COVID-19 Vaccine: How Far From Us?
COVID-19 Vaccine: How Far From Us? On December 2, the British government stated that the Medicines and Health Products Administration (U.K. MHRA) has approved the COVID-19 vaccine candidate BNT162b2 jointly developed by Germany’s BioNTech and Pfizer in the United States for emergency use in the local area and will be promoted throughout the United Kingdom from next week. BioNTech co-founder and CEO Ugur Sahin, MD, said: “The emergency use authorization in the UK marks the first time that ordinary people other than trial volunteers have the opportunity to receive the COVID-19 vaccine.” This is also the first person approved in the field of mRNA vaccine technology. Use vaccine products.
This nucleic acid vaccine is called “Fosun New Coronavirus Vaccine” in China and is jointly developed by Fosun Pharma and BioNTech. It is understood that Fosun Pharma is currently advancing phase II clinical trials in China, which is expected to accelerate the launch of the vaccine in China. According to news, in accordance with the latest announcement No. 41 of 2020 issued by the latest national drug regulatory authority, conditional approval for listing will likely be the fastest route to registration and listing.
The same vaccine has previously applied for conditional marketing authorization to the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), and has launched rolling applications worldwide, including Australia, Canada and Japan.
However, although the United States has not yet formally approved it, the Federal Aviation Administration (FAA) has arranged a chartered flight on November 27 to “bulk transportation” of vaccines from Belgium to the United States, so that the first will begin within 24 hours after authorization. Delivery and vaccination of batches of vaccines. CNN reported that the first delivery will begin on December 15.
Since the beginning of autumn and winter, the global COVID-19 epidemic has repeated, and many European countries have again adopted measures such as “closing the city” to contain the spread of the epidemic. In the last week of November, the global weekly new cases finally dropped for the first time since September. At this time, the COVID-19 vaccine frequently exploded with “violent materials”, which not only shocked the global stock market, but also boosted confidence in this global war “epidemic”.
Among the COVID-19 vaccine candidates entering Phase III large-scale clinical trials, the final data analysis of the BNT162b2 overseas Phase 3 clinical trial jointly developed by BioNTech, Fosun Pharma and Pfizer showed that the effectiveness reached 95%; the mRNA-1273 developed by Moderna in the United States The basic effect analysis of phase 3 clinical trials showed that the effectiveness was 94.1%.
At present, the two most effective COVID-19 vaccines currently announced by “officials” are derived from the third-generation vaccine-the mRNA (messenger ribonucleic acid) vaccine in the nucleic acid vaccine. If successful, it may create a milestone in the history of human vaccines.
COVID-19 triggers a revolution in vaccine research and development
From the development of the first vaccine to prevent smallpox in 1796, to the official announcement of the eradication of smallpox by the World Health Assembly in 1980, it took 184 years for mankind. With the development of vaccine technology, the research and development cycle was gradually shortened to 7 to 12 years. Previously, the world’s shortest Ebola vaccine was also used for 5 years.
However, the COVID-19 vaccine is expected to shorten the development cycle to within one year.
In this accelerated competition for the development of new coronavirus vaccines, new and old technologies competed in the same field, and they responded quickly in the first time. Five technical routes for the development of new coronavirus vaccines (inactivated vaccines, adenovirus vector vaccines, attenuated influenza virus vector vaccines) , Recombinant protein vaccines, nucleic acid vaccines) all vaccines have entered the clinical stage. Up to now, 12 of the nearly 200 COVID-19 vaccine candidates in the world have entered phase III large-scale experiments.
The BNT162b2 jointly developed by BioNTech, Fosun Pharma and Pfizer, and the mRNA-1273 developed by Moderna are all nucleic acid vaccines based on mRNA technology, which are technically different from traditional inactivated vaccines, attenuated vaccines, and subunit vaccines. They are also called It is the third-generation vaccine, which is currently making rapid progress abroad.
Since there has not been any human-use nucleic acid vaccine approved for marketing before this time, it was developed in a “short time” under the COVID-19 epidemic. The effectiveness and safety of the vaccine have always been of concern. focus.
The performance of the two mRNA vaccines in the phase III clinical data not only exceeded the 50% standard set by the World Health Organization and the US FDA, even with reference to the 50% to 60% of influenza vaccines with decades of development history. Efficiency has also taken an important step in ensuring safety and effectiveness.
“What is the concept of 95%? In a specific group of people, if you don’t get the vaccine, 100 people will get COVID-19 pneumonia. After the vaccine, only 5 people get it, and 95 people are terrible. This is the 95% protection rate. “Fosun Pharma’s senior vice president, global R&D president and chief medical officer Dr. Hui Aimin explained.
It is worth mentioning that, compared to traditional vaccines that focus on prevention and are less suitable for non-communicable diseases such as cancer, nucleic acid vaccines have both preventive and therapeutic effects. Especially the development of mRNA technology will not only apply In response to the COVID-19 epidemic, it is also expected to treat cancer and rare diseases.
BioNTech is the first company to introduce mRNA personalized tumor vaccines into the clinic. The BNT122 for metastatic melanoma, jointly developed by it and Roche of Switzerland, has started phase II clinical trials.
The development of vaccine technology is of great significance for humans to overcome infectious diseases and major diseases. The third-generation vaccine technology represented by mRNA vaccines has emerged in the COVID-19 epidemic. As Thomas Suderhoff, the winner of the Nobel Prize in Physiology or Medicine in 2013, said, “The COVID-19 pneumonia has triggered a revolution in vaccine research and development, which has completely changed the way the biomedical industry develops vaccines.”
The “young” mRNA vaccine goes fast
Four days after successfully isolating the first strain of the new coronavirus, on January 12, China shared the genome sequence information of the new coronavirus with the World Health Organization. Three days later, Barney Graham of the National Institute of Allergy and Infectious Diseases (NIAID) calculated the best target of the vaccine-Spike Protein, and found the key “key” for the new coronavirus to invade human cells.
On March 16, the first clinical trial volunteer in the United States received the first injection of Moderna’s COVID-19 vaccine mRNA-1273 in Seattle. This is only two months after the release of the new coronavirus gene sequence.
The “sweet speed” of the response is due to the technical advantages of nucleic acid vaccines.
The operating principle of the nucleic acid vaccine is to obtain the viral gene sequence, encode the gene DNA or mRNA (messenger ribonucleic acid) that can express the viral antigen protein, and inject it into the human body. The cells in the body will synthesize the virus by themselves based on this “virus file” The antigen protein of the virus simulates virus infection, thereby inducing the body to produce antibodies.
Therefore, its advantage is that it can be “artificially synthesized” by knowing the gene sequence of the virus. During the research and development process, it does not need real virus strains, nor does it need to synthesize proteins and viruses, so it has no virus components, and the process flow is relatively simple. efficient. After the outbreak of the COVID-19 epidemic, the nucleic acid vaccine technical route has been favored by the R&D teams of top pharmaceutical companies.
However, although both are nucleic acid vaccines, in the view of Dr. Hui Aimin, mRNA has more advantages in efficacy and safety than DNA. “After DNA enters the human body, it enters the cell first, and then enters the nucleus, so it has to pass through the two lines of defense of the cell membrane and the nuclear membrane of the nucleus, and then transform into mRNA in the nucleus, then come out of the nucleus, and return to the cytoplasm of the cell. , And finally translated into antigenic protein. mRNA is simple, it passes through the cell membrane, enters the cytoplasm, and is directly translated into protein in the cytoplasm. In addition, mRNA has no potential risk of inserting into the host genome.”
Dr. Hui Aimin also stated that the mRNA vaccine has a dual mechanism of humoral immunity and T cell immunity. It is highly immunogenic and does not require adjuvants.
In 2020 when vaccine research and development becomes the main theme, “young” mRNA vaccines are going fast.
In July of this year, BioNTech and Pfizer launched a phase 2b/3 clinical trial of the COVID-19 vaccine candidate BNT162b2, collecting data from about 44,000 subjects in more than 100 clinical bases in the United States, Germany, Argentina, Brazil, South Africa, and Turkey. Information, the age covers 12 to 85 years old. The final data of its statistical phase 3 clinical trial showed that of the 170 subjects infected with the COVID-19 virus, only 8 of the vaccinated subjects were infected, and 162 received a placebo.
On November 18, BioNTech and Pfizer announced that their co-cooperative COVID-19 vaccine BNT162b2 has an effective rate of 95%, and people over 65 years of age have an effective rate of 94%. No serious safety issues have been observed. They formally reported to the US FDA on November 23 Submitted an application for its emergency use authorization (EUA) for the BNT162b2 vaccine against SARS-CoV-2.
About a week later, on November 30th, Moderna of the United States announced that it had simultaneously applied to the United States and European health regulatory agencies for the company’s COVID-19 vaccine mRNA-1273 authorization.
However, the storage and transportation of mRNA vaccines must be in an ultra-low temperature environment. Therefore, if mass production is successfully achieved in the future, transportation and storage will face some challenges. And BioNTech/Pfizer’s COVID-19 mRNA vaccine has higher requirements for the “environment” than Moderna vaccine. It is reported that the COVID-19 mRNA vaccine BNT162b2 can be stored for 6 months in an ultra-low temperature freezer at -70°C, 15 days in Pfizer’s special insulated transport box, and 5 days in a normal hospital refrigerator at 2-8°C.
Fosun Pharma has already prepared for the supply in the later stage of the deployment. In September, it signed a strategic cooperation agreement on BioNTech mRNA vaccine logistics with Sinopharm. It will build a -70℃ cold storage near a Chinese airport. After the vaccine is imported from abroad and arrives in China, It will be stored in the cold storage for the first time, and then transported by Sinopharm Cold Chain to vaccination points across the country to ensure that the vaccine is at -70°C during the entire transportation process.
This vaccine revolution requires international cooperation
Unlike the rapid pre-purchasing of vaccines in other countries, in addition to deploying five technological paths at the national level for independent research and development, companies are also strengthening domestic and foreign cooperation in order to efficiently promote the development of COVID-19 vaccines.
As a Chinese pharmaceutical company with a leading international level, Fosun Pharma quickly made decisions at the beginning of the outbreak, and through international cooperation, it deployed the COVID-19 vaccine-mRNA nucleic acid vaccine on the new technology track.
In March of this year, Fosun Pharma became a strategic partner of German BioNTech in China. The two parties will jointly develop and commercialize vaccine products against the new coronavirus based on BioNTech’s proprietary mRNA technology platform in mainland China, Hong Kong, Macao and Taiwan.
Since the cooperation between the two parties, Fosun Pharma has been deeply involved in the research and development of mRNA nucleic acid vaccines. In addition to comprehensive and in-depth discussions with partners on research and development plans and advance clinical trials in China, Fosun Pharma has also designed and completed several projects including BNT162b2 with Chinese research units. The mRNA was selected for the animal challenge test of the vaccine and shared with the partners in time.
On November 13, the COVID-19 mRNA vaccine BNT162b2 was approved for clinical trials by the State Food and Drug Administration of China. However, in view of the fact that III clinical trials require large-scale populations to conduct trial data statistics, China currently does not have III clinical conditions, and Chinese vaccine companies are also seeking international cooperation.
Dr. Hui Aimin said, “There is no way to do the third phase of the COVID-19 pneumonia vaccine in our country. The Chinese vaccine is also used for the third phase abroad, and about 6% of the subjects abroad are Asian. We are working with the country. The Center for Drug Evaluation (CDE) of the Drug Administration discussed the use of bridging trial data plus foreign phase III clinical data registration.”
On November 25, Fosun Pharma and BioNTech jointly announced that the vaccine will carry out a clinical phase II bridging trial in Taizhou and Lianshui, Jiangsu, China. It plans to recruit 960 healthy subjects aged 18 to 85 through online. To evaluate its safety and immunogenicity. This will also provide critical clinical data for the widespread promotion and use of the vaccine in other countries and regions around the world, as well as its domestic market in China.
The COVID-19 epidemic is raging around the world, and vaccine research and development staged “speed and passion”. It is a matter of hundreds of millions of lives, and requires investment in new technology funds, and even more international cooperation and win-win.
On November 23, at the opening ceremony of the 2020 World Internet Conference and Internet Development Forum in Wuzhen, Zhong Nanshan, an academician of the Chinese Academy of Engineering, emphasized in a video speech that “viruses have no borders, and epidemics have no races. Facing the common crisis of all mankind, any country There is no way to be alone. The international community needs to join hands to abandon differences and develop higher, closer and more comprehensive cooperation in the fields of vaccine research and development, 5G medical care, and data sharing.”
As a model of Sino-German cooperation to promote the transformation of global scientific research results, this COVID-19 mRNA vaccine BNT162b2 not only represents the technological innovation capability of the world’s leading mRNA therapy, but also embodies China’s technical experience and wisdom.
This year, China’s mRNA vaccine technology has also made significant breakthroughs. On June 19, the new coronavirus mRNA vaccine (ARCoV) jointly developed by the Academy of Military Sciences, Yunnan Watson Biology and Suzhou Aibo Biological Company, officially passed the clinical trial approval of the National Medical Products Administration, becoming the first clinical trial approved in China MRNA vaccine.
This time, Fosun Pharma and BioNTech launched the Phase II clinical trial of the COVID-19 mRNA vaccine in China, which will promote the clinical research of mRNA vaccine in China to a certain extent. As the technology matures and international cooperation continues to deepen, mRNA vaccine technology may be further developed and applied on a larger scale.