Global covid-19 vaccine race sprint

From the publication of novel coronavirus genome sequence for the first time to the approval of several vaccine candidates, many countries around the world have entered into clinical trials in just a few months.This can be said to be a new historical record of mankind’s fight against infectious diseases.Recently, with the deepening of clinical trials, China, the United States, the United Kingdom and other countries are beginning to approach the final sprint phase.

Titanium media editor Lin zhijia

Under the severe situation of covid-19 pandemic, countries all over the world have stepped up their efforts in vaccine research and development, and started a novel coronavirus vaccine research and development competition, which can be said to be a competition of scientific research strength or a contest of comprehensive national strength.But in the final analysis, it is still the fate of mankind, and all countries want to make joint efforts to solve this sudden disaster as soon as possible.

The world health organization (who) statistics show that currently (as of May 15) 118 worldwide for COVID registered – 19 candidate vaccine research project, including China, the United States, Canada, Britain, Germany, Singapore and other top scientific research team, from 16 countries thousands of scientists are actively involved in work around the clock, tens of billions of dollars of capital from all walks of life have been if necessary vaccine project.

According to who and the national health commission of China, according to the current globally recognized and authoritative classification method, covid-19 vaccine is divided into five design routes: nucleic acid vaccine (mRNA vaccine, DNA vaccine), recombinant genetic engineering (protein recombinant) vaccine, inactivated vaccine, attenuated influenza virus vector vaccine, and adenovirus vector vaccine.

Research institutions and researchers in various countries have made different choices according to their own circumstances, and relevant developments are constantly attracting the attention of the world.Ti media App has learned from reliable sources that the results of the 108 volunteers in the phase I clinical trial of covid-19 vaccine led by academician Chen wei have come out completely, and the data results are relatively optimistic.However, there are also reports from overseas that the initial results of the vaccine trial at Oxford University are not optimistic, which has caused controversy.In the last two days, the Moderna team in the United States has also described the vaccine as having “encouraging” results in phase I human clinical trials.

How close is the vaccine progress?What are the characteristics of each of the five categories and how to judge the reliability?, so to speak, from industry to the general public, all new crown vaccine research and development of national development, security and other issues to proceed, this period, ti media cover five monthly 】 【 the vaccine new global champions league run to hope that through the difficulty of the new champions league vaccine, vaccine clinical trials process and global influenza vaccine broad understanding and depth of analytical techniques, such as competition situation, try to finish for this will be the coronavirus vaccine knowledge popularization of global competition.

According to real-time statistics released by Johns Hopkins university in the United States, as of May 21, Beijing time, a total of more than 5 million cases of covid-19 have been confirmed globally, with a total of 328,000 deaths.Peter Piot, a prominent British virologist who experienced novel coronavirus infection, wrote: “I believe that the only strategy to get out of this [covid-19] crisis is to introduce a safe vaccine ona global scale.”

Vaccine is considered as the ultimate technological weapon against novel coronavirus pandemic.This, too, is based on science and history.Vaccines have been a milestone in the fight against infectious diseases since the beginning of human history.In a sense, it is also an important node in the ongoing struggle against diseases and natural disasters.

As a relatively new technology in the medical field, vaccines can prevent/treat infectious diseases by inducing specific, active and protective host immunity from pathogenic microorganisms (such as bacteria, viruses, etc.) and their metabolites through artificial dilution, inactivation, or genetic engineering.

British doctor Edward Jenner (known as “the father of immunology”) developed the vaccine after years of research showing that people who were infected with cowpox could gain immunity to smallpox.It is also the first modern vaccine in human history.In 1980, the world health organization declared that smallpox had been eradicated from the world, making it the first human infectious disease to become extinct.And vaccines are the most important historical achievement in the fight against infectious diseases.

That’s why when novel coronavirus is spreading around the world, countries have to fight for the initiative in vaccine development.

The difficulty of covid-19 vaccine

This novel coronavirus is spreading rapidly. Many people may have noticed the expression of “herd immunity” overseas, that is, the novel coronavirus achieves “herd immunity” by acquiring antibodies through natural infection. This expression is still controversial at present.

Although titanium such as media in February cover the complete checking will be coronavirus diffusion chain, tragedy or titanium can avoid | media cover “made clear that, in current COVID – 19 patients, is not mature in vaccines and specific cases, indeed all can only rely on their own immune ability, but most of the scientific community has been consensus, really need to be able to control will be fundamentally coronavirus spread, restore normal order, still want to rely on new crown vaccine research and development and large-scale popularization.

Some studies have found that the spike glycoproteins, which are located in the outermost layer of novel coronavirus, like a raised crown, are the culprit of human infection.The coronavirus enters from mucous membrane cells such as the nasal cavity, fuses with cell membranes in the body, and attacks the immune system.Covid-19 vaccines are made by genetic engineering using viruses that contain antigenic proteins but are not infectious as the antigens of the vaccine, or by using key genes that produce antigenic proteins that can be recognized by the immune system.

The protein makes it impossible for the virus to multiply once it gets into the cell and poses no threat to the human body.A vaccine, therefore, brings this protein into the body’s immune system, allowing it to recognize the virus and produce antibodies.It’s important to note that what we’re talking about here is the way the carrier vaccine enters the body, not all vaccines enter the body that way to fight the virus.Moreover, the presence of specific antibodies is only a necessary but not sufficient condition for a vaccine to be effective.Sometimes antibodies can also be detected in the serum.

In general, if the general public is vaccinated with covid-19 vaccine, the incidence of group infection will be significantly reduced and individuals will develop immunity.

It usually takes at least 8 years or even more than 20 years for a vaccine to be developed and marketed.The speed of development of covid-19 vaccine is unprecedented, but there is still a long way to go before the vaccine is successfully developed and officially launched.

At a regular press briefing in late march, who director-general Dr. Tedros said a covid-19 vaccine is at least 12 to 18 months away.Anthony Fauci, director of the national institute of allergy and infectious diseases, has previously said that even if initial safety trials of the covid-19 vaccine go well, it will be a year and a half before it is ready for large-scale use.

(photo: Shutterstock)

Why is it taking so long to develop a new vaccine?

It is mainly due to the difficulty in r&d design, detection effect and vaccine production.

The first is the preliminary research and development design.To develop a vaccine, institutions need to know enough about the virus to be able to target it.

The new vaccine will first require the team to isolate the virus in the lab, derive the genetic sequence, and grow the new strain.Even with new protein visualization microscopes and other advances, it can take a long time to get a strain or target gene.Then, the obtained candidate strains and target gene sequences need to be sent to the research and development institutions for approval to prepare the candidate vaccine sequences.

The second is the long process of testing vaccines.When the covid-19 vaccine (candidate) is developed in the laboratory, it still needs to go through animal tests and human clinical trials, which will take a long time.

It usually takes at least three to eight years to complete a full clinical trial, and sometimes more than 10 years.Every phase of clinical trial is set with rigorous safety monitoring and strict termination criteria, and every vaccine may be halted or even terminated during the clinical period because it fails to meet the preset purpose or expected requirements.

If all goes well, the vaccine will have to wait for further research and regulatory approval before it can be marketed.

Finally, in the real world, vaccine production is a cost-intensive and high-risk area.A good vaccine should not only be safe and efficient, but also be manufactured in a stable way, cheap and readily available, and easy to store and transport.

In 1955, Cutter incident, a serious vaccine incident, occurred in the United States. It can be said that the Cutter incident is one of the most serious pharmaceutical disasters in the history of the United States.The incident has raised global standards for vaccine manufacturing processes to a whole new level.

In April 1954, the United States virologist Jonas Salk (Jonas Salk), led by the team success inactivated polio vaccine was developed, namely the Salk vaccine, carter production laboratory in California, shortly after the mass public, found the vaccine live virus caused by defective workmanship was not completely kill (not completely inactivated), SV40 contains a small amount of infectious virus in the vaccine, resist the erosion of formalin.Eventually, 40,000 children were infected, 200 were paralyzed and 10 died.

Although the curt case did not prevent Salk from becoming the mainstream polio vaccine in the United States, subsequent lawsuits and compensation have profoundly affected the vaccine regulatory system in the United States.Regulations for the production of vaccines were quickly improved.More sensitive security tests have also been introduced and recording methods improved to prevent errors from being covered up.

To sum up, in the current whole process of vaccine production, many countries have strict relevant laws and regulations, so it is difficult to shorten the vaccine production time significantly.

The process of developing a vaccine in a laboratory (image courtesy of the university of Birmingham)

Humans do not know in advance which virus will be the culprit of the next pandemic, so much of the work done on novel coronavirus vaccines involves re-establishing the process.In other words, it is unlikely that a new infectious disease will emerge at the same time that a vaccine will be made available.

However, compared with the traditional vaccine development before, some novel coronavirus vaccines can be developed by simply knowing the nucleic acid sequence of the virus, bypassing the major bottleneck of in vitro mass culture of the virus.The speed of vaccine development and production probably speaks for itself at this point in time.

However, so far, neither the recombinant adenovirus vector vaccine led by the Chinese academy of military sciences nor the RNAnovel coronavirus vaccine developed by the United States have completed clinical trials.In other words, every route has the potential to fail.

Tsinghua university school of medicine, professor zhang in App on titanium in an interview, because the vaccine development is a scientific, exploratory strong scientific research project, so the scientists must maintain the spirit of science, and then compare and identify conditions, development feasibility and safety of the new champions league vaccine as soon as possible, this process is very important.

Five design routes and five stages of covid-19 vaccine development

Therefore, the timing of the development of an approved novel coronavirus vaccine for large-scale use depends on the degree of completion of each step in the process and the practical effect of the different design routes.

According to who, according to a report of vaccine research and development need to pass this several stages: preclinical studies, declare clinical, application for clinical test units, registered clinical trials, phase I clinical trial stage, Ⅱ clinical trials, Ⅲ listed, vaccine clinical trials and vaccine production, which can be roughly divided into five stages, 22 steps:

1. Preliminary design

2. Animal experiments

3. Phase I clinical trial to understand the preliminary safety of the vaccine.

4. Phase II clinical trial to determine the immunization procedure and dose.

5. Clinical trial phase III, a larger scale vaccination trial and evaluation of side effects, requires more than 1000 volunteers, with a minimum of 3-5 months.

At present, on the COVID – 19 vaccine research and development, the world’s top team basically has entered clinical trials Ⅰ, Ⅱ period.Among them, the Chinese, American and British teams moved faster.

1. The first stage: five routes were determined in the preliminary design

We first look at each stage of the situation, the first stage of the preliminary route design, a total of five routes determined.

In the early design phase, this process is simply to verify the immunogenicity of the strain and to prepare the vaccine through various techniques. This process takes about three weeks.The vaccine can then be sent to the appropriate laboratory for approval.

Compared with previous vaccine development, novel coronavirus vaccine can be developed by simply knowing the nucleic acid sequence of the virus, bypassing the major bottleneck of in vitro mass culture of the virus.

In terms of vaccine design, according to who and NHC, covid-19 vaccine is divided into five vaccine design routes: nucleic acid vaccine (mRNA vaccine, DNA vaccine), recombinant genetic engineering (protein recombinant) vaccine, inactivated vaccine, attenuated influenza virus vector vaccine, and adenovirus vector vaccine.

China has already supported the development of novel coronavirus vaccine in five routes, all of which are proceeding in an orderly manner.

The first is nucleic acid vaccines.

This is an advanced and fashionable vaccine development technology.Divided into mRNA (messenger RNA) vaccine and DNA (deoxyribonucleic acid) vaccine, this kind of vaccine is to encode antigen protein RNA or DNA fragments directly into human cells, after injection can make the cells produce one of the main antigen proteins of the virus, so as to stimulate the immune response.Among them, novel coronavirus vaccine mrna-1273, the first one to enter clinical trial in the United States, is an mRNA (messenger RNA) vaccine, which is a kind of nucleic acid vaccine.Ino-4800, the latest vaccine to enter clinical trials, is a DNA vaccine.Therefore, the titanium media App clearly distinguishes mRNA vaccine from DNA vaccine in the classification table below (figure 1).

The second is a recombinant genetically engineered vaccine, also known as a recombinant protein vaccine.

This is a vaccine prepared after purification by expressing part of the functional genes of novel coronavirus in large quantities in cells or microorganisms.We are familiar with hepatitis b, HPV vaccine, is the use of recombinant protein technology to develop and successfully marketed.

Recombinant protein vaccine USES genetic engineering recombination technology to express the immunogenicity protein in the virus shell through bacteria or yeast, and induce the immune response of the body.

This route attracted the most team choices for its suitability for mass production.According to incomplete statistics of titanium media, recombinant protein is the most commonly used vaccine type in the new crown vaccine candidates.

The recombinant protein vaccine being developed by GSK in conjunction with the university of Queensland, for example, USES “molecular clamp” technology to bind viral proteins to form chimeric peptides that can be purified and used for rapid vaccine preparation.This technology has been used in the pre-clinical stage of influenza, MERS and other viruses vaccine, is currently used in the development of novel coronavirus vaccine.The two recombinant protein vaccines developed by the team of the shenzhen institute of immunogene therapy are now in the stage of clinical animal trials, and phase I/II human clinical trials are expected to be completed by the end of may.

The third and fourth are attenuated influenza virus vector vaccines (live attenuated influenza vaccine) and inactivated vaccines.

This is the most traditional route of vaccine research and development, with a long history of application and a large number of mature products, we are familiar with polio, hepatitis a, rabies vaccine, etc. fall into this category.The technology pathway of the novel coronavirus vaccine project has at least nine in the works.

Since these two vaccine technologies are strains with stable genetic information and antigenicity that can be guaranteed through successive generations, the development cycle is long, the rhythm is slow, and the quantity is small. Therefore, the titanium media App summarizes the two vaccines according to the classification method of who in the chart.

The fifth is a viral vector vaccine.

Its principle is to use the scientists can control the live virus (such as adenovirus) as the carrier, the target pathogens (such as will be coronavirus) of the protective antigen gene inserted into the carriers of the virus genome, and efficiently express antigen protein, the harm of high purity low risk carrier of the virus was injected into the body, induce antibody generation, thus human exposure will be coronavirus won’t cause serious diseases.

The technical path takes a long time and requires high technical requirements for carrier selection, operation and production.Although the concept has been around for more than 30 years, it is a new and popular hot technology, and its reliability has been proven by successful market launches.According to statistics from titanium media App, at least 16 covid-19 vaccines are currently being developed using this technology.

Among them, the most concerned is the team led by academician Chen wei, which developed novel coronavirus vaccine at a rapid speed, becoming one of the world’s fastest vaccines entering into clinical trials.A number of domestic research institutions, including zhejiang pukang biology, the third military medical university and xiamen university, have also announced that they will carry out clinical trials in the near future.Britain’s Oxford University and Johnson & Johnson, an American drug giant, also plan to launch clinical trials of their virus-carrying vaccines this year.

On the whole, the technical route is normal and error-free, with most clinical trials starting gradually and individual teams progressing faster.

2. The second stage: the first results of animal experiments have been obtained

In April this year, the results of the world’s first animal experimental study on covid-19 vaccine were released from the Chinese academy of medical sciences.

In the second phase of vaccine development, animal testing, the vaccine is tested on laboratory mice or primates after 63 days of development and approval.

Wang junzhi, an academician of the Chinese academy of engineering, said in late march that vaccines in China’s five major technical directions are progressing smoothly, and most of the first nine tasks identified have been completed in animal research.Most research and development teams will be able to complete preclinical studies by April and start clinical trials gradually.

On April 12, the qinchuan team of the Chinese academy of medical sciences led the uploading of animal test data of PiCoVacc (kerraf), a new coronavirus inactivated vaccine being developed by kexing middle school biotechnology co., ltd. on bioRxiv, a preprint paper platform.The results showed that the vaccine induced specific neutralizing antibodies in mice, rats, and non-human primates (rhesus monkeys) that effectively neutralized 10 representative novel coronavirus strains.Studies have shown that China’s vaccines are safe in terms of animal testing.The paper was published in the top scientific journal Science on May 6.

3, the third and fourth phases: human clinical trials I – Ⅱ period, the leading of China and the United States

The third step is already the most critical one — human clinical trial. Currently, some research teams from China, the United States and the United Kingdom have entered this stage.

Currently, clinical trials (safety tests) of covid-19 vaccine in humans are mainly divided into three phases:

Among them, the phase I clinical trial focuses on the safety of vaccine use, which is mainly determined by a small number of susceptible healthy volunteers as subjects, and the safety of vaccine is understood by the human body’s tolerance to different doses of vaccine.After a few weeks, if there are no major safety issues with the vaccine, the sample size and target population can be expanded for phase II clinical trials.The phase II trial was designed to combine the initial efficacy and safety of the vaccine in a population and to determine an immunization procedure and dose.

In clinical trials, the vaccine follows the following steps: inoculating 1 dose – producing antibodies – taking blood tests – inoculating 2 doses – increasing antibody levels – taking blood tests – blinding.

Usually, from the dose point of view, will first hit the low dose, determine the safety and then hit the high dose.Even if it’s phase I, you have to do that.From the perspective of age group, the adult group should be inoculated first, then the elderly group, then the adolescent, children and even the infant group (different vaccines target different age groups, and the target population that needs to be studied should be selected later according to specific conditions).

Since phase I and II testers are recruited from healthy individuals, only the safety of the vaccine can be determined, while the efficacy of the most popular vaccine needs to be confirmed by phase III human clinical trials.This process requires patient information with a larger sample size, and the protection rate of susceptible populations can only be determined if an epidemic cycle is observed in general infectious diseases.According to the national health commission, the trial involved thousands, if not tens of thousands, of people.

If all phase III clinical trials are successful, who approval and scientific evidence are needed before they can be approved.

In fact, because the process is so long, it is likely that an effective vaccine will not be released until after the outbreak is over.But with the covid-19 pandemic around the world, people don’t want to wait too long, and even U.S. President Donald Trump has personally pressed for time for the development of a vaccine, hoping it can be completed and put into production as soon as possible.

As of May 15, according to who statistics, there are eight candidate vaccines in the clinical stage in the world, among which four are from China, three from the United States (including Germany) and one from the United Kingdom.

Among them, three vaccines have entered phase II clinical stage in China, namely, the adenovirus vector vaccine of Chen wei’s team, an academician of the Chinese academy of engineering, which has completed the inoculation of subjects in phase I clinical trial, and is undergoing phase II clinical study, which is expected to be blinded in May.The inactivated vaccine jointly applied by wuhan institute of biological products and wuhan institute of virology, Chinese academy of sciences, has entered phase II clinical study.The inactivated vaccine, phase I/II combined clinical study developed by Beijing kexing zhongwei biological technology co., ltd. was launched in suining county, xuzhou city, jiangsu province on April 16 and is currently undergoing trials.

On April 28, the new coronavirus inactivated vaccine developed by sinopharmaceutical group China bio-beijing institute of biological products was approved for clinical trial by the state food and drug administration.

On May 15, zeng yixin, deputy director of the national health commission, said that in addition to the four who vaccines, another inactivated vaccine from the institute of medical sciences of the Chinese academy of medical sciences (the kunming institute of medical sciences) had been approved by the state food and drug administration.However, since the who filing information of the vaccine was not found in the titanium media App, there is no more public information about the inactivated vaccine, so the vaccine was not counted in this paper.According to zeng yixin, a total of 2,575 volunteers have participated in clinical trials of five vaccine projects, and no “major adverse reactions” have been reported so far. If all goes well, phase ii clinical trials of these projects will be completed in July this year.

Gao fu, director of the China center for disease control and prevention, told CGTN that China is at the forefront of covid-19 vaccine research and development, and that a covid-19 vaccine may be approved for emergency use in September, and that vaccines for healthy people will be available by early next year.

And America into human clinical trials of three vaccine, respectively is: the national institute of allergy and infectious diseases (NIAID) and Dana (Moderna) mRNA – 1273, INOVIO (INO d the pharma company) INO – 4800, the American pharmaceutical giant Pfizer (Pfizer) and Germany biotechnology company BioNTech cooperation r&d mRNA vaccine (BNT162), has approved the first two phase of clinical trial in Germany.

It is worth mentioning that mRNAnovel coronavirus vaccine mRNAnovel coronavirus vaccine 1273, developed by NIAID and mordener, skipped the animal trial and started phase I human clinical trial on March 16.According to hongtao zhang, a professor at the university of Pennsylvania school of medicine, they used data from previous animal trials of the vaccine, which followed the same route, to support safety.

Such a venture could significantly shorten the research and development period, but its effectiveness remains to be seen.

Zhang told ti media App that despite mordener’s use of this particular policy and implementation method, the safety and immunogenicity of the covid-19 vaccine will ultimately have to be evaluated in humans, which is important.

On the evening of May 18, modena released data showing that the vaccine was safe and well tolerated, producing an immune response, with the only adverse effect being redness and soreness in the arm of one of the volunteers who received the vaccine.

A large-scale clinical trial of the vaccine, known as phase III, is expected to begin in July, according to modena CEO Stephane Bancel.Mass production of the vaccine could begin as early as the fall, with annual production expected to reach 1 billion doses in the future.

The second vaccine to enter human clinical trials in the United States is ino-4800, a coronavirus vaccine based on the DNA (deoxy ribonucleic acid) drug platform developed by biopharmaceutical company Inovio in its laboratory in San Diego.INOVIO announced on April 29 that the company’s covid-19 DNA vaccine ino-4800 has completed enrollment, with a total of 40 healthy volunteers receiving the first dose of the vaccine.Results of a mid-term immune response and safety assessment are expected by the end of June.

Notably, according to the New York times, the technology used by the two companies in the covid-19 vaccine has never before produced a vaccine approved for clinical use, let alone industrial production.

In addition to modena and INOVIO, Pfizer and BioTech, a German BioTech company, jointly announced on May 5 that Pfizer’s BNT162novel coronavirus vaccine project has begun phase I/II human clinical trials.The first participants were injected in the us and the first trials in Germany were completed last week.The first participants were injected in the us and the first trials in Germany were completed last week.The companies also said that if the trials prove safe and effective, the vaccine could be produced in the United States by the end of the year, with production capacity reaching hundreds of millions of doses by next year.This means BNT162 could be one of the first novel coronavirus vaccines in the United States.

It is worth mentioning that China’s fosun pharmaceutical has signed a licensing agreement with BioNTech, which authorizes its holding subsidiary, fosun pharmaceutical industry, to exclusively develop and commercialize covid-19 vaccine products based on its proprietary mRNA technology platform in the region.However, fosun has not yet conducted clinical trials in China. As for when to start clinical trials in China, fosun said in an interview at the end of April, “as a partner of BioNTech in China, we hope to speed up clinical trials of the vaccine in China in the future.”

Trump, according to the web at a White House news conference on May 15, announced a public-private partnership designed to Speed up vaccine development, called “Warp Speed Operation (Operation Warp Speed)”, to shorten the routine of vaccine research and development time, the target system developed by the end of this year, hundreds of millions of doses of a new crown vaccine available to americans.The possibility of making novel coronavirus vaccines available free of charge is being considered.

One vaccine is in clinical trials in the UK.Called Vacuna ChAdOx1 (recently renamed AZD1222) — a joint project between Oxford University’s Jenner Institute and AstraZeneca that started clinical trials on April 23 — the university has now announced that it expects to be ready by the end of September, but will not say much more about the process in between.

John bell, dean of Oxford University’s medical school, says there are good expectations that a covid-19 vaccine will be developed within a year.

There is no evidence that has the country entered the stage 5, namely Ⅲ human clinical trials.

It is worth noting that there is a certain probability of failure in vaccine development, mainly because large-scale phase III clinical trials cannot continue due to the cut-off of the epidemic.In the case of SARS, since the epidemic was over, many SARS vaccine studies were abandoned in clinical trials, and no one developed a SARS vaccine at last.As a result, the current list of vaccine candidates may not be the last.

In an interview with ti media App, zhang said that as the global covid-19 outbreak remains stable, it may be difficult to find volunteers qualified for phase III trials.Therefore, in the final phase of large-scale clinical trials, researchers may need two ways to deal with it: one way is to do phase iii clinical work abroad, perhaps by a company or a researcher already abroad.Another option is to do it on the spot. You can take some alternative indicators. For example, this vaccine can induce good protective antibodies in the body, and it can be conditionally approved for marketing based on the alternative indicators.But you have to talk to the regulators.

Clinical Ⅲ period of uncertainty, and at present, the most optimistic theory is “individual vaccines to gain an emergency use authorization” in September, but the rhetoric is mostly in the European and American manufacturers, there is no official team ventured to guarantee vaccine available time to do.

“The key factors in vaccine development depend on science, mass production techniques, regulation and risk-benefit ratios,” said shan-yue lu, a tenured professor at the Massachusetts state university school of medicine and former President of the international vaccine society.

Lu shan believes that while insisting on vaccine research and development, the hope of controlling the covid-19 outbreak should not be placed on the vaccine, because continuous clinical verification is needed and there is not enough time. The most important means of containing the covid-19 outbreak should still rely on the public health system, the medical system and quarantine measures.

Progress of vaccine research and development and details of manufacturers in each country

For the duration of the trial, there were only a handful of flu vaccine manufacturers.

According to the global vaccine market data in 2018 released by ping an securities research institute, the four giants GSK (15%), Pfizer (13%), sanofi-pasteur (12%) and Merck (14%) occupy more than half of the global vaccine market, and their positions are difficult to be challenged.The TOP5 vaccine series accounted for nearly 30% of the global vaccine market share, and the TOP10 vaccine series accounted for 39% of the global vaccine market share.In addition, there are some manufacturers in Japan, China and Russia, whose products are sold only to their own countries.

Photo source @ping an securities research institute

However, after the outbreak of covid-19, the world turned its attention to the pharmaceutical field, and the government began to focus on and lead the vaccine research and development and investment, so these pharmaceutical companies would not miss this good opportunity to declare vaccine production.

According to incomplete statistics from titanium media App, currently there are 118 covid-19 vaccine candidate projects registered on the who official website, and 8 vaccines have entered human clinical trials. Some projects cannot be fully confirmed due to the lack of public or exclusive information sources to determine their development status.But a number of vaccine companies have said they will begin human trials by 2020.

Florian Krammer, a virologist at the icahn school of medicine at mount sinai in New York, predicts that at least 20 more vaccine candidates will enter clinical trials in the coming weeks.

In this regard, the editor of titanium media App made a table with details such as the types, r&d progress, relevant research institutions or companies of hundreds of vaccine candidates for the new crown, so as to make it easy for all users to understand and get a more intuitive view of the global vaccine competition situation:

As can be seen from the picture above of the titanium media App, the world’s major vaccine manufacturers have involved dozens of enterprises and university research institutions, covering all five covid-19 vaccine design routes.

Nucleic acid vaccine racetrack manufacturer

American unicorn Moderna

Modena is a biotechnology company based in Cambridge, Massachusetts, Boston, specializing in mRNA drug research and development, and is known for developing personalized cancer vaccines.During the zika outbreak in 2015, the company worked with NIH scientists, funded by CEPI, to develop an rna-based vaccine to protect more people from infection.

The company has produced its first candidate vaccine mrna-1273 and sent it to the NIAID vaccine research center for clinical trials, the Wall Street journal reported for the first time on February 25.Like many other novel coronavirus vaccines under development, it is designed to train the immune system to produce antibodies that recognize and block the spike proteins the virus USES to enter human cells.

Unlike other vaccine therapies in clinical trials, the coronavirus vaccine developed by modena can be used as a preventative treatment.This is good news for people in high-risk areas.

BioNTech, a German company, joined fosun to join the covid-19 circuit

On March 17, BioNTech, a German biotechnology group, announced a $135m partnership with China’s Fosun Pharma to develop a covid-19 vaccine.The company said the new vaccine would be called BNT162 and, as noted above, on May 5, it announced that the BNT162novel coronavirus vaccine project had begun phase I/II human clinical trials.

Fosun will make a $50m equity investment in BioNTech and pay the mainz-based company a further $85m for vaccine development and commercialization.

If BioNTech’s initial tests confirm that the vaccine is safe and can trigger an immune response, the company will conduct a broader clinical trial with China’s fosun, as well as partners in Europe and the us.In addition, BioNTech is working on coronavirus research with U.S. pharmaceutical company Pfizer, which has partnered with the company to develop a flu vaccine.

Inovio, an alternative company that develops DNA vaccines

Inovio, a biopharmaceutical company based in Pennsylvania, USES a slightly different technology for the covid-19 vaccine than its rivals, using DNA instead of mRNA to make the candidate vaccine.

In the wake of the covid-19 outbreak, Dr. J. Joseph Kim, chief executive officer of Inovio, said at a meeting of the coronavirus task force at the White House that the company had designed ino-4800 vaccine against novel coronavirus within three hours of the release of the virus’s genetic sequence.

In addition, he announced that his company has entered into a partnership with Beijing’s Advaccine biotechnology company, which plans to conduct a parallel phase I clinical trial in China.

DNA vaccines are more concerned with safety than mRNA vaccines.Because it does not require the management of live viruses, it may be safer and faster to develop than traditional vaccines.

So far, Inovio has produced 3,000 doses of the vaccine for human clinical trials in patients in the United States, China and South Korea.

German biopharmaceutical company CureVac

A competitor, CureVac, a german-based biopharmaceutical company, announced that it had created an mRNA vaccine in its laboratory and received funding from CEPI, the alliance for epidemic preparedness innovation founded by the bill and Melinda gates foundation, to use it in novel coronavirus vaccine technology.Officials say the company hopes to begin human clinical trials within months.

It had been reported that the us was trying to move CureVac’s research across the Atlantic, but in the end the eu wanted to bet again on keeping vaccine development in Europe.

Applied DNA Sciences/Takis Biotech

The us-based biopharmaceutical company, Applied DNA Sciences, announced in March that it had teamed up with Italy’s Takis Biotech to provide a DNA vaccine candidate for covid-19.The two companies plan to offer animal testing versions by the end of the month.

Zydus Cadlia

Zydus Cadila, an india-based drug company, announced in February that it had started two ways to develop a novel coronavirus vaccine.The first is to use a DNA ring vaccine designed to produce coronavirus proteins once in the body.The second involves genetically modified recombinant measles virus that induces novel coronavirus in the patient to produce specific antibodies.

Racetrack manufacturer of protein recombinant covid-19 vaccine

Glaxosmithkline (GSK)

British drugmaker glaxosmithkline (GSK), one of the world’s largest vaccine manufacturers, has announced a partnership with China’s four leaf clover to develop a vaccine in response to the covid-19 outbreak.It is reported that China clover biopharmaceutical is a global clinical trial phase of the biopharmaceutical company.

Using glaxosmithkline’s pandemic vaccine adjuvant platform technology, the two companies will work together to evaluate four-leaf clover protein-based coronavirus vaccine candidates (covid-19 s-trimer), according to officials.


Unlike its rivals, the maryland-based company is developing a vaccine that is sprayed into patients’ noses, rather than into their arms, as a nasal spray for flu.

The company announced in February that it had completed design and prototype studies for a novel coronavirus vaccine, and is now moving forward with animal and human trials.

Generex biotechnology

Four Chinese companies have signed contracts with Florida’s Generex to develop vaccines using the company’s proprietary immune-activation technology.Company representatives say it could be ready for human trials as early as June.

Oxford University/Advent Srl

Researchers from the university of Oxford have been working ona vaccine against MERS. When the novel coronavirus outbreak broke out, they quickly customized a new vaccine for novel coronavirus.Sarah Gilbert, professor of vaccine science at Oxford University, told The Times on Saturday that she was 80 per cent confident that her team’s covid-19 vaccine would work and that it could be ready by the end of September.Previously, it was widely believed that vaccines usually take years to develop, and the development time of covid-19 vaccine could be 12 to 18 months at the earliest.And Gilbert says human trials of the team’s vaccine will begin in the next two weeks.

Track manufacturer of adenovirus vector vaccine

CanSino Biologics

In fact, adenovirus vector vaccine is a vaccine made from recombinant adenovirus that can express protective antigen genes by recombining protective antigen genes into adenovirus vaccine genes using adenovirus as the carrier.

The 11-year-old biopharmeutical company consinobiotics announced that it is producing a new coronavirus drug candidate, known as ad5-ncov, and that the institute of bioengineering at the academy of military medicine is part of consinobiotics’ joint research team to develop the vaccine.

The novel novel coronavirus vaccine they developed together has received regulatory approval and is now ready for human clinical trials after defense and animal testing.The new phase 1 clinical trial will be conducted among healthy adults aged 18 to 60 in wuhan, China, which is the first covid-19 vaccine to enter clinical trials in China.According to information released by China’s clinical trial registry, the researchers plan to divide 108 participants into three groups to receive different doses of the vaccine.

Pre-clinical results suggest that the vaccine can induce a strong immune response in animal models and is safe, consinore said.

Vaccine manufacturers based on viral vectors


Sanofi, which is one of the world’s top vaccine companies, has been working with BARDA since 2004 to respond to pandemics, including the fight against SARS.

The company has developed a novel coronavirus vaccine, which involves exchanging a portion of coronavirus RNA with genetic material from harmless viruses.Sanofi hopes the candidate vaccine can be tested on animals within six months.Human trials could begin sometime in 2021.

Johnson & Johnson

Johnson & Johnson is working with BARDA to develop a vaccine against covid-19 using a vaccine against ebola.With funding from government agencies, the company’s plan is to inactivate the virus and produce a vaccine that triggers an immune response without causing infection.The company has not released any information about the development timeline.

GeoVax lab, United States, and wuhan enterprise BravoVax jointly fight the epidemic

Atlanta-based GeoVax announced that it had signed a letter of intent to begin developing a vaccine with wuhan-based drug maker BravoVax.According to the letter of intent, BraVax, upon receipt of GeoVax’s candidate vaccine, will be responsible for the testing and production of the vaccine, while working directly with Chinese public health and regulatory authorities.

Notably, the viral basis of GeoVax’s vaccine vector (MVA) has maintained a safety record for more than 50 years.The company is currently focusing on preventive vaccines for HIV, zika, haemorrhagic fever and malaria, as well as therapeutic vaccines for chronic hepatitis b infections and various cancers.

A company trying to weaken a living novel coronavirus: Codagenix

Codagenix, a biotechnology company based in New York, is working with the serum institute of India to develop a live attenuated vaccine against novel coronavirus.Instead of using blunt forces like heat or chemicals to kill the virus, Codagenix USES a “de-optimization” strategy to manipulate the virus to replicate but not cause disease.

The serum research institute of India says the research will enable it to expand in India.Codagenix hopes to have a candidate vaccine ready for animal trials this spring and human trials this summer.

To sum up, with several candidate vaccines entering clinical trials, China and the United States are considered to be competitive participants in the global vaccine race.

Dong Chen, dean of the tsinghua university school of medicine and an academician of the Chinese academy of sciences, told the media: “China and the United States should be the most promising countries.This is the time when China and the United States should shoulder a responsibility to world civilization.”

Dong explained that, on the one hand, the United States has strong overall medical resources and research and development capabilities.Now China is slowly making efforts, but it still lags behind the United States.In addition, fewer doctors actually do scientific research in China.In the United States, there are a large number of doctors and scientists in hospitals who are doing scientific research while seeing doctors, while in China, doctors spend most of their time seeing doctors, so the platform and conditions for scientific research are somewhat inadequate.

But dong also stressed that these problems are likely to be solved in the future as China’s economy continues to develop and its medical skills improve.

In fact, Chinese scientists have entered into clinical trials around the world in just a few months, from the first release of the novel coronavirus genome sequence to the approval of several vaccine candidates. China has set a new record in the history of fighting infectious diseases.

In the battle against the virus, researchers around the world are working together to build powerful weapons for the human campaign.

Dong Chen said, “we set aside the boundaries of countries and nations, and truly took novel coronavirus as a problem facing all mankind. We carried out good communication and cooperation, and Shared and got through technology.”We are now addressing many of the deglobalization issues that we face in the aftermath of the outbreak, and vaccine technology is a possible direction to try.”

But when it comes to vaccine development, the word “race” may convey a sense of urgency in the fight against the virus, rather than a determination to “join hands” in the fight against the epidemic.As Margaret Harris, a spokeswoman for the world health organization, said: ‘we are not in competition at the moment. We are working together to defeat a virus that is so harmful to human health.’Now we see that we all share ideas, ideas, and information, and that can really help us overcome novel coronavirus.

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