October 3, 2022

Medical Trend

Medical News and Medical Resources

COVID-19 Vaccines Development Progress

COVID-19 Vaccines Development Progress

The new coronavirus  (COVID-19) vaccine is a vaccine against the new coronavirus. On January 24, 2020, the Chinese Center for Disease Control and Prevention successfully isolated China’s first strain of new coronavirus. At 20:18 on March 16, the recombinant COVID-19 vaccine was approved to start clinical trials. On April 13, China’s new coronavirus vaccine entered phase II clinical trials. On August 20th, the clinical trial of China’s bio-COVID-19 inactivated vaccine under the Sinopharm Group was launched in Peru (Phase III). On October 8, China signed an agreement with the Global Alliance for Vaccines and Immunization to formally join the “COVID-19 Pneumonia Vaccine Implementation Plan.”

As of October 20, 2020, China has vaccinated a total of about 60,000 subjects, and no serious adverse reactions have been reported.

COVID-19 Vaccines Development Progress

1. R & D process editor

The general process and cycle of vaccine research and development include two stages:

The first stage is the pre-vaccine development process, including obtaining immunogens (obtaining live viruses, isolating related subunits, obtaining recombinant proteins through genetic recombination technology or synthesizing related DNA (RNA)), immune response testing, animal protection testing, and immunization The original production process (amplification) optimization, pre-clinical toxicological research and other links.

The second stage is the vaccine development and registration process, including pre-clinical research, clinical application, and clinical trials, and finally the vaccine can be marketed. [3][4]

2. Research and development

As of June 27, 2020, there are more than 200 vaccine candidates worldwide, 15 of which are undergoing human clinical trials. [5]

On July 20, 2020, there are currently about 250 candidate new coronavirus vaccines in development worldwide, of which at least 17 vaccines are in clinical trials [6].

China

On January 24, the Chinese Center for Disease Control and Prevention has successfully isolated China’s first strain of the new coronavirus. The National Pathogenic Microorganism Resource Bank released the virus species information and electron micrographs of this virus (New Coronavirus Wuhan Strain 01), as well as important authoritative information such as the nucleic acid detection primers and probe sequences of the novel coronavirus. These have laid the foundation for the development of vaccines. [7]

On January 26, Xu Wenbo, director of the Institute of Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, said that the center has started the research and development of a new coronavirus vaccine, has successfully isolated the virus, and is screening seed strains. [8]

On January 28, it was learned from the Oriental Hospital Affiliated to Tongji University that the translational medicine platform of the Oriental Hospital Affiliated to Tongji University cooperated with Siwei (Shanghai) Biotechnology Co., Ltd., relying on the “Shanghai Zhangjiang National Independent Innovation Demonstration Zone Stem Cell Strategy Bank and the clinical transformation of stem cell technology” The sub-task of the “Platform” project-the results of the mRNA synthesis platform, quickly promote the research and development of new coronavirus mRNA vaccines. The project has been urgently completed for registration.

On February 15, in accordance with the decision and deployment of the Party Central Committee, under the leadership of the Central Leading Group for Response to the Epidemic and the Joint Prevention and Control Mechanism of the State Council, the scientific research team set out to deploy vaccine research and development tasks. The vaccine research and development class under the scientific research team was established.

It was reported on February 26 that the Fujian Provincial Department of Science and Technology established a project to support the “Research on New Coronavirus Candidate Vaccines and Quality Control Methods” project of Xiamen University, to develop COVID-19 pneumonia vaccines from two technical routes of attenuated vector vaccines and genetic engineering recombinant vaccines. [9]

On March 17, Wang Junzhi, an academician of the Chinese Academy of Engineering, said at a press conference of the Joint Prevention and Control Mechanism of the State Council that China is carrying out emergency development of the COVID-19 vaccine in accordance with five technological routes. [10]

On March 18, Zhong Nanshan, the leader of the high-level expert group of the National Health Commission and academician of the Chinese Academy of Engineering, said at the Guangzhou epidemic prevention and control conference that the Chinese COVID-19 pneumonia vaccine has passed animal experiments and will be used in human clinical trials. [11]

On March 21, according to public information on the China Clinical Trial Registration Center, the sponsors of the trial were the Institute of Bioengineering of the Academy of Medical Sciences of the Academy of Military Sciences and Kansino Biotech.

On April 9, the adenovirus vector vaccine of the Academy of Military Medicine of the Academy of Military Sciences began to recruit volunteers for the second phase clinical trial, and it was the world’s first new coronavirus vaccine to start the second phase clinical trial.

On April 12, the new coronavirus inactivated vaccine jointly applied by Sinopharm Wuhan Institute of Biological Products and Wuhan Institute of Virology, Chinese Academy of Sciences was approved to enter clinical trials.

On April 13, the inactivated vaccine developed by Beijing Kexing Zhongwei Biotechnology Co., Ltd. was approved. [12]

On April 14th, the State Council’s Joint Prevention and Control Mechanism Scientific Research Team stated that China’s two inactivated vaccines for the new coronavirus have obtained the combined clinical trial licenses for the first and second phases of the National Medical Products Administration, and related clinical trials have been initiated simultaneously. This is the first batch of inactivated vaccines for the new coronavirus to be approved for clinical research. The two new coronavirus inactivated vaccines were developed by Sinopharm Wuhan Institute of Biological Products and Beijing Kexing Zhongwei Biotechnology Co., Ltd. in conjunction with relevant scientific research institutions. [13]

On May 26, the international authoritative medical journal “The Lancet” published a paper introducing the positive results of the first phase clinical trial of a new coronavirus vaccine candidate developed by the Chinese team. Volunteers vaccinated with 3 different doses of candidate vaccines all produced neutralizing antibodies and T cell immune responses against the new coronavirus, and showed good tolerance; within 28 days after vaccination, most people’s neutralizing antibodies increased More than 4 times. [14]

On June 5th, the fully human monoclonal antibody developed by Gao Fu et al. entered clinical trials [15].

On June 16, the blind review and staged unblinding meeting of the Phase I/II clinical trial of the new coronavirus inactivated vaccine developed by the Wuhan Institute of Biological Products of China National Pharmaceutical Group was held simultaneously in Beijing and Henan. The Special Vaccine Class of the Joint Prevention and Control Mechanism of the State Council and relevant experts from the Biotechnology Development Center of the Ministry of Science and Technology attended. The unblinding results showed that: the safety after vaccination was good; there was no serious adverse reaction; after different procedures and different doses, the vaccinated persons in the vaccine group all produced high-titer antibodies; after two doses of 28-day program; neutralizing antibody positive conversion The rate is 100%.

On June 19, the novel coronavirus mRNA candidate vaccine (ARCoV) jointly developed by the Academy of Military Medicine of the Academy of Military Sciences and local enterprises has officially passed the clinical trial approval of the National Medical Products Administration. This is the first mRNA vaccine approved for clinical trials in China. On the same day, the National Medical Products Administration approved the COVID-19 recombinant protein vaccine jointly developed by the Institute of Microbiology of the Chinese Academy of Sciences and Anhui Zhifeilong Kema to enter clinical trials. This is after the adenovirus vector vaccine and inactivated vaccines entered clinical trials. , The COVID-19 vaccine developed by another new technical route has entered the clinical trial stage [15].

On June 28, Gao Fu and other scholars published a study online in the top international academic journal “Cell”, entitled “A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS”, providing a The universal design of β-coronavirus vaccines against COVID-19, MERS and SARS [15].

On June 29, Cansino Biological Co., Ltd. announced that the recombinant new coronavirus vaccine (adenovirus vector) was approved for military special needs.

On July 20, the Chinese research team published a paper in the British medical journal The Lancet, saying that they conducted a phase 2 clinical trial of a new coronavirus vaccine. The results showed that the vaccine is safe and can induce immunity in the human body. Answer [6].

On July 22, Zheng Zhongwei, director of the Science and Technology Development Center of the National Health Commission and the leader of the vaccine research team of the Joint Prevention and Control Mechanism of the State Council, said in the program that some countries has officially launched the emergency use of the COVID-19 vaccine. [16] The purpose of emergency use is to first establish an immune barrier among special populations such as medical personnel, epidemic prevention personnel, border inspection personnel, and personnel who guarantee basic urban operations, so that the operation of the entire city will have a stable guarantee.

On August 5, according to the latest news from Sinopharm Group, the COVID-19 inactivated vaccine production workshop of the Beijing Institute of Biological Products passed the joint biosafety inspection organized by the relevant state departments and was qualified for use. Previously, the workshop had obtained a COVID-19 vaccine production license. [17]

On August 16, according to the State Intellectual Property Office, the COVID-19 vaccine (Ad5-nCoV) patent application jointly filed by the team of Academician Chen Wei of the Academy of Military Medical Research of the Academy of Military Sciences and Cansino Bio has been granted patent rights. This is China The first COVID-19 vaccine patent. [18]

On August 19, according to the State Intellectual Property Office, after verification, the patent application for the vaccine was titled “a recombinant new coronavirus vaccine using human replication-deficient adenovirus as a vector”. The patent application number was 202010193587.8. The Academy of Military Sciences of the Chinese People’s Liberation Army Academy of Military Sciences and Kansino Biological Co., Ltd. The inventor is Chen Wei, etc., and the application date is March 18, 2020. After submitting a priority review request, the State Intellectual Property Office will After issuing a patent authorization notice, the bureau will announce the authorization of the patent after the applicant has completed the patent registration procedures in accordance with the law. [19]

On August 20 and August 21, Sinopharm Sinopharm signed cooperation agreements with Peru, Morocco and Argentina on phase III clinical trials of the COVID-19 inactivated vaccine and held the launch ceremony. This marks the overall acceleration of the Phase III clinical trials of China’s new biological COVID-19 inactivated vaccine. More sample sizes and clinical trial data in different regions will greatly enhance the marketing process of the COVID-19 inactivated vaccine. [16]

On September 25, the State Council Information Office briefed. Wu Yuanbin, director of the Department of Science and Technology for Social Development of the Ministry of Science and Technology, revealed that 11 new coronavirus vaccines in some countries are currently in clinical trials. Four vaccines entered Phase III clinical trials, of which three were inactivated vaccines and one was adenovirus vector vaccine. [20]

On September 25, the State Council Information Office held a briefing. Wu Yuanbin, director of the Department of Social Development and Science of the Ministry of Science and Technology, revealed at the meeting that 11 new coronavirus vaccines in China have entered clinical trials. Four vaccines entered Phase III clinical trials, of which three were inactivated vaccines and one was adenovirus vector vaccine. Recombinant protein vaccines, nucleic acid vaccines, and attenuated influenza virus vector vaccines are rushing to carry out phase I and phase II clinical trials. [twenty one]

On October 8, China signed an agreement with the Global Alliance for Vaccines and Immunization to formally join the “COVID-19 Pneumonia Vaccine Implementation Plan.” This is an important measure for China to uphold the concept of a community of human health and fulfill its commitment to promote vaccines as a global public product.

On October 20th, Tian Baoguo, deputy director of the Department of Social Development and Science and Technology of the Ministry of Science and Technology, said at a press conference on the Joint Prevention and Control Mechanism of the State Council that China has four new coronavirus vaccines that have entered the phase III clinical trials. [1]

Other countries

Australia

It was reported on January 22, 2020 that the University of Queensland in Australia is using a patented technology to quickly produce a vaccine against the new coronavirus. Keith Chapel of the University of Queensland, one of the leaders of the scientific research project, told Xinhua News Agency that the school’s research team has obtained the genetic sequence of the new coronavirus and is in the early stages of developing a related vaccine. This patented technology called “molecular tweezers” developed by the University of Queensland research team can increase the stability of viral proteins. The research team tried to use this technology to develop targets for Middle East respiratory syndrome coronavirus, Nipah virus, Ebola virus and The influenza virus vaccine has achieved very satisfactory experimental results. [twenty two]

United States

On February 19, 2020, Sanofi Pasteur, the global vaccine division of Sanofi, announced that it will cooperate with the US Biomedical Advanced Research and Development Agency (BARDA) to accelerate development using an advanced genetic recombination technology platform New coronavirus (COVID-19) vaccine.

On March 2, 2020, the University of California, Riverside issued a statement stating that the research team found the drug target protein in the new coronavirus and cracked the 3D structure of the protein, which will help develop the treatment of new coronavirus Drugs for pneumonia. The research team consists of researchers from the University of California, Riverside, the University of Chicago, the U.S. Department of Energy Argonne National Laboratory and Northwestern University. [twenty four]

On April 7, 2020, a US company announced that the US Food and Drug Administration (FDA) has accepted the company’s new drug clinical trial (IND) application for the new coronavirus candidate DNA vaccine INO-4800. [25]

On May 5, 2020, Pfizer of the United States has begun testing an experimental vaccine in the United States to combat the new coronavirus. [26]

Russia

On February 26, 2020, Russian Deputy Prime Minister Golikova told the media that Russian researchers have obtained the new coronavirus strain and have developed 5 prototype vaccines against the virus. The Russian “Vector” National Science Center for Virology and Biotechnology has developed five prototype vaccines against the new coronavirus, but they are still in the initial stage of vaccine development. [27]

On March 20, 2020, the Russian Federation Biomedical Agency issued an announcement stating that experts from the agency are stepping up the development of vaccines against the new coronavirus and have developed three prototype vaccines. [28]

On August 1, 2020, Russian Health Minister Murashko stated that the COVID-19 vaccine will be vaccinated for free. Murashko said: “We plan and budget to fully cover the cost of the COVID-19 vaccination. The vaccination plan is to vaccinate as planned.” Murashko also said that Russia will be vaccinated on a large scale in October, and doctors and teachers are given priority. At the same time, the government will monitor vaccinated people. [29]

On August 11, 2020, according to the Russian Satellite News Agency, the Russian Minister of Health stated that the first registered COVID-19 virus vaccine was named “Satellite-V” (SPUTNIK V), and pointed out that vaccination of the COVID-19 virus vaccine can make people develop long-term Immunity, which can last for two years, is expected to start circulation on January 1, 2021. [30]

Israel

On February 27, 2020, the Israeli Ministry of Science and Technology announced that the country’s researchers are accelerating the development of an oral novel coronavirus vaccine, which is expected to start clinical trials within 90 days. Israel’s Minister of Science and Technology Ophir Akunis said that the institution that is developing this vaccine is the Miguel Galilee Institute, and the Ministry of Science and Technology will expedite all approval processes related to this vaccine to promote the vaccine’s early launch. [31]

Korea

On March 4, 2020, the Korean Institute of Chemistry stated that the new virus fusion research team led by the institute has found neutralizing antibodies against the new coronavirus, which will help advance the process of developing a new coronavirus vaccine. [twenty four]

Germany

According to a report on March 15, 2020, CureVac, a biopharmaceutical company headquartered in Tübingen, Germany, said that using its vaccine development platform based on messenger ribonucleic acid (mRNA) technology, it is expected to develop effective candidates against the new coronavirus within a few months vaccine. During this time, the governments of the United States and Germany attached great importance to the company’s ability to rapidly develop and produce vaccines, competing for funding and secretly competing against possible future vaccine supplies. [32]

United Kingdom

On March 17, 2020, the University of Cambridge in the United Kingdom said that a team at the school is using artificial intelligence, synthetic biology and other technologies to accelerate the development of a new coronavirus vaccine. According to Professor Jonathan Heney, who led the team, the vaccine may be used in clinical trials as early as June. Prior to this, the research teams at Oxford University and Imperial College in the United Kingdom also expressed that they are working hard to develop vaccines. [33]

South Africa

On June 23, 2020, South Africa’s Golden Mountain University announced at an online press conference that South Africa will start the first clinical trial of the COVID-19 vaccine on the African continent. The vaccine used in the trial was developed by the Jenner Institute of Oxford University, and is currently undergoing clinical trials in the UK. [34]

3. R & D progress

Separation of virus species

On January 24, 2020, the National Pathogenic Microorganism Resource Bank released information on China’s first virus species successfully isolated by the Institute for Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, as well as its electron micrographs, new coronavirus nucleic acid detection primers and probes Sequence and other important authoritative information released for the first time in China, and provide shared services. [35]

Clinical Trials

China

At 20:18 on March 16, 2020, a scientific research team led by Academician Chen Wei of the Academy of Military Medicine of the Academy of Military Sciences was approved to start clinical trials. [36]

Phase I trial

There are not many volunteers needed for the Phase I trial. They are limited to permanent residents in Wuhan. Residents with registered permanent residence in Wuchang, Hongshan, and Donghu Scenic Areas are preferred, aged 18-60 years old. Volunteers will be divided into three groups, low-dose group, medium-dose group and high-dose group, with 36 people in each group. After screening and physical examination, qualified volunteers can be vaccinated. The following 14 days will be the intensive isolation observation period. [37]

On March 31, 2020, the first batch of volunteers vaccinated with recombinant new coronavirus vaccine (adenovirus vector) has reached the 14-day medical observation period. As of April 2, 108 subjects in the Phase I clinical trial of the COVID-19 vaccine in Wuhan have all completed vaccination, and 18 of them have ended their isolation. Everyone has to take a CT when they are released from isolation, and they are in good physical condition. [38]

The Phase I clinical study recruited a small number of subjects to evaluate the safety of the vaccine and whether it can produce an immune response.

Phase II trial

On April 9, 2020, the Phase II clinical study of the COVID-19 vaccine launched volunteer recruitment. The phase II clinical study selected low- and medium-dose vaccines for the trial. The study was divided into 3 groups, namely the medium-dose vaccine group (250 cases), the low-dose vaccine group (125 cases) and the placebo control group (125 cases). Both the vaccine and the placebo control were jointly developed by the Institute of Bioengineering of the Academy of Military Medicine of the Academy of Military Sciences and Kansino Biotech. According to the requirements of the research protocol, each volunteer must complete a research visit on the day of vaccination, the 14th day, the 28th day, and the 6th month. A total of four blood samples are required. The number of subjects in the phase II clinical study is moderate to adjust and improve the procedures and procedures of clinical vaccination and obtain statistical data such as adverse reactions.

On April 13, 2020, the new coronavirus vaccine entered the phase II clinical trial. The phase II clinical trial of the recombinant new coronavirus vaccine was led by the Jiangsu Provincial Center for Disease Control and completed by the Hubei Provincial Center for Disease Control and Zhongnan Hospital. In clinical trials, volunteers do not need to undergo 14-day intensive observation.

Phase III trial

Phase III clinical studies mainly evaluate the effectiveness of the vaccine and recruit larger-scale subjects to confirm that the vaccine can achieve the expected purpose of preventing infection or reducing symptoms.

On August 20, 2020, the clinical trial of China’s bio-COVID-19 inactivated vaccine under the Sinopharm Group was launched in Peru (Phase III). After obtaining the UAE clinical trial approval on June 23, it has been awarded the Phase III clinical trial approval by the National Institutes of Health of the Ministry of Health of Peru. [39]

United States

On February 24, 2020, the American biotechnology company Moderna announced that it has shipped the company’s first batch of new coronavirus vaccine mRNA-1273 to the National Institute of Allergy and Infectious Diseases for the first phase of clinical trials. test. [40]

On March 5, 2020, according to the official announcement of the American biotechnology company Moderna, the U.S. Food and Drug Administration (FDA) has completed the review of the company’s new coronavirus mRNA vaccine-“mRNA-1273” and approved its entry Clinical Trials. [41]

On March 16, 2020, the National Institutes of Health said that a new coronavirus vaccine developed in the United States began the first phase of clinical trials on the same day, and the first volunteers enrolled in the group have received experimental vaccine injections. [42]

4. Vaccine application editor

On October 8, 2020, China signed an agreement with the Global Alliance for Vaccines and Immunization to formally join the “COVID-19 Pneumonia Vaccine Implementation Plan.” This is an important measure for China to uphold the concept of a community of human health and fulfill its commitment to promote vaccines as a global public product. [43]

In October 2020, the COVID-19 vaccine will not be included in the medical insurance, but the COVID-19 pneumonia related treatment drugs will be included in the new scope of the medical insurance catalog. [44]

On the afternoon of October 15, 2020, the Center for Disease Control and Prevention of Jiaxing City, Zhejiang Province released the “Instructions for COVID-19 Vaccination” on its official WeChat. The new coronavirus vaccination is administered in 2 doses with an interval of 14-28 days. The vaccine price is 200 yuan per tube. The total dose is 400 yuan. [45]

As of October 20, 2020, China has vaccinated a total of about 60,000 subjects, and no serious adverse reactions have been reported.

5. Social influence

On April 13, 2020, an expert group composed of more than 120 scientists, doctors, funders and manufacturers around the world issued a public declaration, promising to work together to accelerate the development of the COVID-19 vaccine under the coordination of the World Health Organization.

The declaration stated that as part of international cooperation in the fight against the epidemic, these scientists, doctors, funders and manufacturers will, under the coordination of the WHO, work together to promote the accelerated “access” of the COVID-19 vaccine. Although it takes time to develop a universal vaccine, the vaccine will ultimately play an important role in controlling this global pandemic.

The declaration said that during this period, experts called for community interventions to reduce the spread of the virus and protect the people, including vulnerable groups, and promised to use the time gained by taking such measures to develop vaccines as soon as possible.

The declaration said: “We will continue to work hard to strengthen the unprecedented global collaboration, cooperation and data sharing already underway. We believe these efforts will help reduce inefficiency and duplication of labor. We will make unremitting efforts to improve the The possibility for everyone to provide one or more safe and effective vaccines.[46]

In July 2020, Academician Gao Fu, director of the Chinese Center for Disease Control and Prevention, stated that he had been injected with an experimental new coronavirus vaccine, hoping to increase public confidence through this move and vaccinate after the vaccine is approved[15].