Shanghai to develop new coronary human-derived cell vaccine Scientists have tested the first needle

Shanghai scientists have made a unique attempt to explore the safer human-derived cell carrier vaccine, and completed the first injection for this purpose. But the immune effect of the human-derived cell vaccine, and its ultimate success, remains a challenge. To deal with the epidemic to science and technology to answer, to the method. Since the outbreak of new coronary pneumonia, China’s scientific research team has set up a special vaccine research and development course, along five technical routes to steadily promote the work of vaccine attack.

Shanghai to develop new coronary human-derived cell vaccine Scientists have tested the first needle

In addition to these five technical routes, Shanghai scientists have made a unique attempt to explore the safer human-derived cell carrier vaccine and completed the first injection. But industry insiders say the immune effect soutcomes of the human-derived cell vaccine and its ultimate success remain challenges.

The animal trials are now in their advanced stages, and if preliminary data show good results, the expected vaccine will soon be pushed to clinical trials.

New global vaccine platform

On February 26th Xu Jianqing, a researcher at the Shanghai Public Health Clinical Center, gave himself a new coronanucleic acid (DNA) vaccine, and about two weeks later, he will receive a second dose. Xu Jianqing told the first financial reporter, the second needle vaccine is a bit special, this is the world’s first human-derived cell-based vaccine.

Xu Jianqing is the director of the Institute of New Hair and Reproduction Infectious Diseases at the Shanghai Public Health Clinical Center and the main person in charge of the agency’s new crown vaccine team. Starting in January 2020, his team will begin the simultaneous development of nucleic acid vaccines, human-derived cell vector vaccines, and nanoparticle vaccines. Today, nucleic acid vaccines have been tested in mice, animal trials are under way for primates, and human-derived cell vector vaccines have been successfully prepared.

In an exclusive interview with First Financial, Xu said his team had developed about 10 vaccines. According to the animal test design, in the first round of vaccine screening, the mice have completed all two injections, the preliminary results show good results. On February 18, researchers injected the first dose of the vaccine into monkeys in a second round of parallel control trials, and a second human-derived cell vaccine will be injected in the coming week, according to preliminary results from the mouse trial.

“The role of the first vaccine is to stimulate the body’s immunity, the equivalent of the body’s immune system to get a preliminary understanding of the virus, but has not yet formed a very deep impression, the second vaccine to strengthen the role of immunity, is more targeted to stimulate the body’s neutral and protective antibodies.” Xu Jianqing told the first financial reporter.

Unlike the existing technology development path of traditional vaccines, Xu Jianqing chose a vaccine development method he had envisioned 20 years ago, with human-derived cells as a carrier, the virus’s S protein is expressed on the human cell membrane, which can greatly improve the safety of the vaccine.

This method attempts to express the virus surface echidna protein on the human cell membrane, the principle does not seem to be complicated. “On the one hand, this method retains an effective target for the formation of antibodies to the virus, while avoiding the pathogenicity of the virus itself, and achieving a speed, safety and efficiency in general. Xu Jianqing told the first financial reporter, “Human-derived cell vaccine development faster than inactivated vaccine research and development, and nucleic acid vaccine development speed is comparable, because there is no need to isolate the virus and virus amplification.” “

The technical route of traditional vaccine development includes inactivated vaccines and virus-reducing virus vaccines, which are generally amplified in cells and further purified until the vaccine contains only the required viral ingredients, but in these steps, the virus is active and may be at risk of disease. And in the process of adding substances such as adjunos, it also increases the risk of possible harm to human health.

For human-derived cell vector vaccines, the risks in the development of traditional vaccines can be eliminated, because the vector itself comes from human cells. Xu Jianqing told First Financial Reporter: “Our vaccine vector comes from the human body’s own cells, not infectious, more safe than the virus.” It can also be modified with new genetic engineering techniques for its prototyping proteins, which are difficult to achieve with traditional inactivated and detoxified vaccines. “

On the other hand, human-derived cells as a carrier, not only can express the protein of the virus, but also can express some of the human body’s cytokines, combined with a specific inactivation method, can eliminate the use of adjuno, is expected to the elderly can also achieve a strong protective effect. “This is also very difficult to achieve on the platform of other vaccines at the moment. Xu Jianqing told the first financial reporter.

The plan started five years ago.

At present, more than 20 vaccine development platforms around the world, has not seen the emergence of this human-derived cell vector vaccine. But scientists told First Financial that many laboratories have a way to implement the technology.

“It’s a very interesting way to simulate viral particles,” Paul McKay, an immunologist at Imperial College of Technology, told First Finance. Let human cells express coronavirus protein and add it to the surface of human cells. Our labs and many others can do the same. But it’s not necessarily successful to simply inject human cells that express viral proteins directly into the body. “

Prof McKay says human cells also have many other proteins, so this approach may not stimulate the body’s high level of immune response. But Professor Xu Jianqing told First Financial That his team had applied this method to the development of influenza vaccines and AIDS vaccines about five years ago, and had been tested in primates, and the immune response was initially validated.

“If this is a very classic way of expressing and purifying the S protein in human cells,” Professor Frederic Tangy, director of the Vaccine Innovation Laboratory at the Pasteur Institute in France, told First Minister. But does the body immune produce a rejection reaction? Traditional methods of avoiding exclusion are generally using hamster cells and adding adjuas. “

Professor Tang ji also suggested that the S protein is a high-quality immunogenic, can effectively induce neutralizing antibodies, so the S protein’s triophysical conformation is also an important issue. In this regard, Xu Jianqing to the first financial reporter said: “the membrane protein of the virus in the human cell membrane expression and on the virus membrane is the same, spatial structure is consistent, there will be no lack of effectiveness.” “

Since this human-derived cell vaccine has not been clinically proven, the safety and effectiveness of the human immune response is still to be verified. “This new coronary pneumonia provides us with an important opportunity to accelerate clinical trials. Xu Jianqing told First Financial Reporter.

At a press conference held on March 6th by the State Council’s Joint Defense and Control Mechanism, Zheng Zhongwei, director of the National Health and Development Center, said that by April, some vaccines in China are expected to enter clinical research or emergency use. In this regard, Xu Jianqing told the first financial reporter: “From the speed of expansion, in April can complete the pilot production, there is a chance to enter clinical research.” “

Human-derived cell vaccine, if successfully developed, will also become the world’s first, which is a major innovation in China’s technology. Xu Jianqing told the first financial reporter: “If in the development of this new crown vaccine, or stick to the stereotypes, follow the old way, then will miss an excellent opportunity for scientific research.” “

But before there is enough data to prove that the vaccine is effective, Xu’s team still needs to continuously screen and improve the vaccine’s ingredients and methods through animal trials. According to Xu Jianqing’s vision, he hopes to replace the complete S protein by activating the body’s neutralizing antibodies using only the receptor binding region RBD protein in the S protein. But there is still not enough data to support their decision.

“Previous studies suggest that antibodies in non-RBD areas can be harmful and can form antibody-dependent disease-causing exacerbations. Ideally, only RBD is used as a target to induce neutralizing antibodies, which is also more beneficial to older patients. If not, it is possible to extend the target range to the entire S protein. Xu Jianqing told First Financial Reporter. His team is currently closely monitoring the experimental data.

Three-week capacity of up to 500,000

Will this human-derived cell vaccine pioneered by Xu Jianqing’s team be successfully commercialized? In his view, the most important work at present is to build a new production facility platform with human-derived cell vectors. “As long as the platform is built, the production process as soon as possible to verify, the latter can be fully in accordance with the mature production process to go.” Xu Jianqing told First Financial Reporter.

The construction of new platforms is critical to the future of developing vaccines for other diseases in the same way. Xu Jianqing told first financial reporters: “We are hoping to turn human-derived cell vectors into a brand-new platform to promote the accelerated development of the entire vaccine technology.” Later, another immunogenic can be done to develop other vaccines, also very quickly, rather than just for coronaviruses. “

Although no one has previousexperience in the commercialization of source cell vaccines, Xu Jianqing has learned through exchanges with some vaccine manufacturers that the current process of vaccines from transportation logistics to preparation preservation methods has developed quite maturely. “I was worried about the vaccine preservation liquid, but it doesn’t seem to be very big, these manufacturers have technical reserves. Xu Jianqing told First Financial Reporter. He expressed the hope that the subsequent reduction in production time as much as possible to make up for the delays that the process might delay.

Xu Jianqing said that the production cost of human-derived cell vaccines is lower than that of inactivated vaccines, nucleic acid vaccines and other vaccines. And nucleic acid vaccines may face greater production challenges.

He told First Financial reporter, because the human-derived cell vaccine only need to do cell amplification, eliminating the virus vaccination, amplification and purification steps, so production will be faster. The team also considered inactivating with high-energy rays, without contamination of the vaccine.

At present, Xu Jianqing team has been docking with downstream manufacturers. He predicts that the three-week vaccine could produce at least 5-100,000 copies.

According to the official announcement of the China Vaccine Association, 18 member institutions, including the Institute of Medical Biology of the Chinese Academy of Medical Sciences, Kangsino Bioco, Beijing Kexing Biological Products Co., Ltd., are currently carrying out research and development of new crown vaccines, involving medical research institutions, state-owned enterprises and private enterprises. These include nearly 10 listed companies whose technical routes include inactivated vaccines, recombinant genetically engineered vaccines, adenovirus vector vaccines, nucleic acid vaccines, and vaccine vector vaccines for detoxified influenza viruses.

“Clinical trials and approval of vaccines take time, and there is a very real problem that, like SARS vaccines, if the outbreak is over before clinical trials are conducted, then three-stage clinical trials will be difficult to carry out again,” Jin Man, a researcher at the Shanghai Public Health Clinical Center, told first financial reporters. Despite this, Kim believes it is important to lay the foundation for science.

Many countries around the world are also actively involved in the development of the new coronary pneumonia vaccine, including projects in cooperation with relevant Chinese institutions. On February 28th World Health Organization Director-General David Tan said more than 20 new coronary pneumonia vaccines were currently being developed around the world, and some treatments were undergoing clinical trials with the first results expected within weeks.