will lose its commercial significance and companies will have no motivation to invest.Li Hangwen said that when Si Microbiology first decided to invest in the development of the new coronavirus vaccine, shareholders opposed it. As the epidemic becomes more and more serious, investors' attitudes have begun to turn to support, and some investors have even proposed to add the next round of investment.
The considerations in this article do not entirely come from the evaluation of commercial value, but include the recognition of corporate social responsibility. In the 17 years since 2003, the world has undergone earth-shaking changes. With the advancement of technology, biopharmaceutical companies have stronger financial strength and talent reserves. After the SARS outbreak, it took about 17 months for researchers to start human trials. Now, the developers of the new coronavirus vaccine hope to shorten the time to three months. It turns out that different types of coronaviruses have never been far away from us. Whenever a major outbreak is encountered, the government’s primary focus is on establishing physical barriers, such as blocking internal cities or intercity traffic to prevent the spread of the disease.
But in the eyes of medical experts, the best way to change the rules of the game may be to identify the virus and find vaccines and drugs to solve it. "Even if it is only one in ten thousand possible, we have to put in 100% of our efforts to try. This is the charm of scientific research." Dr. Qian Tianyi, School of Medicine, Tsinghua University, said that although the vaccine may not solve the disease that I wanted to solve at the time, the continuous accumulation of cognition will be helpful for subsequent research and development. Perhaps, this is the significance of vaccine development. Without vaccines, humans can only make passive defenses; with vaccines, humans have the opportunity to take the initiative. (Source: Jiefang Daily Huang Haihua/Text, Beijing News Wang Kala/Text, Finance, Yicai.com)
