Editor's note: this article selected the Sino-Thai Securities Research Institute "mRNA vaccine is which sacred"? The inactivated and attenuated vaccine of Heguo Shell Network has been developed for at least a few years, but it only takes two months for the Chinese Academy of military Sciences and Moderna Inc. "two articles.
According to the latest data from Johns Hopkins University in the United States, as of 8:10 Beijing time on April 9, there were 1.51 million confirmed cases, 88000 deaths and 320000 cured cases of COVID-19 worldwide. With the continuous global spread of the epidemic, the death cases of COVID-19 patients have appeared in the slums of India and backward African areas. their medical conditions are far behind those of developed countries, and now the media do not pay enough attention to them. the backward areas in the next week or two weeks will most likely become the second round of shock waves of the global epidemic, and the global epidemic will face greater challenges in the future. Now everyone is eagerly looking forward to the COVID-19 vaccine to be put on the market as soon as possible.
The adenovirus vaccine of CANSINOBIO of China and the mRNA vaccine of Moderna Inc of the United States are the fastest developed vaccines in the world, both of which entered clinical phase I in mid-March 2020. From the fluctuation of the stock price, CANSINOBIO's stock price seems to go more smoothly, which may also mean that CANSINOBIO's vaccine is more likely to become the world's first COVID-19 vaccine, but it does not mean that CANSINOBIO is the final winner. This article will introduce the mRNA vaccine first, and then compare CANSINOBIO's adenovirus vaccine with Moderna Inc's mRNA vaccine.
1. Definition of mRNA vaccine:
MRNA, called messenger RNA, acts as a bridge between DNA and protein in the genetic process. In that case, mRNA vaccine is a kind of RNA, which corresponds to the mRNA structure of the pathogen (but does not cause disease), which can be delivered to human cells, and then the human body produces antigen proteins, causing specific immune response.
注：
1. DNA exists in the nucleus, but the nucleus can not synthesize proteins. RNA is required to copy the DNA, then come out from the nucleus and enter the cytoplasm to synthesize amino acids, which are arranged to form proteins.
2. Compare the vaccine to a missile against the virus. DNA is the original blueprint for building the missile. RNA is to enable engineers to understand the actual drawings that can guide the factory how to build the missile. Amino acids are individual parts, and proteins are finished missiles.
2. The process of mRNA vaccine functioning:
The main results are as follows: 1) the corresponding mRNA is prepared based on the obtained pathogen antigen sequence, and the step of wrapping mRNA; through various liposome delivery vectors is the core technology of mRNA vaccine development.Synthetic modification(improve the stability of mRNA molecules, prevent degradation) andDelivery systemImprove the efficiency of entering human cells, so that the production of antigens stimulate the human body to produce an immune response.
2) inject it into the human body
3) mRNA releases and expresses antigen proteins in cells, and the human immune system will recognize these specific antigens and stimulate the body to produce immune response.
3. MRNA vaccine technology is compared with other technical routes:
1) traditional vaccines:
Inactivated, attenuated and subunit vaccines. The advantages of inactivated and attenuated vaccine are long-lasting immunity and relatively high yield, but the speed of research and development is slow and the screening is difficult.
2) New vaccine:
Genetically engineered subunit vaccine:The gene sequence of virus surface antigen is directly expressed in organisms. The advantage is that the production process is very mature, safety and stability are very good, but the disadvantage is that it is not suitable for people with low immunity.
Viral vector vaccine:The gene sequence that encodes the antigen protein is loaded into non-pathogenic microorganisms (such as adenoviruses, viruses that can cause colds in most people), and then cause specific immune response.
Nucleic acid vaccines (such as mRNA vaccines):The gene sequence encoding antigen protein and related vectors are combined and delivered directly to the human body to cause specific immune response.
Note: the genetic engineering subunit vaccine is to transfer the virus gene sequence directly into the human body for expression, and the nucleic acid vaccine is to transfer the virus expression protein gene sequence into the human body for expression.
4. Advantages and disadvantages of mRNA vaccine:
1) advantages:
A) short R & D cycle.Moderna IncThe RNA sequence was determined within 3 days, and the first batch of experimental vaccines were produced in 28 days.Because there is no need to synthesize proteins in vitro, the mRNA fragments caused by the virus can be directly injected into human cells by biological means. According to the RNA code of the virus, human cells synthesize the virus protein directly, form the immune response directly, and synthesize the antibody.
B) short production cycle (40 days) and other advantages, low production cost.Because the traditional vaccine requires many steps and the synthesis conditions are very strict, it is difficult to produce in large quantities in a short time. The rapid synthesis of mRNA vaccine is possible because it saves many intermediate processes.
C) long immune response time
2) disadvantages:
a）It is very important to choose which piece of genetic information to synthesize mRNA vaccine according to the genetic code of the virus.Because unlike traditional vaccines with actual viruses as a reference, relying on genetic knowledge of biology to predict / design mRNA vaccines is a bit like "working behind closed doors".
b）MRNA is not as stable as protein or DNA, and it is very difficult to preserve, especially after entering the human body, how to avoid the body's own immune system, how not to be eliminated by the immune system as a foreign pathogen, is a difficult problem.
COVID-19 Vaccine-adenovirus Vaccine and mRNA Vaccine Race:
1) CANSINOBIO's adenovirus vaccine:
CANSINOBIO and Chen Wei, academician of the Institute of military Medicine of the Academy of military Sciences, jointly developed the recombinant novel coronavirus vaccine (Adenovirus vector), has passed the clinical research registration review, has been approved to enter the phase I clinical trial on March 19, 2020, and 108 volunteers have been vaccinated. In addition, Academician Chen Wei also used this technology to successfully develop an Ebola vaccine in 2019.
Advantages:
A) High certainty:
Because of the maturity of adenovirus vector technology, it is possible for adenoviruses to enter human cells with novel coronavirus's special pathogenic antigen to synthesize antibodies against novel coronavirus. SoIn terms of overcoming the scavenging effect of the body's immune system, adenovirus vaccines are more likely to enter human cells than mRNA vaccines alone.
B) low side effects:
In addition, the coronavirus has been used for a variety of biomedical purposes, and the technology is relatively mature, so the vaccine developed by China has been able to complete the design, laboratory testing and initial animal experiments in such a short period of time. And quickly enter the clinical trial phase. According to public information, the initial animal experiments of the vaccine showed good immunostimulatory ability, and no obvious side effects were found.
Disadvantages:
A) Antibodies may not be produced.Most people already have a large number of adenovirus antibodies (such as the common cold, adenovirus is one of its pathogens), so after adenovirus is injected into the human body, it is likely to be eliminated by the immune system. COVID-19 antibody will not be produced at all.
B) whether the antibody is sufficient.Some professional studies have reported that adenoviruses have some serious and even long-term side effects when they are used as vaccine vectors or tumor treatments.
2) Moderna Inc's mRNA vaccine:
Moderna Inc是RNADrug and vaccine research and development of unicorn enterprises, technology accumulation is relatively profound, COVID-19 vaccine research and development progress is rapid. Moderna Inc was founded in 2010, has always been with RNA technology as the core, is a leading enterprise in the industry, has reached cooperation with AstraZeneca PLC, Merck, Vertex, Alexion and other companies.
After the emergence of the COVID-19 epidemic, the company actively carried out vaccine research and development.The RNA sequence was determined within 3 days, the first batch of experimental vaccines were produced in 28 days, and the phase I clinical phase was announced on March 16.
The advantages of Moderna Inc：
A) short R & D cycle.The RNA sequence was determined within Moderna3 days, and the first batch of experimental vaccines were produced in 28 days.
B) advantages such as short production cycle (40 days) and low production cost
C) long immune response time
Moderna Inc's shortcomings：
a）Moderna Inc's clinical trial took a long time.At present, there is no mRNA product, so the overall safety observation period of Moderna Inc is expected to be 394days, which will be completed later than CANSINOBIO.I Stage clinical
b）Moderna IncSafety remains to be seen.
Summary:
At present, CANSINOBIO's adenovirus vaccine and Moderna Inc's COVID-19 mRNA vaccine are in clinical phase I. If the competition is in the clinical stage, who can become the first COVID-19 vaccine pharmaceutical company, then it is likely to be CANSINOBIO's adenovirus vaccine.
In the future, if the COVID-19 vaccines of CANSINOBIO and Moderna Inc can be successfully put on the market, and novel coronavirus exists for a long time like the global hepatitis B virus, then Moderna Inc can rely on its advantages such as low production cycle and low cost. Become the final winner. In addition, if Moderna Inc's mRNA vaccine is successfully marketed, it will become an epoch-making product in the vaccine field.
Edit / elisa