On July 12, 2021, Yang Xiaoming was interviewed by this magazine in Beijing. (Reporter Hou Xinying / Photo)
Yang Xiaoming said that experimental and real-world data show that the existing inactivated vaccine still has a good protective effect on the Delta strain, and the public still has to "respond" to the vaccine that has been approved for use, only in this way can we reduce our own risks and the risk of virus transmission in the whole society.
| Author: Feng Qunxing
Since the end of July, there have been imported cases in many places, and the national epidemic situation has shown a multi-point occurrence and local outbreak. The "culprit" that triggered this round of epidemics is the more contagious "Delta" mutant strain that recently raged in Guangdong.
The world is vaccinating, why is the epidemic still repeated? Is the domestic vaccine effective against the Delta strain? With a series of issues that everyone is most concerned about, the global people reporter interviewed Yang Xiaoming, chief scientist of the national "863 Plan" vaccine project and chairman of Sinopharm China Biotechnology Co., Ltd. (hereinafter referred to as China Biologics) - the inactivated vaccine produced by China Biologics is China's first listed new coronavirus vaccine.
Yang Xiaoming told reporters that experimental and real-world data show that the existing inactivated vaccine still has a good protective effect on the Delta strain, and for the vaccine that has been approved for use, the public still has to "respond to it", only in this way can we reduce our own risk and the risk of virus transmission in the whole society. In addition, a new inactivated vaccine specifically for mutant strains such as Delta is also being developed and is progressing well.
"We shouldn't be guinea pigs, do we want someone else to be there?"
In simple terms, inactivated vaccine is to "kill" the virus, but retain its immunogenicity, "dead" virus into the human body, can activate the body's immune response, so that people produce antibodies.
There is a saying in the field of vaccine research and development, "2 billion US dollars in 20 years". It takes at least 8 to 10 years for a vaccine to be developed and marketed. But in the midst of COVID-19, that routine has been broken. Taking China Biologics as an example, it took less than a year from the launch of scientific research to the approval of conditional listing.
Behind such "Chinese speed", there is too much sweat. Yang Xiaoming recalled to the "Global People" reporter that the biggest challenge at that time was "no time to sleep". From the technical route, to whether the animal samples are eaten on time, he must pay close attention to all aspects of vaccine research and development.
Yang Xiaoming has a commemorative trophy on his desk. The wooden base in the lower part reads "Pioneer in the fight against the epidemic with his own body", and the glass picture frame in the upper part is studded with a photo of him collecting blood: the blood in the catheter is flowing, Yang Xiaoming smiles at the camera, and the right hand compares a "V" representing victory.
After receiving the inactivated vaccine, Yang Xiaoming should regularly collect blood for antibody testing. Pictured in April 2020, Yang Xiaoming is collecting blood.
In March 2020, before the launch of phase I and Phase II clinical trials of inactivated vaccines, Yang Xiaoming had been vaccinated as the first volunteer of China Biologics. "We have developed our own vaccines, we dare not vaccinate ourselves, how dare others be assured of vaccination?" We should not be guinea pigs, do we want others to be the ones? ”
Volunteers take regular blood to record antibody data. 1 tube of blood was collected the day before vaccination, and 5 tubes of blood were collected on the third, seventh and fourteenth days after vaccination... At present, Yang Xiaoming has collected nearly 70 tubes of blood, and 1 tube of blood is still collected every month. "It's okay, my skin is thick and easy to recover." He laughed.
In June 2020, phase III clinical trials of inactivated vaccines were transferred to the United Arab Emirates and other countries. There are differences in language, living habits, regulatory rules, social ethics and even working hours in various countries, and Yang Xiaoming has to meet with people from all over the world every day with the time difference: the daytime Beijing time is China, the first half of the night is the United Arab Emirates, and the second half of the night is Peru and Argentina.
In December 2020, the UAE released data on phase III clinical trials of the inactivated vaccine and approved the registration of the vaccine. The data shows that the vaccine protection efficacy is 86%, and there is a neutralizing antibody seroconversion rate of 99%, which can effectively prevent moderate and severe and critical infections. On December 30, the vaccine was approved for conditional marketing in China, becoming the first covid-19 vaccine to be marketed in China.
"In fact, the platform and technology have been researched for seven or eight years"
While racing against the clock to lead the team's research and development, Yang Xiaoming is still planning mass production. "Strain screening, virus inactivation, antigen purification, cell culture, vaccine formulation... In fact, our inactivated vaccine platform and technology have made a number of technological breakthroughs and innovative achievements after seven or eight years of research."
Yang Xiaoming told reporters that before the outbreak, China Biologics has established a new inactivated vaccine process and quality control system, and the production is not a traditional inactivated vaccine, but a "new virus inactivated vaccine".
Various technological breakthroughs are an important reason why China can "be one step ahead" in inactivated vaccines. In cell culture, for example, the new process has led to a significant increase in cell yield. "Just like Mr. Yuan Longping grows rice, other people's homes are 500 kilograms, and our inactivated vaccine is like being able to 'grow 10,000 kilograms'." Otherwise, how can a billion and eight billion vaccines be made? ”
China Biologics is based on the strain of the new coronavirus isolated from the Institute for the Prevention and Control of Viral Diseases of the Chinese Center for Disease Control and Prevention, and borrows its biosafety protection level 3 (hereinafter referred to as P3) laboratory as a research and development site. The two sides have jointly developed a high-titer, genetically stable, immunogenic virus that can be used in vaccine production.
There are also technical thresholds for virus inactivation. Inactivation is not in place, and it will cause disease in the human body; it is excessively extinguished, destroying the antigenic activity of the virus and affecting the effect of the vaccine. In order to "kill" the virus just right, the Chinese biological research and development team designed the "one-step method" and used a new method of inactivation evaluation for the first time; at the same time, through the "one-step column chromatography" large-scale viral antigen purification engineering technology, the comprehensive process efficiency was increased by 125%.
However, everything is in place, and there is still a debt of popularity: the new crown virus is extremely contagious, and the virus leakage will cause biosecurity accidents. Therefore, the production of vaccines is carried out in the P3 workshop. In January 2020, shortly after the vaccine research and development started, Yang Xiaoming notified the Beijing Institute of Biological Products to select a workshop to transform it into a P3 workshop. Wang Hui, then deputy director of the Beijing Institute of Biological Products, quickly selected a workshop and sent instructions: "Do you immediately tear down the original things?" Yang Xiaoming replied: "Wait a day." ”
On this day, Yang Xiaoming will be used to persuade the decision-making team of China Biology. Building a workshop requires an investment of at least 1 billion yuan, and the opposition is not small: China Biology is the "national team" of vaccine research and development, spending taxpayers' money, if the research and development is not successful, the investment has been adrift, who is responsible?
The epidemic was urgent, and Yang Xiaoming made a military order: "I am responsible!" He firmly believes that it is only a matter of time before the development is successful, and for the vaccine to really work and stop the spread of the virus, mass production must be achieved. In the end, the board of directors, the party committee and the president's office of China Biologics unanimously agreed to invest 2 billion yuan in vaccine research and development and production. Yang Xiaoming immediately sent instructions to Wang Hui: Dismantle!
The next day, Yang Xiaoming asked Wang Hui about the progress. "Dismantled?" "Dismantled." "So fast!" "I can't give you time to regret it." After Wang Hui finished speaking, both of them laughed and said in unison: "Broken cauldron sinks the boat!" ”
On May 29, 2020, Yang Xiaoming (first from left) and Liu Jingzhen(second from left), chairman of Sinopharm Group, inspected the P3 production workshop under construction.
With the continuous construction of the P3 workshop, the annual production capacity of China Bio's inactivated covid-19 vaccine has reached 5 billion doses. Yang Xiaoming and team members also cooperated with relevant departments to compile China's first vaccine bio-safety production facility standard and biosecurity system document.
"Those who do scientific research must catch up at any time"
Since being assigned to the Lanzhou Institute of Biological Products of the former Ministry of Health in 1986, Yang Xiaoming has been engaged in vaccine research for 35 years. Behind the childhood memories of the "post-80s" and "post-90s" whooping cough, diphtheria, tetanus vaccine (hereinafter referred to as DTP vaccine) and polio vaccine, there are his research results.
Why go down the path of vaccine research? Yang Xiaoming laughed and said: "The reason is not 'tall' at all." During the college entrance examination, his first choice was to become a pilot, but he mistakenly studied clinical medicine. Later, he was assigned to the Lanzhou Institute of Biological Products and began to study immunology and vaccines.
At the Lanzhou Institute of Biological Products, Yang Xiaoming is mainly involved in the research and development of a new generation of DTP vaccines. DTP vaccine was included in China's immunization program in 1978, but the older generation of vaccine toxicity has high side reactions, more than 70% of vaccinators will have fever, redness and swelling and other side reactions, the public's willingness to vaccinate is not high, affecting the implementation of the national immunization program.
There was also a small episode during this period: one day when he returned home from work, Yang Xiaoming found that his daughter's small arm was as swollen as his fist. "I asked my wife at the time, was the child bitten by a mosquito?" This bag is so big, it is estimated that it is not a mosquito bite, it must be three mosquitoes. As a result, my wife said that the child was vaccinated against DTP today. Yang Xiaoming recalled.
"We made that vaccine." The experience of her daughter's vaccination has further stimulated Yang Xiaoming's determination to tackle the problem. In 1986, he was sent to Japan for short-term training, combined with what he learned during the training, and finally solved a series of technical problems three years later, successfully developing China's first acellular pertussis vaccine, which in turn reduced the side effects of DTP vaccine by 10 to 20 times.
Later, after more than ten years, he established a joint vaccine technology system with the international community. After the increase in dtP VACCINATION rates, the incidence of the three diseases in China has dropped significantly and remained low for a long time.
Polio is also an infectious disease that was once endemic in China and is now almost extinct. Yang Xiaoming told the "Global People" reporter that for a long time, China has faced the problem of mass production of inactivated polio vaccine (hereinafter referred to as IPV), and some of it needs to be imported.
"Before we independently developed IPV, an imported vaccine cost 400 yuan. When we started doing clinical trials, foreign companies adjusted the price to 200 yuan. After our successful research and development and a large number of listings, the domestic vaccine is priced at 35 yuan, and foreign companies adjust it to 38.9 yuan, but we basically do not use their vaccines. Yang Xiaoming recalled to the "Global People" reporter.
"You see, being backward is really going to be beaten. When you don't, its price goes up. When you will, its price will fall. Those who do scientific research must catch up at any time and must not be thrown down. ”
Yang Xiaoming said that now, China's IPV can not only meet the major domestic demand supply, but also export to the world.
"China's advantages ensure the success of vaccine research and development"
Looking back on the past 35 years of scientific research experience, Yang Xiaoming has a lot of feelings. He said that he was a line of work and a line of love, and that if he decided to do something, he "had to do it." Fortunately, he caught up with the era of China's reform, opening up and rapid development, and experienced the "from scratch, from small to large, from weak to strong" in China's vaccine industry.
"In the past, we made vaccines like tofu, pots and pans, jingling. Sometimes there are technical ideas, and there is a lack of instruments and equipment, and it is difficult to push down. ”
Yang Xiaoming still remembers that during the development of the DTP vaccine, the shaker bed in the laboratory was broken, and everyone was reluctant to change it, so they took shifts to shake the relay hand and shake it continuously for 48 hours.
In 1996, Yang Xiaoming was invited to the United States to do research work and stayed for 6 years. During this period, he more deeply felt the gap between China and developed countries. "Once to do an experiment, I told the boss about the research ideas, all the experimental supplies were in place within a week, and I finished all the work in 3 months. This was unthinkable in China at the time. ”
Every day in the United States, Yang Xiaoming watches and learns as much as possible. He made up his mind that he must learn the vaccine technology well and bring it back to China. It was this experience that led him to implement a number of reforms in China Biology.
The more important background is that China has formed an institutional advantage of "concentrating on big things".
"This is China's advantage, which guarantees the success and speed of vaccine research and development." Yang Xiaoming said that the party and the state have always attached great importance to vaccine research and development, as long as the research and development team puts forward the need, "the country must be fully satisfied."
He said frankly that China's vaccines have been "running" for a long time and are currently transitioning from "running and running" to "leading". There is still a gap between China and developed countries, but the research and development of the new crown virus vaccine is a once-in-a-century opportunity for China to overtake in the corner.
At present, China's COVID-19 inactivated vaccine is an "excellent student" in the global anti-epidemic examination.
In February, a new survey released by Nature showed that nearly 90% of scientists believe that the new crown virus will coexist with humans for a long time. Future outbreak trends will largely depend on how people are immunized through vaccinations and how the virus evolves. At present, many countries around the world are also adjusting their strategies. At present, the international epidemic prevention strategy for the new crown virus has changed from "preventing infection" to "preventing severe illness and death".
"According to our research data, the effectiveness of the vaccine against multiple variants still meets the requirements of the World Health Organization." Yang Xiaoming talked about two sets of data -
In the laboratory, by cross-neutralizing the serum of the population that has been vaccinated with the Chinese biological inactivated covid-19 vaccine with multiple new coronavirus variants, it was found that the Chinese biological new crown vaccine can achieve cross-neutralization of four typical variants, including the Delta strain.
On July 20, a real-world protective research report on the effectiveness of China's biological vaccine released by a research institution in Sri Lanka showed that compared with the new crown virus strain circulating in China in the early days, the neutralizing activity of the Chinese biological covid-19 inactivated vaccine against the currently discovered Delta variant was reduced by about 1.38 times (a 32%) decrease, that is, after two injections of inactivated vaccine immunization of Chinese biology, there is still a 68% protection rate for the currently circulating Delta variant.
He said that the next step is to continue to improve the people's willingness to vaccinate. "Without vaccination, the risk you need to bear is certainly higher, and vaccination will greatly reduce the risk of infection and severe illness." China's vaccine is safe, and it is necessary to tell the people about the data and progress in a timely manner. Scientific questions still need scientific answers. ”
In May this year, China Bio's inactivated vaccine passed the World Health Organization's emergency use certification, becoming the first Approved Covid-19 vaccine in China. Up to now, the vaccine has been approved for emergency use or market access in 87 countries, regions and international organizations around the world, and the vaccinated population covers 196 countries, which has run out of China's speed to defeat the new crown epidemic.
Yang Xiaoming said that China Biologics is working hard to implement the important declaration of "taking China's new crown vaccine as a global public good", and contributes China's strength in promoting the process of international cooperation on vaccines and in promoting the construction of a community with a shared future for mankind.
What surprised Yang Xiaoming was that this year, the number of fresh graduates who applied for employment in China Biology exceeded that of previous years by more than 10 times. "Mankind's battle against the new crown virus is not over, and the road to the fight against the disease is even longer. We are very eager for you to join us in the great cause of human health! ”
The journey of China's vaccine is also a sea of stars.