China's first mRNA vaccine was approved in Indonesia, and nearshore protein will explain the vaccine for you

mRNA therapy is being actively deployed by companies in infectious diseases, tumors, rare diseases, autoimmune diseases and other fields, and is reshaping the biomedical landscape
.

On September 30, 2022, Penny Lujito, director of Indonesia's National Food and Drug Administration, announced that the new crown mRNA vaccine ARCoV, jointly developed by the Military Medical Research Institute of the Academy of Military Sciences of the Chinese People's Liberation Army, Abogen Biosciences and Watson Biologics, has been granted emergency use authorization by the Indonesian National Food and Drug Administration for the prevention of new crown pneumonia
through active immunization in people aged 18 and above.

Photo by Sun Lei of Xinhua News Agency

ARCoV has since become the third mRNA vaccine to be marketed in the world, and Indonesia is about to achieve the first mRNA vaccine
to be produced locally.
The success of ARCoV, to a certain extent, marks that China's mRNA vaccine technology has broken the European and American technology monopoly
.

What is mRNA vaccine technology? How important is it? Nearshore proteins are here to take a closer look at it
.

History of vaccines

Summarizing the history of vaccine development, it is found that vaccine research has gone through three important stages:

The first vaccine revolution occurred in the late 19th and early 20th centuries, and attenuated or inactivated vaccines
were obtained mainly through biological passage or physicochemical treatment of pathogens.
In addition, toxoid vaccines
emerged during this period.

In the 80s of the 20th century, the advent of the hepatitis B vaccine prepared from yeast marked the arrival
of the second vaccine revolution.
There are mainly genetically engineered sub-vaccines, genetically engineered vector vaccines with dual immunity, live vaccines with gene deletions that replace or detoxify toxins, and peptide vaccines
.

In the 90s of the 20th century, mRNA vaccines that used nucleic acid DNA or RNA as vaccines were directly injected into muscles, produced corresponding antigens through expression in muscle cells, and induced immune responses from host cells marked the arrival
of the third vaccine revolution.
In 1987, Robert Malone mixed mRNA with lipid droplets and then incubated with human cell lines and found that these cells could express proteins
encoded by mRNA.
Then, after more than 30 years of efforts by hundreds of researchers, the global coronavirus pandemic that broke out at the end of 2019 gave birth to the new crown mRNA vaccine
that has been administered billions of doses around the world.

mRNA vaccine advantages

Unlike traditional vaccine manufacturing techniques, which require culturing cells or viruses, mRNA vaccine production relies on in vitro synthesis techniques, as shown in Figure 1, from in vitro transcription of mRNA to the preparation of mRNA-LNP complexes, the entire production cycle of mRNA vaccines may take only 10 days
.
When the virus mutates, mRNA vaccines can also respond
quickly by changing the genetic sequence.

The production process of mRNA vaccines

Compared with traditional vaccines, mRNA vaccines have the advantages of fast research and development, simple preparation steps, platformization, easy expansion of production capacity, and can be used for precision and personalized treatment
.
Compared with DNA vaccines, it has a fast onset, no risk of integrating the host genome, and will automatically degrade in the body, which is safer
than DNA.

In the battle against new crown pneumonia, the two mRNA vaccines from Moderna and BioNTech fully confirmed the powerful advantages
of this technology.
Clinical results have shown that BioNTech's BNT162b2 is 94% effective as a two-dose regimen, while its booster dose can increase neutralizing effect
on the Omicron variant.
The clinical phase III results of mRNA-1273 developed by Moderna showed a vaccine protection rate of 94.
1%.

Efficacy against α and β variants was 100% and 96.
4%, respectively, and slightly lower (73.
1%)
against Delta.
Its booster provides high and durable protection against the Delta variant (95.
2%), but low protection against Omicron (62.
5%)
.
Overall, although the effectiveness of the vaccine against SARS-CoV-2 decreased over time, vaccination with BNT162b2 and mRNA-1273 was still effective in preventing infection with other variants, reducing severe disease and mortality
.

The data is from the official website of the Hong Kong government

Nearshore protein mRNA raw materials and CRO solutions

Suzhou Nearshore Protein Technology Co.
, Ltd.
(hereinafter referred to as Nearshore Protein) has been deploying in the field of mRNA raw materials for many years, promoting the application of mRNA in tumor vaccines for a number of domestic oncology vaccine R&D enterprises, and becoming the main raw material enzyme supplier
of domestic infectious disease mRNA vaccines in 2020.
According to statistics, billions of doses of new crown mRNA vaccines have been administered worldwide, which has caused a huge impact
on the entire industrial chain.
In the face of the explosive growth of raw material demand, nearshore protein layout has built a GMP-grade raw material enzyme production base
.
The design scale of the base has reached an annual output of 5 billion mRNA vaccine raw material enzymes, and the first phase of construction has completed two large-scale production lines of fermentation, purification and preparation of 2000L scale, and the single-batch production scale of some varieties has reached the kilogram level
.
In the planning and design process, considering cost, long-term supply and procurement runs, nearshore protein has made 3 to 5 times redundant production capacity to ensure the continuous output
of raw materials in the next 10 years.
In addition to capacity, another dimension of supply chain issues is quality
.
mRNA vaccine belongs to a new production and quality control system, nearshore protein at the beginning of raw material production to improve quality control to the pharmaceutical level, established a strict quality management system, and passed ISO9001, 14001, 45001 and other quality management system certification, the formation of thousands of pages of technical documents, testing and management documents, and raw materials handed over to customers, in order to save customers in raw material release and other testing methods research and development costs, better focus on core research and development
.

In the golden age of global mRNA vaccine drug development, domestic mRNA vaccines will inevitably face the requirements
of policies and regulations in various regions to go overseas.
Faced with this problem, nearshore protein took the lead in considering the need for enzyme raw materials to make corresponding preparations, and in 2021, a full set of enzyme products were filed with the U.
S.
FDA DMF, so that drug declarants can directly use the DMF filing number to replace the specific information about raw materials that need to be provided during the declaration process, saving approval costs and improving approval efficiency
。 At the same time, in the face of some areas with the needs of Muslim populations, mRNA vaccine manufacturers need to ensure that all materials of their products can be traced to meet halal requirements, and it is reported that Nearshore Protein will carry out halal certification at its mRNA raw material production base Heze factory in 2022, eliminating the worries
of mRNA vaccine manufacturers.

In addition to raw material supply, nearshore protein is also developing mRNA stock solution preparation and detection processes to provide customers with more comprehensive services
.

The production of mRNA vaccines can be divided into two parts
: mRNA stock solution production and mRNA vaccine preparation production.
mRNA stock production is first to design and produce plasmid DNA, linearize it, and then transcribe linear DNA into RNA in vitro through the action of T7 RNA polymerase, further modify RNA by capase, mRNA Cap 2'-O-methyltransferase, etc.
, and finally form mRNA stock solution by purification and ultrafiltration
.
Preparation production is mainly the use of liposomes to encapsulate the mRNA stock solution, followed by finished product filling and quality control to form the final product
.
Relying on its own mRNA raw enzyme advantages, nearshore protein has established a full-process CRO service
from plasmid production to mRNA stock solution production.
In addition, according to the Technical Guidelines for Pharmaceutical Research of mRNA Vaccines for the Prevention of Novel Coronavirus (Trial) issued by the Center for Drug Review of the State Food and Drug Administration (NMPA), and the draft guideline "mRNA Vaccine Quality Analysis Methods" developed by the US Pharmacopoeia (USP), nearshore protein has established and optimized the quality control system of mRNA stock solution to detect key quality attributes, as well as process-related residues and safety
.

Due to the key advantages of mRNA treatment methods in terms of their versatility, adaptability and cost, mRNA therapies are being actively deployed by enterprises in infectious diseases, tumors, rare diseases, autoimmune diseases and other fields, and are reshaping the biomedical landscape
.