The mRNA vaccine of nucleic acid vaccine is the first to enter the clinical trial stage.

In March 16th, the new US crown virus vaccine started the first phase clinical trial. The first patient received the experimental vaccine on the same day.

The mRNA-1273 vaccine was developed by the National Institute of allergy and infectious diseases (NIH) of the National Institutes of Health (NIAID) and Moderna Inc., funded by the National Institutes of health. 45 healthy volunteers, aged between 18 and 55, will participate in the clinical trial of the vaccine at Kaiser medical group, KPWHRI, Seattle, and will undergo a one year observation after two rounds of vaccination.

However, Anthony Fauci of Changan, the National Institute of allergy and infectious diseases, has said that even if the initial safety test is progressing smoothly, it will take a year to a year and a half for its large-scale application.

So far, the mRNA new crown vaccine has been "the top priority" in the development of multiple vaccines, and has entered the human clinical trial stage. The mRNA-1273 vaccine has not been tested in new animals.

Although the development of mRNA vaccine is relatively fast, safety needs to be focused. Traditional inactivated vaccines are still mainstream and more secure. The vaccine industry told the twenty-first Century economic news reporter: "although it seems that the vaccine will still take a long time to come out, the importance of research and development as a strategic reserve is very important."

"MRNA" vaccine

At present, the research and development of the new crown vaccine all over the world take the 5 technical routes of inactivated vaccine, genetically engineered recombinant subunit vaccine, adenovirus vector vaccine, attenuated influenza virus vector vaccine and nucleic acid vaccine. The mRNA vaccine is one of the nucleic acid vaccines.

In the history of human vaccine, the mRNA vaccine can be regarded as the "younger generation".

It was not until the early 90s of last century that human beings first discovered that mRNA injected into mice could express activity, produce related proteins, and form immune response, which is the rudiment of mRNA therapy. However, mRNA technology was not applied to the human body rapidly until the twenty-first Century. With the development of mRNA synthesis, modification technology and delivery technology, mRNA therapy has returned to the view of biopharmaceutical companies. At present, the mRNA vaccine is mainly used in the two fields of infectious diseases and cancer.

Compared with inactivated vaccine, recombinant protein vaccine and other traditional vaccines, the production cycle of mRNA vaccine is shorter, which is also an important reason why it can get the top priority. MRNA is a nucleic acid molecule carrying genetic information. It is an intermediate step involved in DNA transcription and protein production. Traditional vaccines have long production cycles because they have to synthesize proteins. The mRNA vaccine can be used to synthesize mRNA, which translates antigen into the body in vitro. It can be delivered directly to the body, and can be transferred from the cells in vivo to an antigen protein that stimulates the immune response. The activated immune system can resist the invading virus.

In short, the mRNA vaccine is equivalent to forming a "pharmaceutical factory" in the human body. It does not need to directly use pathogens, nor does it involve the cultivation and fermentation of target cells. This also makes mRNA vaccines faster and more standardized.

At the same time, compared with the traditional peptide and DNA vaccine, the mRNA vaccine itself does not cause safety problems. It does not insert gene mutations and can be degraded by cells. All these advantages make mRNA vaccine a high expectation.

However, as a relatively new technology, the safety of mRNA vaccine delivery platform is very important.

The so-called delivery platform is the "shell" wrapped outside the mRNA, which allows the fake virus to enter the body through the fusion of the "shell" and the cell membrane. Yu Dongceng, GSK's antigen identification and pre clinical research and development director of molecular biology, said that the key issue of mRNA is safety. The patented technology of each research and development team's delivery platform is different.

Although most of the clinical studies of mRNA vaccines are no problem at present, there are indeed some examples of side effects, including some serious side effects, resulting in injection sites or systemic reactions. In addition to potential side effects, some clinical studies have shown that the efficacy of mRNA vaccine in humans is much lower than that in moving objects.

Professor Pasteur Frederic Tangy, director of the vaccine innovation laboratory at the Institute of research, Pasteur, said that although mRNA developed vaccines quickly, the current method has not been clinically validated, and the industrial manufacturing process is far from mature, unable to produce tens of millions of vaccine preparations required.

What is more noteworthy is that the new crown virus vaccine developed by the US company Moderna is not entirely new. It is a nucleic acid vaccine (mRNA-1273) developed for MERS before. The reason why the I phase of clinical trials is so quick is that the vaccine did not use the new crown virus samples, but instead modified the old vaccine and submitted it to the National College of medicine in late February. There was no animal test before the clinical trial (original version of the vaccine was done), and the vaccine did not use the new crown virus sample, which was safe or guaranteed, but the effect was huge uncertainty.

International competition for vaccine research and development

With the new crown pneumonia epidemic sweeping the globe, the appeal for the new crown vaccine is becoming more intense. At present, many countries and institutions have joined the vaccine research and development competition.

In February 29th, WHO released 31 vaccine candidates for the new crown virus (including three mRNA vaccines). At present, these vaccine research and development projects vary.

In China, a number of enterprises, including China Health Group, Hua Lan bio, Zhi Fei bio, Beijing Kexing, Liaoning Cheng Da, Kangtai biology, Conchino biology, Watson biology, Fosun medicine and so on, have carried out vaccine research and development from 5 technical routes: inactivated vaccine, genetically engineered recombinant subunit vaccine, adenovirus vector vaccine, attenuated influenza virus vector vaccine and nucleic acid vaccine.

Internationally, large pharmaceutical companies including mod, CureVac and other innovative companies, such as Sanofi, GlaxoSmithKline and Johnson, have also invested in the development of new crown vaccine. Among them, mRNA and DNA vaccines have been developed relatively fast. Some companies have basically completed research and development and animal testing. They plan to conduct clinical trials in late March and April.

It is noteworthy that universities and research institutes have also become the main force in the development of new crown vaccine in China. In March 17th, Lei Zhaozi, director of the science and Technology Department of the Ministry of education, said at the press conference of the joint defense and joint control mechanism of the State Council, with the support of the scientific and technological research group, the Ministry of education began to mobilize research teams from Xiamen University, Sichuan University, Tsinghua University, Peking University, and Peking University from the beginning of the Spring Festival, focusing on influenza virus vector vaccine, recombinant protein vaccine and nucleic acid vaccine three We will push forward the development of new crown pneumonia vaccine in collaboration with research institutes and related enterprises.

In addition, colleges and universities have isolated antibodies against new coronavirus with high and active antibodies from the blood of patients with new crown pneumonia. The high purity and whole human neutralizing antibody prepared by this method can provide short-term immune protection for about three weeks, and is preparing for animal protection test.

At the above press conference, Wang Junzhi, academician of the Chinese Academy of engineering, also said that as of now, the vaccines in the five major technological directions have been progressing smoothly. The first batch of 9 tasks have already completed most of the work of pre clinical research (animal effectiveness and safety studies). Most of the research and development teams have completed pre clinical studies in April and have started clinical trials step by step. He said that some of the research and development units that had made relatively rapid progress had submitted clinical trial application materials to the State Administration of drug supervision, and carried out clinical trial plan demonstration, recruitment of volunteers and other related work.

But he also pointed out that there are strict laws, regulations and technical standards for the listing of vaccines at home and abroad. When the vaccine enters clinical trials, pharmaceutical research, effectiveness study and safety study must be completed. At present, Chinese scientists in the field of vaccines are in line with relevant regulations and technical requirements. On the one hand, they strive to seize every minute and every minute. On the one hand, they adhere to the scientific laws and ensure the safety and effectiveness of vaccines, so as to accelerate the research and application of vaccines.

The research and development of vaccines should also follow the law. It takes 5-10 years to complete the three phase of the vaccine trial, and to face many variables in the human trials. In particular, phase III clinical trials are designed to comprehensively assess the efficacy and safety of vaccines, requiring thousands to tens of thousands of subjects. This means that the vaccine must catch up with the epidemic before it can become a reality. This is also one of the important reasons why the SARS vaccine that has entered the first phase of human trials in 2003 has not yet completed clinical trials. At the same time, if the new crown virus is mutated, whether the original vaccine is still effective and safe, it needs to be revalidated. Even if the laboratory can complete the research and development of the new crown vaccine in a short time, it is still a long way to go to develop a practical vaccine successfully.

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