Industry trends seem to indicate the answer, domestic mRNA COVID-19 vaccine research and development is becoming increasingly fierce.

In the first tier, among the companies that received clinical approval early last year, the only companies already in critical phase II/ III clinical trials are Emmy Vaccine and Abbott Biology.

Those in the second echelon are CSPC Pharmaceutical, CANSINOBIO, Sri Lanka, and others who have recently obtained clinical approval.

The third echelon of Wisjin Biology and Regico Biology are still in the stage of preclinical research and need to be caught up.

When nine departments, including the State Drug Administration and the Health Commission, jointly issued the 14th five-year Plan for the development of pharmaceutical industry, they pointed out that they should closely follow the development trend of vaccine technology, support the construction of mRNA vaccines, improve the production capacity of emergency research and development of vaccines, and strengthen the guarantee level of vaccine supply chain. There is no doubt that in the current critical stage of COVID-19 epidemic prevention and control, China urgently needs the local mRNA COVID-19 vaccine.

MRNA, the killer's mace to deal with virus mutation

MRNA technology, which follows the popularity of COVID-19 's epidemic situation, is not new. In the sudden, complex and changeable epidemic situation, the industry tends to have a growing consensus: mRNA COVID-19 vaccine may be the ultimate killer mace to deal with virus mutation.

This is easy to understand when you understand the principle of mRNA technology. Traditional vaccines are like delivering a computer that can express viral proteins to the human body, while mRNA vaccines are more like giving the human body an operating system to express proteins on its own. These protein molecules are independent and do not assemble into a virus, but can trigger an immune response.

Dr. Xiong Changyun, vice president of Emmy Vaccine and head of mRNA production, who has entered the II/ III phase of the clinical trial of mRNA COVID-19 vaccine, gave an example: "what mRNA vaccine brings into the human body is construction drawings, and the human body itself is used as a factory to produce preventive or therapeutic vaccines. "

Because of this, Dr. Shen Dong, CEO of Damien creature, said that the mRNA vaccine can activate two immune channels in the body-the cellular immune system and the humoral immune system, while activating cellular immunity is a mass killer. Activated T cells can directly kill the virus. For example, the traditional humoral immunity is the lock in which the virus cannot open the door of the cell and cannot enter the cell, but cellular immunity can directly kill the enemy.

As a dark horse in nucleic acid drugs in recent years, mRNA vaccine has five core advantages, which determines its ability to respond quickly to help humans fight against constantly mutated viruses.

1. MRNA can express any kind of protein, and there are many varieties.

2. MRNA can express multiple proteins at the same time, which is cheaper than traditional protein drugs.

3. The production cycle of mRNA vaccine is very short. GMP production and quality control can be completed within 1-2 months, which can deal with large-scale sudden diseases.

4. MRNA vaccine is a platform technology with strong reusability. 5. The same production line can produce hundreds of millions of vaccine products with high safety and guaranteed quality control.

The efficacy of mRNA COVID-19 vaccine has been tested by global epidemic prevention.

The two mRNA COVID-19 vaccines that have been on the market worldwide are mRNA-1273 developed by Moderna Inc and BNT162b2 developed by Pfizer Inc / BioNTech.

Researchers from Optum Labs, a scientific health care organization, wrote in the journal Nature Communications on May 2nd that they conducted a return study of nearly 4 million individuals in the United States who received two doses of mRNA-1273 or BNT162b2 vaccine and found that the two vaccines were very effective in preventing severe diseases (hospitalization, ICU or death) within 90 days of full vaccination.

As early as May 2021, researchers in Qatar reported that after being fully vaccinated with Pfizer Inc's mRNA vaccine, the protection against infection with Beta mutants (B.1.351, South African mutants) was 75%, and almost completely prevented the occurrence of severe infections in infected people. In addition, the second-generation Indian mutant B.1.617.2 (Delta mutant), which led to the aggravation of the epidemic in the UK, had 88 per cent protection against symptomatic Delta mutant infection after full vaccination.

The latest research data from the School of Public Health of the University of Hong Kong this year show that in terms of the effective rate of various vaccination combinations in preventing infection with Omicron, the effective rate of three doses of mRNA COVID-19 vaccine is much higher than that of other vaccination combinations, more than 90%. Although it has declined after half a year, it is still about 80%.

Not long ago, Academician Zhong Nanshan announced the results of a Brazilian heterologous vaccine vaccination, which also showed that six months after two doses of inactivated vaccine, the vaccine's protection against infection was reduced to 34.7%, and the serious disease prevention rate was 72.5%. At this time, if a single dose of mRNA vaccine was strengthened, the effectiveness of the vaccine against infection soared to 92.7% after 14 to 30 days, and the rate of prevention of severe disease reached 97.3%.

China's mRNA vaccine, who will be the first to hand over the excellent answer paper?

People have high hopes for the high protection of mRNA vaccine, and many netizens said, "I want to get home-made mRNA vaccine as soon as possible." Which enterprise will be the first to hand over the excellent answer paper?

The martial arts in the world are fast but not broken. In terms of the speed of clinical trials, the fastest runners are Emmy Vaccine and Amber Bio, which are undoubtedly the most promising.

• The first echelon, stepping into critical clinical trials.

1. The mRNA COVID-19 vaccine LVRNA009 of Amy vaccine has been in the critical phase II/ III clinical trial, and the product has obvious technical advantages.

The mRNA COVID-19 vaccine LVRNA009 of Amy Vaccine has now entered a critical phase II/ III clinical trial and has submitted a sequential vaccination application.

From the existing clinical data, LVRNA009 shows obvious advantages over its peers. In the phase I clinical trial, the live virus neutralizing antibody test results of the vaccine showed good safety and immunogenicity, especially the geometric mean titer (GMT) level of the middle dose group was close to 1600. All adverse events occurred at the level 1 to 2, and there were no adverse events at or above level 3.

LVRNA009 has added a special design to stabilize the advanced structure of S protein. DNA transcription and mRNA capping are combined into one step by one-step process to produce mature mRNA with a capping rate of more than 95% and a purity of more than 99%. The packaging efficiency is more than 95%, the dispersion coefficient of nanoparticles is less than 0.1, and has high inter-batch consistency. In addition, the use of LNP delivery system can not only protect mRNA, but also promote cell uptake, reduce body escape, protect mRNA molecules from recognition by TLRs, and avoid overactivation of innate immune system.

In terms of vaccine industrialization, Amy Vaccine is laying out mRNA vaccine modular production workshops in many places, and will be able to carry out batch production of mRNA COVID-19 vaccine project in June. The plant is expected to be completed in the fourth quarter of this year, with an annual design capacity of 400 million doses.

two。 Aibo Biological mRNA COVID-19 Vaccine ARCoVProgress in aX international multicenter phase III clinical trial

COVID-19 mRNA vaccine ARCoVaX, jointly developed by the Institute of military Medicine of Arbor Biology and Academy of military Sciences and Watson Biology, is basically completed in phase III clinical field work in China, and data collation and continuous serum testing are under way. International multicenter III phase clinical trials have made phased progress.

The phase I clinical data of ARCoVaX showed that in terms of neutralizing antibody titer humoral immune responses such as RBD antibody (IgG) and neutralizing antibody increased significantly on the 7th day after the second inoculation and reached the peak in 14-28 days. The specific T cell response reached the peak 7-14 days after complete inoculation (two injections). Among them, 15 μ g induced the highest titer of neutralizing antibody, which was about twice as high as that of COVID-19 convalescent patients, while the level of neutralizing antibody in 20 μ g and 25 μ g group was similar to that in low dose group.

In terms of safety, there were no serious adverse reactions within 56 days after vaccination, and most of the adverse events were mild or moderate, of which the most common adverse reaction was fever. At the same time, the fever subsided within 2 days after vaccination in all subjects, and the incidence of adverse events caused by the first and second ARCoVaX vaccination was similar.

• The second echelon, newly obtained clinical approval
  

3. Sri Lanka microorganism

Si Microbe officially announced on April 29th that its independently developed novel coronavirus mRNA vaccine has been approved by the State Drug Administration and will carry out clinical trials. The iterative vaccine developed by Sri Lankan microorganism is approved to carry out the clinical trial, which includes the D614G mutation of Delta, O'Micron and other novel coronavirus mutants, which has protective effect on the current novel coronavirus epidemic strain and has a certain broad spectrum.

The research and development of microbial mRNA vaccine is based on its own intellectual property rights lipid polymer nano-carrier technology platform (LPP/mRNA).

In terms of industrialization, Sri Lankan microorganisms have set up modern production plants in Shanghai Zhoupu and Fengxian, and the annual output of the two plants is expected to reach 400 million doses.

4. CSPC Pharmaceutical

On April 3, CSPC Pharmaceutical announced that his novel coronavirus mRNA vaccine "SYS6006" had been approved by the State Drug Administration to carry out clinical research in China.

According to the announcement, SYS6006 has carried out targeted antigen mutation design according to the epidemic situation of the virus strain, and preclinical studies have shown that the product has a good immune protection effect against the current mainstream mutant strains, including Omicron and Delta; it provides immune protection to the body through humoral and cellular immunity, and can produce memory B cells, providing long-term protection.

5. CANSINOBIO

CANSINOBIO issued an announcement on April 4, saying that his novel coronavirus mRNA vaccine had been approved by the State Drug Administration in clinical trials.

The results of preclinical studies show that the vaccine can induce high titers of neutralizing antibodies against a variety of important variants identified by the World Health Organization (WHO), including the current epidemic strains, the announcement said. compared with the existing COVID-19 vaccine based on the prototype strain, it is more broad-spectrum and can more effectively protect the body from existing variants.

• The third echelon, strive to enter the clinic as soon as possible.

A company in the third tier of research and development progress, Wisjin Biology, which is working on mRNA COVID-19 vaccine, has applied to the State Drug Administration for clinical trials, and Reggie Biology's mRNA COVID-19 vaccine is also planning to submit an IND application. There is an urgent need to speed up the progress and enter the most exploratory clinical trial stage.

According to the evaluation of the industry, the mRNA technology platform will be born as "game changers like Apple Inc and Alphabet Inc-CL C", subverting the drug development model.

We have seen that key domestic Biotech enterprises, such as Zhifei Biology, cut into the layout of mRNA technology platform by subscribing for the equity of Zhifei Biology, Kangtai Biology and Jiachen West Sea jointly carry out mRNA rabies vaccine project, and Watson Biology diversified the field of mRNA R & D by joining hands with Eber Biology and Blue Magpie Biology.

We look forward to China's local mRNA vaccine companies, which are the first to reach the end of victory, to take responsibility for the country and come up with the ultimate weapon that can end the COVID-19 epidemic as soon as possible!