Novel coronavirus vaccine: where is the new recombinant protein vaccine for three injections?

The first batch of recombinant new coronal vaccine has been widely used in Heilongjiang Science Popularization Center, and the situation of “three arrows” has been formed in China

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Why develop this kind of vaccine? What are the characteristics of vaccination procedure? In April 24th, the new vaccine of recombinant human genome of the National Biological Research Institute of China Pharmaceutical Group launched phase I / II clinical trial in Shangqiu, Henan

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The safety, tolerance and immunogenicity of different doses of recombinant New Coronavirus vaccine (CHO cells) after vaccination in healthy people aged 3 and above were evaluated

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On April 25, the first injection of the clinical trial was successfully completed in Ningling County, Shangqiu City, Henan Province

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Before that, the recombinant new coronavirus vaccine jointly developed by Institute of Microbiology, Chinese Academy of Sciences and zhifeilongkema company was approved for emergency use in China on March 10

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Since April, it has been put into use in many provinces and cities in China, becoming another new coronavirus vaccine for open vaccination

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This is also the first new coronavirus recombinant subunit protein vaccine approved for clinical use in the world

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In early April, the recombinant new coronavirus vaccine was put into use in Jiangsu Province (photo source: Jiangsu Radio and television station)

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So far, three of China’s five vaccine R & D technology routes have been open for vaccination: first, inactivated vaccines, including three inactivated vaccines produced by Sinopharm Beijing company, Sinopharm Wuhan company and Beijing Kexing Zhongwei company; The second is adenovirus vector vaccine, which is type 5 adenovirus vector vaccine produced by Tianjin kangxinuo company; The three is recombinant protein vaccine for recombinant New Coronavirus vaccine (CHO cells)

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At present, there are two kinds of inactivated and adenovirus vector vaccines on the market

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Why use the third kind of vaccine? Can different kinds of vaccines be mixed? The most safe recombinant protein vaccine is a specific protein of new coronavirus directly produced by bioengineering technology

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These proteins can train the human immune system to recognize new coronavirus and produce corresponding antibodies

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In fact, the relevant research and development technologies have been verified in practice in various mature vaccines, such as hepatitis B vaccine with 30 years of production and use experience, cervical cancer vaccine, recombinant protein influenza vaccine, hepatitis E vaccine, recombinant protein herpes zoster vaccine, etc

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The official account of the world’s first recombinant protein vaccine (photo source: “I am a scientist iScientist” WeChat public) Wang Xinquan, Professor of life science, Tsinghua University, told an interview with our reporter: at present, there are differences in the R & D technology between the recombinant protein vaccine approved for emergency use and the two vaccines approved before listing

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But all of them use virus antigen to induce human immune system to produce corresponding antibodies to resist potential new coronavirus infection

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It is understood that the new coronal recombinant protein vaccine has completed two clinical trials in the Second Affiliated Hospital of Chongqing Medical University, Beijing Chaoyang Hospital of Capital Medical University and Xiangtan CDC of Hunan Province

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The evaluation results of these trials show that the vaccine has good human tolerance and immunogenicity

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In addition, the vaccine is being carried out in Uzbekistan, Indonesia, Pakistan and Ecuador in an international multi center phase III clinical trial, and was approved for registration in Uzbekistan on March 1 this year, becoming the first new coronal recombinant protein vaccine approved for use in the world

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Ye Sheng, Professor of Beijing University of Aeronautics and Astronautics and Secretary General of the Science Popularization Committee of the Chinese Biophysical Society, explained to reporters that the production process of the recombinant protein vaccine does not involve a complete new coronavirus, and even does not need any virus as a vector, so it is the highest in safety

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In the production workshop of Xinguan inactivated vaccine of Beijing Institute of biological products, the well-dressed staff are operating the equipment (photo source: website of the Central Commission for Discipline Inspection and the State Supervision Commission)

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The existing clinical trial results also show that the vaccine has good safety and effectiveness, and most of the subjects have no adverse reactions, The adverse reactions of very few subjects were mild or moderate

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The vaccine has also been studied in older people

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Although the neutralizing antibody level of the elderly is lower than that of the young adults, it is still within the effective range

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Therefore, the recombinant protein vaccine is approved for people over 18 years old, including the elderly

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Why is the recombinant vaccine “late”? Recombinant protein vaccine is safer

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Why is the research and development speed slower than inactivated vaccine and adenovirus vector vaccine? Ye Sheng believes that this is mainly due to the difficulty of its research

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It takes a long time to select which protein on the virus and which part of the protein can produce the most effective immunity

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At present, this new coronavirus recombinant protein vaccine uses the receptor binding region (RBD) of spike protein (s protein) on the surface of new coronavirus prepared by DNA recombination technology, which is equivalent to a small component of the virus (so this kind of vaccine is also called “recombinant subunit vaccine”)

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The Institute of Microbiology of Chinese Academy of Sciences has contributed the key patent technology of “RBD protein dimer”

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Compared with RBD protein monomer, RBD dimer can increase the level of neutralizing antibody dozens of times (original picture: cells)

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Although this vaccine comes late, it has its advantages in production

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Zhang Yuntao, chief scientist and vice president of Sinopharm China biology, previously pointed out in an interview: recombinant vaccine integrates the most effective antigen components of inactivated vaccine into the system

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In the whole process of preparation, it does not involve live virus and other infectious materials, so it does not need large-scale and high-level biosafety production facilities, and can achieve high yield, high purity and high-quality production Low cost production

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The storage environment of this recombinant protein vaccine is 2 ℃ ~ 8 ℃, which is similar to other vaccines, but its actual thermal stability should be higher

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The same kind of hepatitis B vaccine can still be inoculated at 37 ℃ for 30 days

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Why three injections? At present, the vaccination times and interval of various new coronal vaccines on the market in China are different, such as two injections of inactivated vaccine and one injection of adenovirus vector vaccine

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According to the national technical guidelines for new coronavirus vaccination (First Edition), three doses of recombinant new coronavirus vaccine were inoculated; It is suggested that the interval between the two adjacent doses should be more than 4 weeks, the second dose should be completed within 8 weeks after the first dose, and the third dose should be completed within 6 months after the first dose

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(photo source: People’s daily) Ye Sheng explained that in principle, adenovirus vector vaccine can produce large quantities of virus protein in human body with the help of human cells, so one injection is enough to produce enough immune response; Inactivated virus can not propagate in human body, so it needs two injections

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The first dose can stimulate the body to produce partial immune response, while the second dose can produce better immune effect

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In contrast, the recombinant protein vaccine is not a complete virus, and our immune system will not regard these small proteins as a major threat, but through several repeated vaccinations, our immune memory can be strengthened, so that we have the ability of immune protection

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The specific vaccination times and program are determined according to the results of previous clinical studies

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According to the published research data, at the end of December last year, in the phase I / II clinical trial of the vaccine, a trial scheme with doses of 25 μ g and 50 μ g and vaccination procedures of 2 and 3 doses was designed

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The results of clinical trials showed that 25 micrograms × The effect of 3 doses is better.

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