The mRNA new crown vaccine competition is in full swing, and more than 10 domestic pharmaceutical companies are deployed!

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed 300 million people in the past two years since the World Health Organization declared a public health emergency of international concern (PHEI.

Transmissibility, fitness, infectivity and/or evasion of host immune responses,

The latest WHO-designated SARS-CoV-2 VOC Omicron (also known as.

Omicron carries an unprecedented number of mutations/deletions/insertions (over 30) in the spike (S) protein and the receptor binding domain (RBD), the primary target of host immune responses and vaccine development

From the perspective of global approved vaccines, there are mainly three categories: mRNA vaccines, inactivated vaccines and adenovirus vector vaccines

mRNA vaccines, inactivated vaccines and adenovirus vector vaccines

A total of 6 new crown vaccine products in China have obtained marketing authorization or emergency use authorization, including 4 inactivated vaccines, 1 recombinant protein vaccine, and 1 adenovirus vector vaccine, but no mRNA new crown vaccine has been approv.

A total of 6 new crown vaccine products in China have obtained marketing authorization or emergency use authorization, including 4 inactivated vaccines, 1 recombinant protein vaccine, and 1 adenovirus vector vaccine, but no mRNA new crown vaccine has been approv.

Picture from: "mRNA vaccine is expected to become the terminator of the global new crown epidemic"

Compared with other types of vaccines,

Compared with other types of vaccines,

What are the advantages of mRNA vaccines?

What are the advantages of mRNA vaccines?

mRNA vaccines are based on the characteristics of mRNA-directed protein synthes.

Compared with traditional vaccines, mRNA vaccines have many advantages, such as safe preparation, high efficiency and reliable quali.

At present, mRNA vaccines mainly face two difficulties: one is the synthesis and purification of mRNA with sufficient protein expression, and the other is the effective targeted delivery of mRNA in vi.

Advantages of mRNA vaccines

First, in terms of safety, since mRNA is non-infectious and non-integrating, there is no potential risk of infection or insertion mutation ;

No potential risk of infection or insertional mutation

Secondly, in terms of curative effect, various modifications make mRNA more stab.

Efficient in vivo delivery can be achieved

Finally, in terms of production, mRNA vaccines have the potential for rapid, economical and scalable productiondue to the high yield of in vitro transcription reactio.

Potential for fast, economical and scalable production

Despite the obvious advantages in development and production, the current commercial mRNA vaccine production technology is still in its infancy, and its maturity is still far from that of traditional vaccines, and many aspects need to be improv.

The main challenges include expensive raw materials, obvious drug side effects, dependence on the cold chain of transportation, the need for multiple injections of immunization, and the existence of safety dose bottlenecks, e.

mRNA vaccines still have potential risks

What is the effect of mRNA vaccines against new coronavirus mutant strains?

What is the effect of mRNA vaccines against new coronavirus mutant strains?

Indeed, accumulating evidence suggests that Omicron variants largely escape the effects of vaccination, convalescent sera, and most recognized monoclonal antibodi.

A report from the.

mRNA vaccines are very effective in preventing severe illness and death

At present, most of the mRNA vaccines that have been vaccinated on the market are still manufactured based on the sequences of early strai.

Three doses of mRNA vaccine prevent severe disease rate of 94%

The report published by Professor Yuan Guoyong of the University of Hong Kong in the journal "Clinical Infectious Diseases" shows that in terms of neutralizing antibodies, whether the first two doses of Kexing, Pfizer or BNT (Fubitai), if the third booster dose is inoculated with BNT, The effective rate increased to 89% 14 days after inoculati.

In contrast, if the three doses of Sinovac were given, the effectiveness was 3
However, the effectiveness of three doses of Sinovac in preventing severe illness and death is still 98%, because Sinovac vaccine can still stimulate T cell protection, so in this sense, Sinovac vaccine is not without value as a boost.

The Yale study, published in the journal Nature, found that two doses of the Sinovac vaccine against Omicron "did not produce neutralizing antibodies," but the mRNA vaccine significantly increased antibody levels

Two doses of Sinovac vaccine 'cannot produce neutralizing antibodies' against Omicron, but mRNA vaccine significantly increases antibody levels

Early research from Hong Kong showed that two doses of Sinovac vaccine require different vaccines as boosters, preferably vaccines with mRNA technology

Two doses of Kexing vaccine need to be vaccinated with different vaccines as boosters, preferably vaccines with mRNA technology

A study conducted by Oxford University and the Brazilian government found that the proportion of neutralizing antibodies in the three-dose mRNA vaccine reached 90%, but the proportion of neutralizing antibodies in the three-dose Sinovac vaccine was 35%

The proportion of neutralizing antibodies in the three-dose mRNA vaccine reached 90%, but the proportion of neutralizing antibodies in the three-dose Sinovac vaccine was 35%

According to the relevant data, the fourth dose of mRNA vaccine is immunogenic, safe, and effective to a certain extent (mainly against symptomatic diseas.

The maximum immunogenicity of the mRNA vaccine was obtained after three doses, while antibody levels recovered after the fourth do.

Not long ago, academician Zhong Nanshan announced the results of a Brazilian heterologous vaccination that also showed that the protection rate of the vaccine against infection dropped to 37% after 6 months of inoculation with two doses of inactivated vaccine, and the rate of severe disease prevention was 7
At this time, if a dose of mRNA vaccine is strengthened, the effectiveness of the vaccine against infection surges to 97% after 14 to 30 days, and the rate of severe disease prevention reaches 9

According to the Financial Times, Johns Hopkins University epidemiologist David Dowdy said the current vaccine is still very effective, but it makes sense to develop a booster shot against the Omicron vir.

" Viruses evolve, and our vaccines should evolve , " Dowdy sa.

" The beauty of a bivalent vaccine is that it keeps a product that we know works and adds a product that targets the current vir.

"

Viruses are evolving, so should our vaccines

The latest progress of mRNA vaccines at home and abroad?

The latest progress of mRNA vaccines at home and abroad?

At present, the development of global mRNA vaccines is mainly concentrated in three companies, BioNTech, CureVac AG and Moderna , which cooperate with major pharmaceutical compani.

In addition to the three mRNA giants, there are also companies such as TranslateBio and I.

, eTheRNA Immunotherapies, ethris GmbH, Argos Therapeutics, In-Cell-Art, Tiba Biotech, Arcturus Therapeutics, Arbutus Biopharma Corporation, Acuitas Therapeutics, e.

Delivery and other fields have their own expertise, and the progress is more promine.

According to the British Financial Times, the US pharmaceutical company Moderna said it is currently prioritizing the development of a new vaccine against the fast-spreading Omicron variant of the virus, which will be released in the fall

Compared with the accumulation of more than ten years in Europe and the United States, China's gap in the mRNA field is still relatively obvio.

Research on mRNA drugs in Europe and the United States has entered a stage of explosive growth, but China has just started in this field

From the perspective of technology and intellectual property rights, mRNA vaccines are gradually developing into "stuck neck" technolo.

The domestic companies that deploy mRNA technology include Fosun Pharma, Aibo Bio, Watson Bio, Livanda Bio, Si Micro, Bendao Gene, Shenxin Bio, Jiachen Xihai, Lanque Bio, Minuo Hengkang, Thick Storage Nano, Guan Hao Biology,
e.

The development of global mRNA vaccines is mainly focused on three companies, BioNTech, CureVac AG and Moder.

Moderna said that the company is currently prioritizing the development of a new vaccine against the rapidly spreading Omicron variant virus, and will release European and American countries in the fall for mRNA dru.

Research has entered a stage of explosive growth, but China has only just started in this fie.

The domestic companies that deploy mRNA technology include Fosun Pharma, Aibo Bio, Watson Bio, Livanda Bio, Sri Lanka, Bendao Gene, Shenxin Biology, Jiachen West Sea, Blue Magpie Biology, Minuo Hengkang, Thick Storage Nano, Guanhao Biology, e.

0 Watson Bio-Aibo Bio

At present, the fastest-growing mRNA new crown vaccine in China is Watson Bio-Aibo's mRNA new crown vaccine (ARCoVa.

In June 2020, ARCoVax was officially approved by the National Medical Products Administration for clinical trials, and it is the first new crown mRNA vacci.

According to Watson Bio’s announcement in March this year, the on-site work of the domestic phase III clinical trial of ARCoVaX is basically completed, and data collation and continuous serum testing are in progre.

The international multi-center phase III clinical trial has also made phased progress, and case collection is being carried o.

Continue to communicate with local drug regulatory authoriti.

At the same time, clinical trials of strengthening acupuncture are also underw.

The report showed that the ARcoVax vaccine was safe and well tolerated at all five doses, and could induce strong humoral and cellular immune respons.

It is the first new crown mRNA epidemic approved for clinical trials in China

0 Sri Lanka Microorganisms

As an early platform enterprise in China to develop mRNA drug R&D and production, Sri Lanka launched the new crown mRNA vaccine research and development project in January 2020 and completed the pharmacodynamic research of all candidate vaccin.

In January 2021, it obtained the clinical trial approval and became the The second domestic mRNA new crown vaccine that has entered the clinical stage in China

In September 2021, Sri Lanka stated that the first-generation mRNA vaccine phase I clinical trial has ended, and the second-generation new crown mRNA vaccine for the mutant strain has obtained clinical approval from Laos, and overseas clinical trials will be launched so.

Recently, the new coronavirus mRNA vaccine independently developed by Sri Lanka has been approved by the State Food and Drug Administration, and clinical trials will be carried o.

The iterative vaccine developed by Sterling Microbes was approved for clinical trials this ti.

This vaccine includes the D614G mutation of various new coronavirus variants such as Delta and Omicron in the research and development desi.

The strain has protective efficacy and has a certain broad spectr.

The second domestic mRNA new crown vaccine that has entered the clinical stage in China contains the D614G mutation of various new coronavirus variants such as Delta and Omicron

0 Emmy Vaccine

Emmy's new coronavirus mRNA vaccine LVRNA009 was approved by the State Food and Drug Administration for clinical trials in March 202 It is also the third domestically-made mRNA new crown vaccine approved for clinical trials
after Aibo and Sri Lank.

It has entered Phase II/III clinical trials and has submitted a sequential vaccination applicati.

It is understood that Amy Vaccine is currently deploying modular production workshops for mRNA vaccines in many plac.

The factory is expected to be completed by the end of this year and put into operation next year, with an estimated annual production capacity of 400 million dos.

In addition, the Emmy vaccine also has a new coronavirus delta variant mRNA vaccine under development, which is in the preclinical stage

The third domestically produced mRNA new crown vaccine Emmy vaccine approved for clinical trials There is also a new coronavirus delta variant mRNA vaccine under development, which is in the preclinical stage

0 Ribo Bio-Agna Bio

In November 2021, the new coronavirus mRNA vaccine applied by Ribo Bio and Agna Bio was approved by the State Food and Drug Administration for clinical tria.

On January 10, 2022, the Phase I clinical trial of the vaccine was officially launched in Chengdu

Phase I clinical trial of the vaccine was officially launched in Chengdu

0 CSPC Group

On April 3, CSPC announced that its new coronavirus mRNA vaccine "SYS6006" has been approved by the China National Medical Products Administration for clinical research in Chi.

At present, SYS6006 is included in the special approval process by the State Food and Drug Administration

It is understood that SYS6006 has been designed with targeted antigen mutations according to the epidemic situation of the stra.

Preclinical studies have shown that the product has good immune protection efficacy against the current mainstream mutant strains including Omicron and Delta; through humoral immunity and cellular Immunity provides immune protection to the body, and can generate memory B cells to provide long-term protecti.

The process of SYS6006 is highly controllable, with good batch-to-batch consistency, easy to achieve scale-up and industrialization, and good stability, and can be stored at 2-8 °C for a long time

At the same time, CSPC has realized internalized production and localized substitution of key production raw materials and auxiliary materials for mRNA technology, which can meet the needs of large-scale production capacity supp.

At present, SYS6006 has been included in the special approval procedure by the State Food and Drug Administration and can be stored at 2-8℃ for a long time

0 CanSino

On April 4, CanSino announced that its new coronavirus mRNA vaccine has obtained approval for drug clinical trials from the State Drug Administrati.

The results of preclinical studies have shown that the vaccine can induce high titers of neutralizing antibodies against a variety of important variants identified by the World Health Organization (including the current circulating strain) , which is comparable to the existing new crown vaccine developed based on the prototype stra.

Stronger than broad-spectrum and more effective in protecting the body from infection by existing varian.

The vaccine can induce high titers of neutralizing antibodies against a variety of important variants identified by the World Health Organization (including current circulating strains)

0 Westin Biology

Founded in July 2021, Westin Biotech has developed mRNA vaccines against new coronavirus mutant viruses such as Omicron and Delt.

The vaccine has applied to the State Drug Administration for clinical research approval of new dru.

mRNA vaccines against new coronavirus variants such as Omicron and Delta (Delta)

0 Ricogi Bio

In August 2021, Ruike Bio and Ruiji Bio established a joint venture, Ruikeji Bio, to develop and commercialize mRNA vaccin.

Ruike Bio said that it will submit an IND application for the lyophilized mRNA vaccine R520A designed against the Omicron variant to the regulatory agency in the first half of 202 On February 10, 2022, the preclinical data of Ricogi Bio’s lyophilized mRNA COVID-19 vaccine was published in the biology preprint journal BioRx.

The data show that the Delta strain lyophilized mRNA COVID-19 vaccine induces high levels of neutralizing antibodies against the prototype strain and the current major global strain Omicron in mi.

In the hACE2 transgenic mouse challenge assay, two doses of immunization 14 days apart provided complete protection against challenge with the Delta stra.

At the same time, the lyophilized mRNA COVID-19 vaccine of Ruikeji Bio is also the first mRNA vaccine in lyophilized form in the world

The vaccine adopts the LNP delivery system and applies the self-developed freeze-drying technology to achieve formulation stability at 4°C and 25.

The vaccine can be stored and transported under conventional cold chain conditions , which greatly improves accessibili.

The freeze-dried mRNA vaccine R520A designed for the Omicron variant strain The lyophilized mRNA COVID-19 vaccine of Ruikeji Bio is also the world's first mRNA vaccine vaccine in freeze-dried form, which can be stored and transported under conventional cold chain conditions

0 Sinopharm Zhongsheng Funuojian

On December 9, 2021, Sinopharm Group stated that Sinopharm Nuojian has started the research and development of Omicron strain vaccine on the basis of the research and development of "Delta+" (Delta+) variant mRNA vaccine , and plans to complete the intermediate test and research work as soon as possib.

On the basis of the development of the Delta+” (Delta+) variant mRNA vaccine, the development of the Omicron strain vaccine was launched

1 Blue Magpie Creatures

On January 28 this year, Watson Bio and Blue Magpie signed the "New Coronavirus Variant mRNA Vaccine Technology Development and Commercialization Cooperation Agreemen.

According to the agreement, Blue Magpie is mainly responsible for antigen design, mRNA sequence design and optimization, plasmid process development, delivery system screening and optimization, mRNA vaccine production process research and quality standard research for target drug development, and in vitro experiments and preliminary effica.

Preparation of mRNA vaccines for scientific evaluation and toxicological approval and clinical applicati.

On February 21, Fudan University, Watson Bio, and Lanque Bio signed a tripartite strategic cooperation agreement to jointly promote the development and commercialization of the "new coronavirus mRNA vaccine"

Fudan University, Watson Bio, and Lanque Bio signed a tripartite strategic cooperation agreement to jointly promote the development and commercialization of the "new coronavirus mRNA vaccine"

References:

References:

In the shadow of Delta, can mRNA vaccines be the antidote to the epidemic?

In the shadow of Delta, can mRNA vaccines be the antidote to the epidemic?

Dawn appears! mRNA vaccine, made in China!

Dawn appears! mRNA vaccine, made in China!

"Research on the Development Situation of mRNA Vaccines"

"Research on the Development Situation of mRNA Vaccines"

mRNA vaccine is expected to be the terminator of the global new crown epidemic

mRNA vaccine is expected to be the terminator of the global new crown epidemic

10 domestic new crown mRNA vaccines, how is the progress?

10 domestic new crown mRNA vaccines, how is the progress?

Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron

Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron

Rapid development of an updated mRNA vaccine against the SARS-CoV-2 Omicron variant

Rapid development of an updated mRNA vaccine against the SARS-CoV-2 Omicron variant

Other public information

Other public information